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Background: Standard approaches to the treatment of chronic post-radiation proctitis are associated with a high risk of complications and a high percentage of unsatisfactory results due to the reduced regenerative potential of irradiated tissues. Regenerative surgery techniques using the stromal-vascular cell fraction (SVF) based on the patient's autologous adipose tissue are a promising direction for study., Clinical Case Description: A 76-year-old patient suffering from chronic post-radiation erosive-ulcerative proctitis, grade 4 according to RTOG-EORTC, complicated by recurrent profuse rectal bleeding, underwent local autotransplantation of SVF into the submucosal layer of the rectum and pararectal connective tissue. The follow-up colonoscopies 1 and 6 months after the surgery and histological examination showed the complete epithelialization of ulcerative defects and a decrease in proctitis activity. There were no bleeding episodes during the 12-month postoperative observation period., Conclusion: The proangiogenic, wound-healing, and anti-apoptotic effects of the SVF cell suspension provided reduction of inflammation activity, epithelialization of ulcers, and elimination of defecation-associated hemorrhage, following the SVF injection into the submucosal layer of the rectal wall and pararectal connective tissue in a patient with post-radiation proctitis with ulcers and recurrent bleeding., (© 2024. The Author(s).)

Decellularized extracellular matrix (dECM) hydrogels loaded with adipose-derived stromal cells (ASC) or their conditioned medium (ASC CM) present a promising and versatile treatment approach for tissue vascularization and regeneration. These hydrogels are easy to produce, store, personalize, manipulate, and deliver to the target tissue. This literature review aimed to investigate the applications of dECM hydrogels with ASC or ASC CM for in vivo tissue vascularization. Fourteen experimental studies have been reviewed using vessel density as the primary outcome parameter for in vivo vascularization. The studies consistently reported an increased efficacy in augmenting angiogenesis by the ASC or ASC CM-loaded hydrogels compared to untreated controls. However, this systematic review shows the need to standardize procedures and characterization, particularly of the final administered product(s). The findings from these experimental studies highlight the potential of dECM hydrogel with ASC or ASC CM in novel tissue regeneration and regenerative medicine applications., Competing Interests: Declaration of competing interest The authors declare no conflict of interest. The funders had no role in the study's design, in the collection, analyses, interpretation of data, or the writing of the manuscript., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)

This study investigated the effects of transplanted testicular stromal stem cells (tSSCs) on surgically damaged testis tissue. Ten-week-old male Wistar albino rats were divided into three groups: control (n = 6), damage (DG) (n = 6) and testicular stromal stem cell (TSSC) (n = 6) groups. Surgically induced damage was inflicted on the left testes of both the DG and TSSC groups, with no intervention on the right testes. In the TSSC group, damaged testes were treated with transplanted tSSCs, followed by orchiectomy after 15 days. Testes tissues were stained with haematoxylin-eosin (H&E), and recovery rates of functional structures were assessed by modified Johnsen scoring. The effects of tSSCs on testicular tissue were demonstrated by immunohistochemistry using BAX, BCL-2 and caspase 3. Serum testosterone levels were analysed using the enzyme-linked immunosorbent assay (ELISA) method. Surgical damage caused germ cell degeneration in some seminiferous tubules and a decrease in interstitial areas. With tSSC treatment, improvements in testicular architecture were identified through spermatogenesis in the seminiferous tubules and normal histological structures in the interstitial areas. Correspondingly, in the modified Johnsen score, the DG group showed a significant difference compared to the other groups (p = 0.001). High expressions of BAX, BCL-2 and caspase-3 in the DG group revealed prominent features of apoptosis. With the injection of tSSCs, these expressions significantly normalized according to H score analysis (all p = 0.004). Although serum testosterone levels in the tSSC group were higher compared to the control and DG groups, this difference was not statistically significant (p = 0.119). This study suggests transplanting tSSCs could accelerate tissue healing after testicular sperm extraction (TESE) surgery for azoospermia patients, potentially paving the way for a new and important clinical treatment., (© 2024 Wiley‐VCH GmbH. Published by John Wiley & Sons Ltd.)

Objective: Our aim was to assess the effectiveness of stromal vascular fraction (SVF) in treating scars using the latest meta-analysis., Methods: We used PubMed, Embase, Cochrane, and Web of Science to search the studies used to evaluate the efficacy of SVF in scar treatment. At least one of the following outcome measures were reported: vascularity, pigmentation, thickness, relief, pliability, surface area, pain, itching and color., Results: A total of four eligible articles comprising 145 patients (64 SVF patients and 81 non-SVF patients) were included. The findings of this meta-analysis indicated that SVF had significant therapeutic effects in terms of vascularity (SMD/MD, 95% CI: -1.12, -0.02; p = 0.04), itching (SMD/MD, 95% CI: -0.61, -0.13; p = 0.002), POSAS (SMD/MD, 95% CI: -5.93, -1.47; p = 0.001), and thickness (SMD/MD, 95% CI: -1.04, -0.35; p < 0.001). In terms of OSAS (SMD/MD, 95% CI: -9.14, 0.59; p = 0.09), pigmentation (SMD/MD, 95% CI: -1.02, 0.06; p = 0.08), relief (SMD/MD, 95% CI: -1.14, 0.16; p = 0.14), surface area (SMD/MD, 95% CI: -0.91, 0.26; p = 0.27), PSAS (SMD/MD, 95% CI: -7.20, 0.49; p = 0.09), pain (SMD/MD, 95% CI: -0.87, 0.07; p = 0.10), pliability (SMD/MD, 95% CI: -0.57, 0.01; p = 0.06), and color (SMD/MD, 95% CI: -1.78, 0.48; p = 0.26), there were no significant statistical differences., Conclusion: In view of the heterogeneity and potential selective bias, further large-scale, prospective, and multicenter clinical trials are needed to confirm the efficacy and reliability of SVF in the treatment of scars., (© 2024 The Author(s). Skin Research and Technology published by John Wiley & Sons Ltd.)

Purpose: This study aims to investigate the potential of stromal vascular fraction (SVF) for peripheral nerve regeneration., Methods: A scoping review of Scopus and PubMed databases was conducted. Inclusion criteria were human or animal studies exploring the use of SVF for peripheral nerve regeneration. Studies were categorized by assessed outcomes: pain assessment, neural integrity, muscle recovery, and functional recovery. Level of evidence and study quality were assessed., Results: Nine studies met the inclusion criteria. SVF injection in humans with trigeminal neuropathic pain reduced pain scores from 7.5 ± 1.58 to 4.3 ± 3.28. SVF injection improved sensation in humans with leprosy neuropathy. Repairing transected rat sciatic nerves with SVF-coated nerve autografts improved wet muscle weight ratios (0.65 ± 0.11 vs 0.55 ± 0.06) and sciatic functional index (SFI) scores (-68.2 ± 9.2 vs -72.5 ± 8.9). Repairing transected rat sciatic nerves with SVF-coated conduits increased the ratio of gastrocnemius muscle weights (RGMW) (7-10% improvement), myelinated fibers (1,605 ± 806.2 vs 543.6 ± 478.66), and myelin thickness (5-20% increase). Repairing transected rat facial nerves with SVF-coated conduits improved whisker motion (9.22° ± 0.65° vs 1.90° ± 0.84°) and myelin thickness (0.57 μm ± 0.17 vs 0.45 μm ± 0.14 μm). Repairing transected rat sciatic nerves with SVF-coated nerve allografts improved RGMW (85 vs 50%), SFI scores (-20 to -10 vs -40 to -30), and Basso, Beatie, and Bresnahan locomotor scores (18 vs 15). All metrics mentioned above were statistically significant. The human studies were level 4 evidence due to being case series, while animal studies were the lowest level of evidence., Conclusion: Despite initial promising results, the low-level evidence from the included studies warrants further investigation., (Copyright © 2024 American Association of Oral and Maxillofacial Surgeons. Published by Elsevier Inc. All rights reserved.)

