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Objective: Body mass index is known to contribute to outcomes for patients with knee osteoarthritis. Furthermore, body mass index influences the protein expression of orthobiologic treatments like plateletrich plasma and microfragmented adipose tissue. We performed a secondary analysis of the association of body mass index with patientreported outcomes for patients with knee osteoarthritis who received either platelet-rich plasma or microfragmented adipose tissue injections. Methods: Seventy-one patients with knee osteoarthritis were randomized to receive a single ultrasound-guided injection of platelet-rich plasma or microfragmented adipose tissue. Platelet-rich plasma was created from 180 cc of anticoagulated blood and processed using a double-spin, buffy-coat concentration system. Microfragmented adipose tissue was created using autologous lipoaspirate that was processed according to minimal manipulation guidelines. Patient-reported outcomes and osteoarthritis outcome scores (Knee Osteoarthritis and injury Outcome Score) were tracked for 12 mos. Results: Forty-nine patients (platelet-rich plasma = 23, microfragmented adipose tissue = 26) completed 12-mo follow-up. Knee Osteoarthritis and injury Outcome Score quality of life and activity of daily living subscores were inversely correlated (both P < 0.05) with body mass index in the microfragmented adipose tissue but not platelet-rich plasmagroup. Knee Osteoarthritis and injury Outcome Score pain and sport subscores showed a trend toward inverse correlation with body mass index in the microfragmented adipose tissue group (P = 0.07 and P = 0.06, respectively), but not platelet-rich plasma. Conclusions: Body mass index was negatively associated with patient-reported outcomes in patients who received microfragmented adipose tissue injections for knee osteoarthritis, but not for patients receiving platelet-rich plasma. [ABSTRACT FROM AUTHOR]

Background: Platelet-rich plasma (PRP) is an effective treatment for knee osteoarthritis (OA). Microfragmented adipose tissue (MFAT) is another orthobiologic that holds promise, but data supporting its use are limited. Previous studies showed that MFAT created using the Lipogems device was equivalent to PRP created via noncommercial laboratory-based processes. Purpose: To perform a comparison of commercially available MFAT and PRP systems for treatment of knee OA. Study Design: Randomized controlled trial; Level of evidence, 2. Methods: A total of 71 patients with symptomatic knee OA (Kellgren-Lawrence grades 1-4) were randomized to receive a single injection of either leukocyte-rich PRP (Angel; Arthrex) or MFAT (Lipogems) under ultrasound guidance. Patient-reported outcomes (Knee injury and Osteoarthritis Outcome Score [KOOS], visual analog scale for pain with activities of daily living [VAS pain], and Tegner activity level) were recorded at baseline and at 1, 3, 6, and 12 months after injection. The primary outcome was the KOOS-Pain subscale score at 12 months after injection. Results: Overall, 49 patients completed their 12-month follow-up (PRP group, n = 23; MFAT group, n = 26). All demographic features were similar between groups, except that more men were randomized to the PRP group and more women to the MFAT group. At 12 months posttreatment, KOOS-Pain scores improved in both groups, with no significant group difference (PRP, 78 ± 17.9 vs MFAT, 77.8 ± 19.3; P =.69). Similarly, other KOOS subscales, VAS pain scores, and Tegner scores improved at 12 months, with no differences between treatment groups. Conclusion: Both PRP and MFAT injections for knee OA resulted in improved patient-reported outcomes at 12 months posttreatment, with no differences found between treatments. Registration: NCT04351087 (ClinicalTrials.gov identifier). [ABSTRACT FROM AUTHOR]

A 70-year-old female presented with an 8-month history of right anterior shoulder pain and weakness, unresolved with conservative management. Among other shoulder pathology, the patient was diagnosed with a full-thickness supraspinatus tear and elected to proceed with the microfragmented adipose tissue procedure to treat the injured tendon and nearby relevant structures. Improvements in pain and function were documented along with progressive healing of the supraspinatus on ultrasound and MRI following the procedure. This case demonstrates the efficacy of microfragmented adipose tissue as a relatively novel approach to treating non-retracted, full-thickness rotator cuff tears. Fat is an excellent source of stem cells and collagen protein fibers known as a matrix. Mesenchymal stem cells can differentiate into a variety of other cell types. Collagen provides structure and is a major component of muscles and tendons. When transferring stem cells from one's own fat, these cells can support the body's repair process of injured tissue, such as rotator cuff tears of the shoulder. In this case, a patient with a long history of shoulder pain and weakness was diagnosed with a full-thickness tear of one of the four muscles that make up the rotator cuff. Full-thickness tears, compared with partial-thickness tears, are larger, deeper tears that extend across the tendon. This is an injury that has historically been limited to either conservative management (living with the pain) or surgery. The patient underwent a nonsurgical alternative, known as the microfragmented adipose tissue procedure, to repair the injured tendon. Fat was transferred from her hips and injected into the rotator cuff tear of the shoulder. She experienced improvements in pain and function as the tendon healed, documented using ultrasound and MRI. This case supports the benefit of microfragmented adipose tissue, a newer, less invasive approach to treating musculoskeletal injuries, even those as severe as a full-thickness rotator cuff tear. Microfragmented adipose tissue in the treatment of a non-retracted, full-thickness supraspinatus tear. [ABSTRACT FROM AUTHOR]