Background: Intrauterine adhesion (IUA) as a prevalent gynecological disease is developed from infection or trauma. However, therapeutic strategies to repair damaged endometrium are relatively limited. Emerging studies have shed light on the crucial role of endometrial stromal cells (EnSCs) in the process of uterine endometrial regeneration. EnSCs isolated from the uterine endometrium have similar characteristics to mesenchymal stem cells (MSCs). However, it is still unknown whether EnSCs could be used as donor cells to treat IUA. The aim of this study was to evaluate the potential efficacy of EnSCs in treating rat IUA., Methods: Human EnSCs were isolated from the endometrial tissue of healthy female donors and subjected to extensive expansion and culture in vitro. Immunofluorescence, flow cytometry, cell proliferation assay, trilineage differentiation experiment, and decidualization assay were used to characterize the biological properties of EnSCs. We evaluated the immunoregulatory potential of EnSCs by analyzing their secreted cytokines and conducting bulk RNA sequencing after IFN-γ treatment. After EnSCs were transplanted into the uterine muscle layer in IUA rats, their therapeutic effects and underlying mechanisms were analyzed using histological analysis, Q-PCR, fertility and pregnancy outcome assay, and transcriptome analysis., Results: We successfully isolated EnSCs from the endometrium of human donors and largely expanded in vitro. EnSCs exhibited characteristics of mesenchymal stem cells and retained responsiveness to sex hormones. Following IFN-γ stimulation, EnSCs upregulated the anti-inflammatory cytokines and activated immunosuppressive molecules. Xenogeneic transplantation of EnSCs successfully repaired injured endometrium and significantly restored the pregnancy rate in IUA rats. Mechanistically, the therapeutic effects of EnSCs on IUA endometrium functioned through anti-inflammation, anti-fibrosis and the secretion of regeneration factor., Conclusions: Due to their large expansion ability, immunoregulatory properties, and great potential in treating IUA, EnSCs, as a valuable source of donor cells, could offer a potential treatment avenue for injury-induced IUA., (© 2024. The Author(s).)

Thin endometrium (TE), which mainly occurs as a result of severe damage to the endometrial basalis, is one of the prominent etiologies of menstrual abnormalities, infertility, and recurrent miscarriage in women. Previous studies have demonstrated that mesenchymal stem cells (MSCs) are considered ideal cells with multipotency for regenerative medicine and exhibit therapeutic effects on TE through their cellular secretions. However, there is limited research on strategies to enhance MSC secretion to improve their therapeutic efficacy. Herein, we isolated menstrual blood-derived mesenchymal stem cells (MenSCs) from menstruation and transformed them into decidualized stromal cells (DSCs), which are specialized cells with enhanced secretory functions. To assess the therapeutic potential of DSCs compared to MenSCs, we conducted a series of experiments in cells and animals. The results demonstrated that DSCs exhibited changes in morphology compared to MenSCs, with a decrease in cell proliferation but a significant improvement in secretion function. Furthermore, DSCs facilitated the restoration of endometrial thickness and increased the number of glands and blood vessel formation. Most importantly, the pregnancy rates in rats were effectively restored, bringing them closer to normal levels. These findings greatly contribute to our understanding of stem cell therapy for TE and strongly suggest that DSCs could hold significant promise as a potential treatment option for TE., (© 2024. The Author(s).)

Objective: This study aimed to investigate the effect of human adipose tissue derived stromal vascular fraction (AD-SVF) and mesenchymal stem cells (AD-MSCs) on blood flow recovery and neovascularisation in a rat hindlimb ischaemia model., Methods: SVF was isolated using an automated centrifugal system, and AD-MSCs were obtained from adherent cultures of SVF cells. Rats were divided into four groups of six rats each: non-ischaemia (Group 1); saline treated ischaemia (Group 2); SVF treated ischaemia (Group 3); and AD-MSC treated ischaemia (Group 4). Unilateral hindlimb ischaemia was induced in Sprague-Dawley rats via femoral artery ligation. Saline, SVF, or AD-MSCs were injected intramuscularly into the adductor muscle intra-operatively. Cell viability was calculated as the percentage of live cells relative to total cell number. Blood flow improvement, muscle fibre injury, and angiogenic properties were validated using thermal imaging and histological assessment., Results: The viabilities of SVF and AD-MSCs were 83.3% and 96.7%, respectively. Group 1 exhibited no significant temperature difference between hindlimbs, indicating a lack of blood flow changes. The temperature gradient gradually decreased in SVF and AD-MSC treated rats compared with saline treated rats. In addition, only normal muscle fibres with peripherally located nuclei were observed in Group 1. Groups 3 and 4 exhibited significantly fewer centrally located nuclei, indicating less muscle damage compared with Group 2. Regarding angiogenic properties, CD31 staining of endothelial cells showed similar patterns among all groups, whereas expression of vascular endothelial growth factor, as a crucial angiogenesis factor, was enhanced in the SVF and AD-MSC treated groups., Conclusion: SVF and AD-MSCs improved blood flow and neovascularisation in a rat hindlimb ischaemia model, suggesting their potential ability to promote angiogenesis. Further extensive research is warranted to explore their potential applications in the treatment of severe lower extremity arterial disease., (Copyright © 2023. Published by Elsevier B.V.)

Background: Although previous clinical studies have reported that cell-assisted lipotransfer increases the fat survival rate in facial fat transplants, most were case studies without quantitative evaluation. A multicenter randomized controlled study was performed to evaluate the safety and efficacy of the stromal vascular fraction (SVF) in facial fat grafts., Methods: Twenty-three participants were enrolled for autologous fat transfer in the face, and assigned randomly to the experimental ( n = 11) or control ( n = 12) group. Fat survival was assessed using magnetic resonance imaging at 6 and 24 weeks postoperatively. Subjective evaluations were performed by the patients and surgeons. To address safety concerns, results of an SVF culture and the postoperative complications were recorded., Results: The overall fat survival rate was significantly higher in the experimental group than in the control group (6 weeks, 74.5% ± 9.99% versus 66.55% ± 13.77%, P < 0.025; 24 weeks, 71.27% ± 10.43% versus 61.98% ± 13.46%, P < 0.012). Specifically, graft survival in the forehead was 12.82% higher in the experimental group when compared with that in the control group at 6 weeks ( P < 0.023). Furthermore, graft survival in the forehead ( P < 0.021) and cheeks ( P < 0.035) was superior in the experimental group at 24 weeks. At 24 weeks, the aesthetic scores given by the surgeons were higher in the experimental group than in the control group ( P < 0.03); however, no significant intergroup differences were noted in the patient-evaluated scores. Neither bacterial growth from SVF cultures nor postoperative complications were noted., Conclusion: SVF enrichment for autologous fat grafting can be a safe and effective technique for increasing the fat retention rate., Clinical Question/level of Evidence: Therapeutic, II., (Copyright © 2023 by the American Society of Plastic Surgeons.)

Encapsulating multiple growth factors within a scaffold enhances the regenerative capacity of engineered bone grafts through their localization and controls the spatiotemporal release profile. In this study, we bioprinted hybrid bone grafts with an inherent built-in controlled growth factor delivery system, which would contribute to vascularized bone formation using a single stem cell source, human adipose-derived stem/stromal cells (ASCs) in vitro. The strategy was to provide precise control over the ASC-derived osteogenesis and angiogenesis at certain regions of the graft through the activity of spatially positioned microencapsulated BMP-2 and VEGF within the osteogenic and angiogenic bioink during bioprinting. The 3D-bioprinted vascularized bone grafts were cultured in a perfusion bioreactor. Results proved localized expression of osteopontin and CD31 by the ASCs, which was made possible through the localized delivery activity of the built-in delivery system. In conclusion, this approach provided a methodology for generating off-the-shelf constructs for vascularized bone regeneration and has the potential to enable single-step, in situ bioprinting procedures for creating vascularized bone implants when applied to bone defects.

Background: Cell-assisted lipotransfer, a fat graft mixed with adipose-derived stromal cells, is known to enhance fat graft retention. Previously, the authors showed that intravenous injection of adipose-derived stromal cells can improve the survival of grafted fat. In the present study, the authors investigated the effects of a secondary intravenous injection of adipose-derived stromal cells on fat grafting., Methods: Wild-type C57BL/6J (B6) mice were used as donors for grafted fat and as recipients. Adipose-derived stromal cells were harvested from green fluorescent protein and DsRed B6 mice. The recipient mice were divided into three groups: SI ( n = 10), RI1 ( n = 10), and RI2 ( n = 11). All groups received intravenous injections of green fluorescent protein adipose-derived stromal cells immediately after fat grafting. The RI1 and RI2 groups received repeated intravenous injections of DsRed adipose-derived stromal cells at 1 and 2 weeks, respectively, after fat grafting. The grafted fat volume was measured using micro-computed tomography., Results: Secondarily injected DsRed adipose-derived stromal cells were recruited to the grafted fat and resulted in a higher retention of graft volume and vascular density ( P < 0.05). The stromal-derived factor-1 and C-X-C chemokine receptor type 4 genes related to stem cell homing were highly expressed in the grafted fat and adipose-derived stromal cells ( P < 0.05). The RI2 group showed a higher graft volume and vascular density than the SI and RI1 groups ( P < 0.05)., Conclusions: A secondary intravenous injection of adipose-derived stromal cells at a 2-week interval enhances the effect of adipose-derived stromal cell enrichment in fat grafting. These findings refine clinical protocols and enhance the therapeutic value of cell-assisted lipotransfer., Clinical Relevance Statement: In a modified animal model of cell-assisted lipotransfer, the authors demonstrated that secondary intravenous administration of adipose-derived stromal cells improved retention of grafted fat., (Copyright © 2023 by the American Society of Plastic Surgeons.)

Background: Stromal vascular fraction (SVF) and fat grafting are emerging alternatives to implants for breast augmentation. However, the lack of controlled clinical data has led to conflicting results regarding the effectiveness of surgical treatments. This study aimed to identify the key factors affecting the outcomes of fat grafting with SVF and to recognize novel methods to improve the retention rate., Patients and Methods: In total, 384 women underwent breast augmentation using fat grafting with SVF. The patients were preoperatively and postoperatively managed and recalled for follow-up at 3, 6, and 18 months., Results: The average volume of the injection in the left breast was 162.35 mL (range, 50-260 mL). The postoperative retention rates were 78.65% in 384 patients at 3 months, 77.17% in 273 patients at 6 months, and 77.48% in 102 patients at 18 months. The retention rates were compared based on the number of SVF cells; patients with more than 60 million cells had a retention rate of 70.77%, and those with less than 60 million cells had a retention rate of 85.60% at 18 months. The retention rates at the 18-month follow-up were 65.62% and 85.09% in stiff and soft breasts, respectively. A higher number of cells in the SVF was associated with a greater retention volume, and the retention volume was greater in patients with soft breasts.Given the higher use of the right arm, after 18 months of the surgery, the retention rate of the right breast (60.35%) was lower than that of the left breast (77.48%) ( P < 0.05; t = -13.199)., Conclusions: Limiting arm movement, increasing the number of cells in the SVF, and improving the skin tension might enhance the retention rate in patients undergoing breast augmentation., Competing Interests: Conflicts of Interest and Source of Funding: None declared., (Copyright © 2023 Wolters Kluwer Health, Inc. All rights reserved.)

Background: For decades, facial fat grafting has been used in clinical practice for volume restoration. The main challenge of this technique is variable volume retention. The addition of supplements to augment fat grafts and increase volume retention has been reported in recent years., Objectives: The aim of this systematic review was to investigate which supplements increase volume retention in facial fat grafting as assessed by volumetric outcomes and patient satisfaction., Methods: Embase, Medline, Ovid, Web of Science Core Collection, Cochrane Central Register of Controlled Trials, and Google Scholar were searched up to November 30, 2020. Only studies assessing volume after facial fat grafting with supplementation in human subjects were included. Outcomes of interest were volume or patient satisfaction. The quality of the studies was assessed with the Effective Public Health Practice Project tool., Results: After duplicates were removed 3724 studies were screened by title and abstract. After reading 95 full-text articles, 27 studies were eligible and included for comparison. Supplementation comprised of platelet-rich plasma, platelet-rich fibrin, adipose tissue-derived stromal cells or bone marrow-derived stromal cells, cellular or tissue stromal vascular fraction, or nanofat. In 13 out of 22 studies the supplemented group showed improved volumetric retention and 5 out of 16 studies showed greater satisfaction. The scientific quality of the studies was rated as weak for 20 of 27 studies, moderate for 6 of 27 studies, and strong for 1 study., Conclusions: It remains unclear if additives contribute to facial fat graft retention and there is a need to standardize methodology., (© 2022 The Aesthetic Society.)

Background: The main challenge with fat grafting is loss of some of the graft to postsurgery resorption. Previous studies suggest that adipose-derived stromal cells (ASCs) can improve the volume retention of fat grafts but there is a lack of randomized trials to support the use of ASCs in clinical practice., Objectives: This trial aimed to investigate whether ASCs improve fat graft volume retention in patients undergoing breast augmentation with lipofilling., Methods: This was a double-blind, randomized controlled trial of breast augmentation with ASC-enriched fat grafting. Healthy women aged 30 to 45 years were enrolled. First, the participants underwent liposuction to obtain fat for culture expansion of ASCs. Then, the participants were randomly assigned to undergo a 300- to 350-mL breast augmentation with ASC-enriched fat grafting (10 × 106 ASCs/mL fat graft) to 1 of their breasts and placebo-enriched fat grafting of identical volume to the contralateral breast. The primary outcome was fat graft volume retention after a 1-year follow-up measured with MRI. The trial is registered at www.clinicaltrialsregister.eu (EudraCT-2014-000510-59)., Results: Ten participants were included in the trial; all completed the treatment and follow-up. No serious adverse events occurred. Fat graft volume retention after 1 year was 54.0% (95% CI, 30.4%-77.6%) in the breasts treated with ASC-enriched fat grafting (n = 10) and 55.9% (95% CI, 28.9%-82.9%) in the contralateral breasts treated with placebo-enriched fat grafting (n = 10) (P = 0.566)., Conclusions: The findings of this trial do not support that ASC-enriched fat grafting is superior to standard fat grafting for breast augmentation., (© The Author(s) 2022. Published by Oxford University Press on behalf of The Aesthetic Society. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Background: A paracrine mechanism is thought to mediate the proangiogenic capacity of adipose-derived stromal/stem cells (ASCs). However, the precise mechanism by which ASCs promote the formation of blood vessels by endothelial progenitor cells (EPCs) is unclear., Methods: The EPCs-ASCs cocultures prepared in different ratios were subjected to tube formations assay to verify whether ASCs could directly participate in the tube genesis. The supernatant from cultured ASCs was used to stimulate EPCs to evaluate the effects on the angiogenic property of EPCs, as well as capacity for migration and invasion. A coculture model with transwell chamber were used to explore the regulation of angiogenesis markers expression in EPCs by ASCs. We then mixed ASCs with EPCs and transplanted them with adipose tissue into nude mice to evaluate the effects on angiogenesis in adipose tissue grafts., Results: In the EPCs-ASCs cocultures, the tube formation was significantly decreased as the relative abundance of ASCs increased, while the ASCs was found to migrate and integrated into the agglomerates formed by EPCs. The supernatant from ASCs cultures promoted the migration and invasion of EPCs and the ability to form capillary-like structures. The expression of multiple angiogenesis markers in EPCs were significantly increased when cocultured with ASCs. In vivo, ASCs combined with EPC promoted vascularization in the fat transplant. Immunofluorescence straining of Edu and CD31 indicated that the Edu labeled EPC did not directly participate in the vascularization inside the fat tissue., Conclusions: ADSC can participate in the tube formation of EPC although it cannot form canonical capillary structures. Meanwhile, Soluble factors secreted by ASCs promotes the angiogenic potential of EPCs. ASCs paracrine signaling appears to promote angiogenesis by increasing the migration and invasion of EPCs and simultaneously upregulating the expression of angiogenesis markers in EPCs. The results of in vivo experiments showed that ASCs combined with EPCs significantly promote the formation of blood vessels in the fat implant. Remarkably, EPCs may promote angiogenesis by paracrine regulation of endogenous endothelial cells (ECs) rather than direct participation in the formation of blood vessels., Competing Interests: The authors have declared that no competing interests exist.

Acute respiratory distress syndrome (ARDS) is the most common cause of death in COVID-19 patients. The cytokine storm is the main driver of the severity and magnitude of ARDS. Placenta-derived decidua stromal cells (DSCs) have a stronger immunosuppressive effect than other sources of mesenchymal stromal cells. Safety and efficacy study included 10 patients with a median age of 50 (range 14-68) years with COVID-19-induced ARDS. DSCs were administered 1-2 times at a dose of 1 × 10 6 /kg. End points were safety and efficacy by survival, oxygenation and effects on levels of cytokines. Oxygenation levels increased from a median of 80.5% (range 69-88) to 95% (range 78-99) (p = 0.012), and pulmonary infiltrates disappeared in all patients. Levels of IL-6 decreased from a median of 69.3 (range 35.0-253.4) to 11 (range 4.0-38.3) pg/ml (p = 0.018), and CRP decreased from 69 (range 5-169) to 6 (range 2-31) mg/ml (p = 0.028). Two patients died, one of a myocardial infarction and the other of multiple organ failure, diagnosed before the DSC therapy. The other patients recovered and left the intensive care unit (ICU) within a median of 6 (range 3-12) days. DSC therapy is safe and capable of improving oxygenation, decreasing inflammatory cytokine level and clearing pulmonary infiltrates in patients with COVID-19., (© 2021 The Authors. Journal of Cellular and Molecular Medicine published by Foundation for Cellular and Molecular Medicine and John Wiley & Sons Ltd.)

In patients with localized scleroderma (LoS), facial deformity induced by subcutaneous atrophy greatly reduces life quality. Autologous fat grafting (AFG) is used for volume restoration but with low-fat retention due to various reasons. Adipose-derived stem cells (ADSCs) have shown potential effects in improving fat retention. We aimed to compare the feasibility and efficacy of improving fat retention in LoS patients among the ADSCs-assisted, the stromal vascular fraction (SVF)-assisted and conventional AFG methods. A pilot study with a 6-month follow-up among 18 LoS patients was conducted. Participants were randomly assigned into three AFG groups: conventional group, SVF-assisted group, and ADSCs-assisted group. The SVF-assisted group received SVF-assisted AFG at the SVF:fat ratio of 1:1. The ADSCs-assisted group received the mixture of ADSCs-enriched fat graft supplemented with 5 × 10 5 ADSCs/mL fat. Volume retention was measured by magnetic resonance imaging, and clinical photographs were taken for outcome evaluation. At sixth-month follow-up, the fat retention of ADSCs-assisted group was 49.83 ± 3.61%, significantly higher than 31.75 ± 1.73% of SVF-assisted group (P = .0004), and 21.86 ± 1.68% of the conventional group (P < .0001). A significant difference of the fat retention was also observed between the SVF-assisted and conventional group (P = .0346). No severe adverse events occurred during the procedure and follow-up. This pilot study suggests that ADSCs-assisted AFG is a safe, feasible, and attractive alternative to conventional and SVF-assisted AFG in the correction of facial atrophy of LoS patients. Future studies with large patient samples are needed for confirmation. (Chinese Clinical Trial Registry, ChiCTR1900025717)., (© 2021 The Authors. STEM CELLS TRANSLATIONAL MEDICINE published by Wiley Periodicals LLC on behalf of AlphaMed Press.)

The intraoperative ischemia in partial nephrectomy (PN) often leads to postoperative renal function impairment and fibrosis, which can be regulated by macrophage polarization. We have previously demonstrated that microvesicles derived from human Wharton's Jelly mesenchymal stromal cells (hWJMSC-MVs) attenuated renal ischemia-induced renal fibrosis and contained a substantial quantity of hepatocyte growth factor (HGF). Herein, we investigated whether MSC-MVs regulate macrophage polarization and ameliorate renal fibrosis following ischemia-PN via transferring HGF. A rat model of ischemia-PN was established by 45 min of left renal ischemia followed by removal of 1/3 upper left kidney. MSC-MVs were injected through the tail vein immediately after ischemia. Renal injury biomarkers were measured and histologic analysis was performed to analyze renal injury. A co-culture model of THP-1 macrophages and MSC-MVs was utilized. The expression of M1 markers and M2 markers were determined to evaluate macrophage polarization. MSC-MV administration significantly ameliorated renal inflammation, lesions, and fibrosis in ischemia-PN rats, and promoted M2 macrophage polarization both in rat remnant renal tissues and LPS-treated THP-1 cells. These effects of MSC-MVs were compromised when HGF expression was downregulated in MSC-MVs. Collectively, MSC-MVs promote M2 macrophage polarization and attenuate renal fibrosis following ischemia-PN via transferring HGF.

Cochlear implants are considered the gold standard therapy for subjects with severe hearing loss and deafness. Cochlear implants bypass the damaged hair cells and directly stimulate spiral ganglion neurons (SGNs) of the auditory nerve. Hence, the presence of functional SGNs is crucial for speech perception in electric hearing with a cochlear implant. In deaf individuals, SGNs progressively degenerate due to the lack of neurotrophic support, normally provided by sensory cells of the inner ear. Adipose-derived stromal cells (ASCs) are known to produce neurotrophic factors. In a guinea pig model of sensory hearing loss and cochlear implantation, ASCs were autologously transplanted into the scala tympani prior to insertion of a cochlear implant on one side. Electrically evoked auditory brain stem responses (eABR) were recorded 8 weeks after cochlear implantation. At conclusion of the experiment, the cochleae were histologically evaluated. Compared to untreated control animals, transplantation of ASCs resulted in an increased number of SGNs and their peripheral neurites. In ASC-transplanted animals, mean eABR thresholds were lower and suprathreshold amplitudes larger, suggesting a larger population of intact auditory nerve fibers. Moreover, when compared to controls, amplitude-level functions of eABRs in ASC transplanted animals demonstrated steeper slopes in response to increasing interphase gaps (IPGs), indicative of better functionality of the auditory nerve. In summary, results suggest that transplantation of autologous ASCs into the deaf inner ear may have protective effects on the survival of SGNs and their peripheral processes and may thus contribute to long-term benefits in speech discrimination performance in cochlear implant subjects., (Copyright © 2021 Wolters Kluwer Health, Inc. All rights reserved.)

Previously, we developed a novel, needle-free waterjet (WJ) technology capable of injecting viable cells by visual guided cystoscopy in the urethral sphincter. In the present study, we aimed to investigate the effect of WJ technology on cell viability, surface markers, differentiation and attachment capabilities, and biomechanical features. Porcine adipose tissue-derived stromal cells (pADSCs) were isolated, expanded, and injected by WJ technology. Cell attachment assays were employed to investigate cell-matrix interactions. Cell surface molecules were analyzed by flow cytometry. Cells injected by Williams Needle (WN), normal cannula, or not injected cells served as controls. Biomechanical properties were assessed by atomic force microscopy (AFM). pADSCs injected by the WJ were viable (85.9%), proliferated well, and maintained their in vitro adipogenic and osteogenic differentiation capacities. The attachment of pADSCs was not affected by WJ injection and no major changes were noted for cell surface markers. AFM measurements yielded a significant reduction of cellular stiffness after WJ injections ( p < 0.001). WJ cell delivery satisfies several key considerations required in a clinical context, including the fast, simple, and reproducible delivery of viable cells. However, the optimization of the WJ device may be necessary to further reduce the effects on the biomechanical properties of cells.

Objectives: To investigate the therapy of stress urinary incontinence in a preclinical setting cells were injected into the urethrae of minipigs; however, cells injected by William's needle were frequently misplaced or lost; thus, we investigated if needle-free cell injections using a novel waterjet technology facilitates precise injections in the urethral sphincter complex., Materials and Methods: Porcine adipose tissue-derived stromal cells (pADSCs) were isolated from boars, expanded, labelled, and injected in the sphincter of female pigs by waterjet employing two different protocols. After incubation for 15 min or 3 days, the urethrae of the pigs were examined. Injected cells were visualised by imaging and fluorescence microscopy of tissue sections. DNA of injected male cells was verified by polymerase chain reaction (PCR) of the sex-determining region (SRY) gene. Cell injections by William's needle served as controls., Results: The new waterjet technology delivered pADSCs faster and with better on-site precision than the needle injections. Bleeding during or after waterjet injection or other adverse effects, such as swelling or urinary retention, were not observed. Morphologically intact pADSCs were detected in the urethrae of all pigs treated by waterjet. SRY-PCR of chromosomal DNA and detection of recombinant green fluorescent protein verified the injection of viable cells. In contrast, three of four pigs injected by William's needle displayed no or misplaced cells., Conclusion: Transurethral injection of viable pADSCs by waterjet is a simple, fast, precise, and yet gentle new technology. This is the first proof-of-principle concept study providing evidence that a waterjet injects intact cells exactly in the tissue targeted in a preclinical in vivo situation. To further explore the clinical potential of the waterjet technology longer follow-up, as well as incontinence models have to be studied., (© 2020 The Authors BJU International published by John Wiley & Sons Ltd on behalf of BJU International.)

Background: Fat graft ischemia impedes us from having satisfying long-term results. The quality and quantity culture is a 1-week cell culture that increases the vasculogenic potential of peripheral blood mononuclear cells (PBMNC). This in vivo murine model investigates whether enrichment with quality and quantity-cultured human mononuclear cells (MNC-QQ) improves the vascularization in the human fat graft and whether this decreases the tissue loss., Methods: Human adipose tissue, PBMNC, MNC-QQ, and stromal vascular fraction were prepared. First, PBMNC, MNC-QQ, and stromal vascular fraction were compared in vitro for vasculogenic potential by endothelial progenitor cell colony-forming and culture assays. Second, 0.25-g fat grafts were created with 1 × 106 PBMNC (n = 16), 1 × 106 MNC-QQ (n = 16), 1 × 106 stromal vascular fraction (n = 16), or phosphate-buffered saline as control (n = 16) before grafting in BALB/c nude mice. Grafts were analyzed for weight persistence, vessel formation by CD31 immunohistochemistry, and angiogenic markers by quantitative polymerase chain reaction., Results: MNC-QQ develop more definitive endothelial progenitor cell colonies and more functional endothelial progenitor cells compared to PBMNC and stromal vascular fraction. Weight persistence after 7 weeks was significantly higher in grafts with MNC-QQ (89.8 ± 3.5 percent) or stromal vascular fraction (90.1 ± 4.2 percent) compared with control (70.4 ± 6.3 percent; p < 0.05). MNC-QQ-enriched grafts had the highest vessel density (96.6 ± 6.5 vessels/mm2; control, 70.4 ± 5.6 vessels/mm2; p < 0.05). MNC-QQ exerted a direct vasculogenic effect through vascular integration and a potential paracrine vascular endothelial growth factor-mediated effect., Conclusion: Quality and quantity-cultured human mononuclear cells containing endothelial progenitor cells stimulate fat graft vascularization and enhance graft survival in a rodent recipient., (Copyright © 2020 by the American Society of Plastic Surgeons.)

In cases of lower rectum-located tumor or severe disease, surgical resection is currently the effective management; however, it also carries increased risks of function loss. The interdisciplinary field of regenerative medicine offers strategies that can potentially restore severely diseased and injured tissues and organs. Adipose-derived stromal cells (ASCs) are an abundant and accessible source of adult stem cells and hold great promise as therapeutic agents for tissue regeneration. In this work, we transplanted cells isolated from human stromal tissues, including a 6%-7% ASC population, into heat-damaged femoral muscles of non-obese diabetic immunodeficient mice. The movement of the limbs was observed to determine the functional recovery 3 months after transplantation. Among the mice that did not receive cell transplantation, 20% were able to walk with the injured limb touching the ground, while all of the mice in the ASC-treatment group were able to walk. Furthermore, all ASC-treated mice were able to stand on both back paws, in contrast to the control group mice. The human stromal cell population containing ASCs was able to differentiate and engraft the injured muscle tissues successfully. Our results indicate that stromal material/ASC-based therapies are a promising strategy for the regeneration of tissues and function restoration after severe injury due to surgery.

Background: Regenerative cell strategies rely on stromal cell implants to attain an observable clinical outcome. However, the effective cell dose to ensure a therapeutic response remains unknown. To achieve a higher cell dose, the authors hypothesized that reducing the volume occupied by mature adipocytes in lipoaspirate will concentrate the stromal vascular fraction present in the original tissue., Methods: Human standardized lipoaspirate (n = 6) was centrifuged (1200 g for 3 minutes) and the water phase was discarded. Mechanical disaggregation was achieved by shearing tissue through 2.4- and 1.2-mm Luer-to-Luer transfers. After a second centrifugation (800 g for 10 minutes), stromal cell aggregates were separated from the supernatant oil phase. Lipoaspirate percentage composition was determined by its constituent weights. Cell content was measured by total DNA quantification, and partial cell viability was determined by image cytometry. Tissue sections were evaluated histologically (hematoxylin and eosin and Masson trichrome stains)., Results: Stromal cell aggregates reduced the standardized lipoaspirate mass to 28.6 ± 4.2 percent. Accordingly, the cell density increased by 222.6 ± 63.3 percent (from 9.9 ± 1.4 million cells/g to 31.3 ± 6.6 million cells/g; p < 0.05). Cell viability was unaffected in stromal cell aggregates (71.3 ± 2.5 percent) compared to standardized lipoaspirate (72.2 ± 2.3 percent), and histologic analysis revealed high-density areas enriched with stromal cells (622.9 ± 145.6 percent) and extracellular matrix (871.2 ± 80.3 percent)., Conclusion: Stromal cell aggregates represent a biological agent that triplicates the cell density versus unprocessed lipoaspirate, low on oil and water fluids, and enriched extracellular matrix components.

Background: The stromal vascular fraction can improve volume retention after fat grafting, but the optimal stromal vascular fraction extraction method remains controversial. This study investigated the effect of mechanical vibration on stromal vascular fraction activity and explored the efficacy of vibration as a new extraction method compared to centrifugation, enzyme digestion, and nanoemulsion methods., Methods: Twenty-four rabbits were divided into three groups, and adipose tissue was harvested from the scapular region of each rabbit. In the first group, stromal vascular fraction was extracted from adipose tissue by vibration with different frequencies and durations. Cell counts and colony formation were assessed to determine the optimal vibration parameters. In the second group, stromal vascular fraction was extracted by the four methods, and the cell counts, proliferation, and adipogenic capabilities were observed in vitro. In the third group, adipose tissue mixed with stromal vascular fraction extracted by means of the four methods was grafted into rabbit ears. Volume retention and histologic changes were evaluated over 24 weeks., Results: Stromal vascular fraction activity was not influenced by low-frequency (≤45 Hz) and short-duration (≤20 minutes) vibrations. Vibration at 30 Hz for 15 minutes was most efficient for stromal vascular fraction extraction. In vitro, stromal vascular fraction extracted by vibration showed advantages for cell viability. In vivo, the vibration group showed a more normal tissue morphology and a higher retention rate (60.68 ± 7.07 percent) than the enzyme digestion (31.88 ± 4.99 percent), centrifugation (43.76 ± 4.32 percent), and nanoemulsion groups (21.79 ± 3.57 percent) (p < 0.05)., Conclusion: Vibration at 30 Hz for 15 minutes is recommended as a novel nonenzymatic method to extract stromal vascular fraction with high activity.

Objectives: The aim of this study was to evaluate the safety and efficacy of the use of FG-SVFs in face rejuvenation for esthetic improvement., Methods: 33 female patients affected by face's soft-tissue defects with loss of volume, study group (SG), were treated with FG-SVFs, comparing results with a control group (CG) (n = 30) treated with fat graft not enhanced (FG). Clinical evaluation, a photographic assessment, magnetic resonance imaging (MRI), and ultrasound (US) were performed. Post-operative follow-up was performed at 1, 3, 7, 12, 24, 48, weeks, and then annually., Results: SG patients showed 61% maintenance of the contour restoring and of volume after 3 years compared with the CG treated with FG, who showed 31% maintenance. 60.7% (n = 20) of SG patients, presented an increase of 6.6 mm in the soft tissue volume after 36 months, which was reported in only 33,3% (n = 10) of the CG. Volumetric persistence in the SG was higher than that in the CG (p <. 0001 vs. CG). MRI and US moreover confirmed the absence of important side effects, as fat necrosis, and cytosteatonecrotic areas., Conclusions: The use of FG-SVFs was safe and effective in this series of a case treated.

Introduction: Adipose-derived stromal cells (ADSCs) can be an important alternative in COVID-19 prevention, treatment, and subsequent sequelae repair. However, ACE-2 plays a common role in the pathogenesis of adipocyte hypertrophy and COVID 19., Areas Covered: In this 'Perspective,' the author would like to emphasize the use of adipose tissue-derived stromal cells in COVID 19 and the issues that clinicians should pay attention to in fat graft applications in terms of adipose tissue-RAS relationship. The new normal for adipose tissue in COVID 19 will be highlighted., Expert Opinion: ADSCs may potentially be used in COVID-19. However, it has been speculated that ACE2 receptors are responsible for the pathogenesis of adipose tissue overgrowth and may be a potential danger in terms of the relationship between ACE2 receptors and COVID19. We speculate that reducing the size of overgrown fat tissue by ultra-sharp blades and using near-normal adipocytes will create a 'new normal.'

Mesenchymal stromal cells (MSCs) are rare precursors in all organs of the body. MSCs have profound anti-inflammatory effects and reduce alloreactivity in vitro and in vivo . In pediatric allogeneic hematopoietic cell transplantation (HCT), MSCs have mainly been used to treat acute graft-versus-host disease (GVHD). MSCs are commercially available for this indication in Canada, Japan, and New Zeeland. More rare indications for MSCs in pediatric patients include graft failure and chronic GVHD. MSCs from bone marrow, adipose tissue, umbilical cord, Wharton's jelly, placenta tissue, and decidua have been used, but the optimal clinical stromal cell source has not been compared in clinical trials. More experimental clinical indications using MSCs, such as sepsis, acute respiratory distress syndrome, hemorrhages, pneumo-mediastinum, and neuroinflammation have primarily been explored in animal models or adult HCT patients. MSCs have almost no if any side-effects. In this pilot study we report the outcome of six children treated with decidua stromal cells (DSCs) for steroid refractory acute GVHD. At 6 months, complete response was seen in four patients and partial response in two patients. One child with high-risk ALL died from relapse and a boy with sickle cell disease died from a cerebral hemorrhage. Five-year survival was 67% and all survivors showed a Lansky score of 100%. To conclude, MSCs from various organs are well-tolerated and have shown an encouraging outcome for acute GVHD in pediatric patients., (Copyright © 2020 Ringdén, Gustafsson and Sadeghi.)

Background: Lymphedema is one of the most common complications following breast cancer. Axillary lymph node dissection and radiotherapy are two well-known risk factors resulting in either removal or damage to the lymph nodes. As stem cells are known for their regenerative capabilities, they could theoretically repair/restore the damaged lymph vessels leading to a decrease in lymphedema. Methods: We evaluated the treatment of SVF and ASC on a mouse lymphedema model. Forty-five mice were allocated into three groups containing 15 mice each. The SVF group was injected with 100 μl containing 1 × 10 6 SVF, the ASC group with 100 μl ml containing 1 × 10 6  ASC and the NS with 100 μl ml of NS. Volumes of the mice were assessed weekly by μCT hindlimb volumetry for a total of 8 weeks. Lymph vessel morphometry was assessed by cross-sections of both hindlimbs stained for anti-LYVE1. Lymphatic function was assessed by lymphatic clearance. Results: The volume change between the groups was non-significant throughout all 8 weeks. The immunohistochemistry showed a statistically significant difference between the hindlimbs in ASC vs. NS group p  = 0.032, 95% CI [-2121, -103]. Conclusion: The volume of the hindlimbs showed that treatment with SVF or ASC yielded very similar results compared to the control group when assessed after 8 weeks. In week two the biggest difference between ASC and NS was seen but the difference diminished during the 8 weeks. The secondary outcomes showed that the lymph vessel lumen decreased when treated with ASC compared to the control group. Lymphoscintigraphy yielded non-significant results.

Introduction: Stroke often causes residual hemiparesis, and upper extremity motor impairment is usually more disabling than lower extremity in those who are suffering from post-stroke hemiparesis. Cell therapy is one of the promising therapies to reduce post-stroke disability., Patient Concerns: Three male participants were included in the study to investigate the feasibility and tolerability of autologous adipose tissue derived stromal vascular fraction., Diagnosis: All participants had hemiparesis after 1st-ever stroke longer than 6 months previously., Interventions: Under general anesthesia, liposuction of abdominal subcutaneous fat was performed. Stromal vascular fraction freshly isolated from the adipose tissue extract was injected into the muscles of paretic upper extremity. All participants received inpatient stroke rehabilitation consisted of physical and occupational therapy more than 3 hours a day for 2 months or more., Outcomes: The whole procedure did not produce any significant adverse event in all participants. Adipose tissue extracts yielded sufficient stromal cells. One participant showed clinically important change in upper extremity Fugl-Meyer assessment after the injection and it lasted up to 6 months. Functional magnetic resonance imaging showed concomitant increase in ipsilesional cortical activity. The other 2 participants did not show remarkable changes., Lessons: Intramuscular injection of autologous adipose tissue derived stromal vascular fraction seems to be a safe and tolerable procedure in subjects with chronic stroke, and its utility in rehabilitation needs further investigation.

Background: Cell-assisted lipotransfer (CAL) promotes the survival of fat grafts with high vascular density and improves skin quality by increasing collagen content. However, no study has quantified the changes on the skin surface, and rigorous methodological evaluations are still lacking., Design: Fifty patients were recruited and randomly divided into two groups: an experimental group (n = 25) that underwent a stromal vascular fraction (SVF)-assisted fat graft and a control group (n = 25) that underwent fat graft only., Methods: The SVF cells were counted, tested in terms of viability, and characterized. The volumes of whole faces were determined by using a 3D scanner and Geomagic software preoperation, immediately after surgery, and 6 months postoperation. Facial skin qualities, including spots, wrinkles, texture, pores, UV spots, brown spots, red areas, and porphyrins, were detected by a VISIA skin detector preoperation and 6 months postoperation. A visual analog scale was used for clinical evaluation., Results: The cell pellet contained 1-3 × 10 7 /mL of fresh SVF cells. The cell viability exceeded 98%. The immunophenotyping characteristics and stemness were consistent with the features of adipose- derived stem cells (ADSCs). The survival rate of SVF-enriched fat grafts was significantly higher than that of control grafts: 77.6%±11.6% versus 56.2%±9.5% (p<0.001). The VISIA values of wrinkles (19.3 ± 6.6 versus 10.9 ± 5.5, p<0.001) and texture (15.8 ± 7.0 versus 10.3 ± 5.0, p<0.01) were significantly higher in SVF-enriched group than in control group at 6 months postoperation. During long-term follow-up, the majority of patients in both groups were satisfied with the final facial esthetic results., Conclusions: Our results demonstrated the positive outcomes of autologous SVF-assisted fat graft in improving facial skin quality and its promising application potential in clinical settings. This study is registered at www. ClinicalTrials.gov, number NCT02923219., Competing Interests: Declaration of Competing Interest None., (Copyright © 2019 British Association of Plastic, Reconstructive and Aesthetic Surgeons. Published by Elsevier Ltd. All rights reserved.)

Skeletal muscle regeneration depends on the satellite cells, which, in response to injury, activate, proliferate, and reconstruct damaged tissue. However, under certain conditions, such as large injuries or myopathies, these cells might not sufficiently support repair. Thus, other cell populations, among them adipose tissue-derived stromal cells (ADSCs), are tested as a tool to improve regeneration. Importantly, the pro-regenerative action of such cells could be improved by various factors. In the current study, we tested whether IL-4 and SDF-1 could improve the ability of ADSCs to support the regeneration of rat skeletal muscles. We compared their effect at properly regenerating fast-twitch EDL and poorly regenerating slow-twitch soleus. To this end, ADSCs subjected to IL-4 and SDF-1 were analyzed in vitro and also in vivo after their transplantation into injured muscles. We tested their proliferation rate, migration, expression of stem cell markers and myogenic factors, their ability to fuse with myoblasts, as well as their impact on the mass, structure and function of regenerating muscles. As a result, we showed that cytokine-pretreated ADSCs had a beneficial effect in the regeneration process. Their presence resulted in improved muscle structure and function, as well as decreased fibrosis development and a modulated immune response.

Background: Since antiquity, humans have been trying to devise remedies to cure androgenetic alopecia (AGA). These efforts include use of oral and topical concoctions and hair transplant strategies. As AGA affects people of all colors and creed, there has been a continuous effort to find a magic bullet against AGA. Unfortunately, to date, all the strategies to negate AGA effects have limitations and thus require new treatment options., Aim: To evaluate the efficacy of use of stromal vascular fraction (SVF) in androgenetic alopecia patients., Methods: Stromal vascular fraction was obtained by enzymatic digestion of autologous adipose tissue. The patients were divided into two groups, that is, platelet-rich plasma (PRP) group and SVF-PRP group. In PRP group, only PRP was injected, while in SVF-PRP group a mixture of PRP and SVF was injected in affected scalp areas. After two sessions (4 weeks apart), the patients in both groups were assessed and analyzed using various parameters., Results: Mean hair density in PRP group was increased from 52.44 hair/cm 2 to 63.72 hair/cm 2 (21.51% increase); while in SVF-PRP group, it was 37.66 hair/cm 2 before treatment and 57.11 hair/cm 2 after SVF-PRP therapy (51.64% increase). Percentage reduction in pull test was more significant in SVF-PRP group (80.78 ± 5.84) as compared to PRP group (34.01 ± 22.44). The physician and patient assessment scores also indicated a significant improvement in SVF-PRP group., Conclusion: A combined SVF-PRP therapy reversed effects of AGA more efficiently as compared to PRP therapy alone., (© 2019 Wiley Periodicals, Inc.)

Background: The infiltration of the stromal vascular fraction (SVF) of autologous adipose tissue to treat osteoarthritis has been used for several years demonstrating its safety and noticeable efficacy. This article presents clinical data from patients afftected by moderate and severe knee osteoarthritis demonstrating safety and clinical efficacy of the treatment when this autologous cell product is injected in the knee joint and patients evaluated post-operatively after 1 year. However, what do we know about the mechanism that underlies this clinical improvement? This article proposes, for the first time in our opinion, a hypothesis of the mode of action that involves structural and molecular interactions between SVF and infrapatellar fat pad (IFP). As consequence, there would be a re-education of intra-articular adipose tissue, which we consider a key player for the clinical effect observed in the mid and long term mainly due to immuno-regulatory mechanisms., Methods: This is a retrospective and not controlled study that evaluated 50 patients (100 joints) ranging from 50 to 89 years old, separated by age cohorts. Clinical efficacy was assessed using the Lequesne, WOMAC, and VAS scales, by ultrasound control and quantification of the biochemical profiles of synovial fluid., Results: There were no serious adverse effects. All the indexes studied showed a significant clinical improvement after 1-year follow-up for all ages and OA degree groups. This finding was correlated with the ultrasound observations and biochemical data, which show a marked decrease in catabolic and pro-inflammatory molecules (MMP-2, IL-1B, IL-6, and IL-8) and significant increase for anabolic and anti-inflammatory molecules (IGF-1 and IL-10)., Conclusions: We conclude that intra-articular SVF infiltration for knee OA treatment is safe and effective during 1 year. We propose that applied SVF cells cause a cascade of molecular and structural events that, through complex interactions between IFP and SVF, re-educating the intra-articular fatty tissue towards a homeostatic, protective, and anti-inflammatory function, which will ultimately promote the restructuring and regeneration of damaged tissues.

The complexity of mammary tissue and the variety of cells involved make tissue regeneration an ambitious goal. This review, supported by both detailed macro and micro anatomy, illustrates the potential of regenerative medicine in terms of mammary gland reconstruction to restore breast physiology and morphology, damaged by mastectomy. Despite the widespread use of conventional therapies, many critical issues have been solved using the potential of stem cells resident in adipose tissue, leading to commercial products. in vitro research has reported that adipose stem cells are the principal cellular source for reconstructing adipose tissue, ductal epithelium, and nipple structures. In addition to simple cell injection, construct made by cells seeded on a suitable biodegradable scaffold is a viable alternative from a long-term perspective. Preclinical studies on mice and clinical studies, most of which have reached Phase II, are essential in the commercialization of cellular therapy products. Recent studies have revealed that the enrichment of fat grafting with stromal vascular fraction cells is a viable alternative to breast reconstruction. Although in the future, organ-on-a-chip can be envisioned, for the moment researchers are still focusing on therapies that are a long way from regenerating the whole organ, but which nevertheless prevent complications, such as relapse and loss in terms of morphology., (© 2019 The Authors. Journal of Tissue Engineering and Regenerative Medicine published by John Wiley & Sons Ltd.)

Autologous fat graft has limitations, especially long-term unpredictability of volume maintenance. The mechanical enrichment of fat graft with adipose-derived stem cells (ADSCs) could guarantee the survival of fat grafts. After decantation, washing, and centrifugation of lipoaspirate, the authors carried out histochemical analysis and flow cytometry to determine the best layers for preparing ADSC-enriched fat. After centrifugation, the stromal vascular fraction (SVF) was separated by mechanical dissociation and mixed with another layer of intact adipocytes, which was injected into patients. All patients showed volumetric improvement after a single lipotransfer section, without overcorrection. The method is safe, has low cost, and is easily reproducible., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Hydrogels derived from corneal extracellular matrix (ECM) represent a promising biomaterial for corneal repair and regeneration. To fabricate these hydrogels, first corneas need to be decellularized using repeated freeze-thaw cycles and nucleases to remove all nuclear and cellular components. The remaining corneal ECM is lyophilized to remove all water and milled into a fine powder. The ECM powder is weighed and dissolved in pepsin solution at a concentration of 20 mg/mL. Hydrogels are formed by neutralizing the pH of the solution and maintaining it at 37 °C until fibrillogenesis has occurred. Corneal stromal cells may be suspended throughout the hydrogel solution prior to gelation to generate a corneal stromal substitute.

Background: No specific therapy exists for acute pancreatitis (AP), and current treatment remains entirely supportive. Adipose stem cells (ASCs) have significant immunomodulatory and regenerative activities. We hypothesized that systemic administration of ASCs would mitigate inflammation in AP., Methods: AP was induced in mice by 6 hourly intraperitoneal injections of cerulein. Twenty-four hours after AP induction, mice were randomized into four systemic treatment groups: sham group (no acute pancreatitis), vehicle, human ASCs, and human ASC-conditioned media. Mice were sacrificed at 48 h, and blood and organs were collected and analyzed. Pancreatic injury was quantified histologically using a published score (edema, inflammation, and necrosis). Pancreatic inflammation was also studied by immunohistochemistry and PCR., Results: When using IV infusion of Hoechst-labeled ASCs, ASCs were found to localize to inflamed tissues: lungs and pancreas. Mice treated with ASCs had less severe AP, as shown by a significantly decreased histopathology score (edema, inflammation, and necrosis) (p = 0.001). ASCs infusion polarized pancreatic macrophages toward an anti-inflammatory M2 phenotype. ASC-conditioned media reduced pancreatic inflammation similarly to ASCs only, highlighting the importance of ASCs secreted factors in modulating inflammation., Conclusion: Intravenous delivery of human ASCs markedly reduces pancreatic inflammation in a murine model of AP ASCs which represent an effective therapy for AP.

Kidney regenerative medicine is expected to be the solution to the shortage of organs for transplantation. In a previous report, we transplanted exogenous renal progenitor cells (RPCs) including nephron progenitor cells (NPCs), stromal progenitor cells (SPCs), and the ureteric bud (UB) into the nephrogenic zone of animal embryos and succeeded in regenerating new nephrons from exogenous NPCs through a fetal developmental program. However, it was unknown whether the renal stromal lineage cells were regenerated from SPCs. The present study aimed to verify the differentiation of SPCs into mesangial cells and renal stromal lineage cells. Here, we found that simply transplanting RPCs, including SPCs, into the nephrogenic zone of wild-type fetal mice was insufficient for differentiation of SPCs. Therefore, to enrich the purity of SPCs, we sorted cells from RPCs by targeting platelet-derived growth factor receptor alpha (PDGFRa) which is a cell surface marker for immature stromal cells and transplanted the PDGFRa-positive sorted cells. As a result, we succeeded in regenerating a large number of mesangial cells and other renal stromal lineage cells including interstitial fibroblasts, vascular pericytes, and juxtaglomerular cells. We have established the method for regeneration of stromal cells from exogenous SPCs that may contribute to various fields, such as regenerative medicine and kidney embryology, and the creation of disease models for renal stromal disorders., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Purpose: To establish Myh11 as a marker of a subset of corneal endothelial cells (CECs), and to demonstrate the feasibility of restoring the corneal endothelium with Myh11-lineage (Myh11-Lin[+]) adipose-derived stromal cells (ASCs)., Methods: Intraperitoneal administration of tamoxifen and (Z)-4-hydroxytamoxifen eyedrops were used to trace the lineage of Myh11-expressing cells with the Myh11-Cre-ERT2-flox-tdTomato mouse model. Immunostaining and Western blot characterized marker expression and spatial distribution of Myh11-Lin(+) cells in the cornea, and administration of 5-ethynyl-2'-deoxyuridine labeled proliferating cells. ASCs were isolated from epididymal adipose Myh11+ mural cells and treated with cornea differentiation media to evaluate corneal endothelial differentiation potential. Differentiated ASCs were injected into the anterior chamber to test for incorporation into corneal endothelium following scratch injury., Results: A subset of CECs express Myh11, a marker previously thought restricted to only mural cells. Myh11-Lin(+) CECs marked a stable subpopulation of cells in the cornea endothelium. Myh11-Lin(+) ASCs undergo CEC differentiation in vitro and incorporate into injured corneal endothelium., Conclusions: Dystrophy and dysfunction of the corneal endothelium accounts for almost half of all corneal transplants, the maintenance of the cornea endothelium is poorly understood, and there are a lack of mouse models to study specific CEC populations. We establish a mouse model that can trace the cell fate of a subpopulation of CECs based on Myh11 expression. A subset of ASCs that share this Myh11 transcriptional lineage are capable of differentiating into CECs that can incorporate into injured corneal endothelium, revealing a potential cell source for creating engineered transplant material.

The stromal vascular fraction (SVF) obtained from inguinal adipose tissue was injected into the sciatic nerve region in diabetic rats. The effects of the SVF on the sciatic nerve and functional, electrophysiological and histopathological changes were examined in this study. Rats were divided into five groups; a non-diabetic control group, and four diabetic groups. In the first diabetic rat group, the SVF was obtained from inguinal adipose tissue. The remaining diabetic groups included a sham control group, a phosphate-buffered saline (PBS) injection group and an SVF injection group. Injections were made into the sciatic nerve region. Electromyography and walking track analyses were conducted on all groups at the beginning of the experiment. Diabetes was induced via a single dose of streptozotocin. Walking track analysis and electromyography measurements were repeated in week 8. SVF or PBS was injected into the right sciatic nerve region on week 8 of experiment group rats. Walking track analysis and electromyography were repeated in week 12 and all sciatic nerves were examined histopathologically. In the diabetic SVF group, the sciatic functional index calculated from walking track analysis in week 12 was better than week 8. Additionally, the myelin sheaths of the right sciatic nerve were thicker and more uniform and the nerve fibers were thicker than those of the left, untreated sciatic nerve. No statistical differences were detected in electromyographic measurements. The adipose-derived SVF may be beneficial for nerve regeneration in diabetic neuropathy.

Placenta-derived decidua stromal cells (DSCs) are being investigated as an alternative to other sources of mesenchymal stromal cells (MSCs) for cellular therapy. DSCs are more effective in treating acute inflammatory diseases in human and this is our preclinical safety study of human DSCs in Sprague-Dawley rats and Balb/c mice. Human DSCs were cultured and expanded from fetal membranes obtained from placentas following cesarean section. In rats, 0.5 × 10 6 cells/kg were injected intravenously ( n = 4) or intra-aortal ( n = 4). In mice, DSCs were given intravenously at doses ranging from 4-40 × 10 6 cells/kg (total of n = 120 mice). In vivo tracking of human cells in mice was performed by using transduced DSC with luciferin gene, and in rats by using 18 F-FDG PET. Clotting parameters were determined in vitro and in vivo . All intra-arterially DSC-treated rats had normal motility and behavior and histological examination was normal for liver, spleen kidneys and thigh muscles. Mice treated with DSCs showed no immediate or long-term side effects. None of the mice died or showed acute toxicity or adverse reactions 3 and 30 days after DSC infusion. Murine blood biochemistry profiles related to liver, kidney, heart, and inflammatory indices was not influenced by DSC infusion and complete blood counts were normal. In vivo tracking of infused DSCs detected a signal in the lungs for up to 4 days post infusion. Compared to bone marrow derived MSCs, the DSCs had better viability, smaller size, but stronger clotting in human blood and plasma. Both MSC- and DSC-induced coagulation and complement activation markers, thrombin-anti-thrombin complex (TAT) and C3a, and in vitro clotting parameters were decreased by heparin supplementation. In conclusion, DSCs are safe with almost no side effects even with doses 40 times higher than are used clinically, particularly when supplemented with low-dose heparin., (Copyright © 2019 Sadeghi, Moretti, Arnberg, Samén, Kohein, Catar, Kamhieh-Milz, Geissler, Moll, Holmin and Ringdén.)