The biological enhancement of tissue regeneration and healing is an appealing perspective in orthopedics. We aimed to conduct a systematic review to describe the global distribution of studies investigating the use of adipose tissue derivates in orthopedics and to provide information on their quality and on the products available. The quality of the included studies was assessed using the modified Coleman Methodology Score (mCMS) and the Cochrane risk-of-bias tool for randomized trials. Eighty-two studies were included, with a total of 3594 patients treated. In total, 70% of the studies investigated the treatment of knee disorders, predominantly osteoarthritis; 26% of all studies dealt with expanded adipose-derived stem/stromal cells (ADSCs), 72% of which had stromal vascular fraction (SVF); 70% described the injection of adipose tissue derivates into the affected site; and 24% described arthroscopies with the addition of adipose tissue derivates. The mean mCMS for all studies was 51.7 ± 21.4 points, with a significantly higher score for the studies dealing with expanded ADSCs compared to those dealing with SVF (p = 0.0027). Our analysis shows high heterogeneity in terms of the types of performed procedures as well as the choice and processing of adipose tissue derivates. [ABSTRACT FROM AUTHOR]

Purpose: The purpose of this prospective randomized clinical trial is to compare the clinical outcomes of three injections of leucocyte-poor platelet-rich plasma (LP-PRP) and hyaluronic acid (HA) to a single dose of autologous microfragmented adipose tissue (AMAT) in patients with mild osteoarthritis at a two-year follow-up. Methods: Eighty symptomatic knees in fifty patients (mean age: 62.38 ± 11.88 years) with Kellgren-Lawrence grade 0 to 2 osteoarthritis were non blinded, randomly allocated into two equal groups. Group 1 consisted of 40 knees that received autologous LP-PRP + HA; Group 2 consisted of 40 knees treated with a single dose of AMAT injection. The outcomes were measured by Tegner, Marx, Visual Analogue Scale (VAS) for pain, International Knee Documentation Committee, and Knee Injury and Osteoarthritis Outcome Score (KOOS) at 6 (T1), 12 (T2), and 24 (T3) months. Adverse events were recorded at each follow-up timepoint. To assess score differences among subjects of the same gender and age, a subgroup analysis was performed. Results: Both groups had significant clinical and functional improvement at 6, 12, and 24 months (p < 0.05). Comparing the two groups, the AMAT groups showed significantly higher pre-operative Marx score (3.35 ± 4.91 vs. 1.78 ± 3.91) and VAS score (5.03 ± 2.02 vs. 3.85 ± 1.68) (p < 0.05), higher VAS (3.89 ± 2.51 vs. 2.64 ± 2.00) at T2 and KOOS-ADL (79.60 ± 20.20 vs. 65.68 ± 23.62), and lower KOOS-Sports (50.30 ± 30.15 vs. 68.35 ± 30.39) at T3 (p < 0.05). No patient from either group had experienced major adverse effects. In the LP-PRP group 12 (30%) patients presented swelling, redness, and mild pain for one day after injection and two patients had synovitis for two days and required paracetamol and local ice. In AMAT group 5 (12.5%) patients had ecchymosis and bruising at the fat aspiration site for three days. Conclusion: AMAT did not show significant superior clinical improvement compared with three LP-PRP combined with HA injections in terms of functional improvement at different follow-up points. Both procedures were safe with no major complications reporting good results at mid-term follow-up, improving knee function, pain, and quality of live regardless of age and gender. Level of evidence: Level I—Prospective Randomized Clinical Trial. [ABSTRACT FROM AUTHOR]

Simple Summary: Bone healing is a proliferative physiological process mediated by a complex interaction between biological and biomechanical mechanisms. Major complications of fracture repair and osteotomies include delayed union, non-union, and malunion. Adipose stem cells (ADSCs) have been shown to have positive effects on bone healing. In response to microenvironment signals, ADSCs can differentiate into osteogenic-like cells; moreover, they produce several cytokines and growth factors that are directly involved in bone healing. In clinical practice, ADSCs are often not administered as a pure isolate but rather as a constituent of microfragmented adipose tissue (MFAT) due to processing time and legislative restrictions. The purpose of this prospective, randomised, blinded, in vivo clinical study was to estimate the effect of autologous MFAT on bone healing in dogs who underwent tibial plateau levelling osteotomy. The results suggest that administration of MFAT is safe, cost-effective, minimally invasive, saves time, and could accelerate the bone healing of osteotomies or acute fractures. Additionally, the canine model adopted in this study could play a key role in developing successful treatments for translational medicine. The aim of this study was to evaluate the effects of autologous microfragmented adipose tissue (MFAT) applied after mechanical fragmentation and assess these effects radiographically in bone healing in dogs subjected to tibial plateau levelling osteotomy (TPLO). Twenty dogs with unilateral cranial cruciate ligament disease were enrolled and randomly assigned to the treatment group (MFAT) or the control group (NT). The MFAT group underwent TPLO and autologous MFAT intra-articular administration, while the NT group underwent TPLO alone. Adipose tissue was collected from the thigh region, and MFAT was obtained by mechanical fragmentation at the end of the surgery. The patients were subjected to X-ray examination preoperatively, immediately postoperatively (T0), and at 4 (T1) and 8 (T2) weeks postoperatively. Two radiographic scores that had previously been described for the evaluation of bone healing after TPLO were used. A 12-point scoring system (from 0 = no healing to 12 = complete remodelling) was used at T0, T1, and T2, while a 5-point scoring system (from 0 = no healing to 4 = 76–100% of healing) was used at T1 and T2. The median healing scores were significantly higher at T1 and T2 for the MFAT group compared with the NT group for the 12-point (p < 0.05) and 5-point (p < 0.05) scoring systems. The intra-articular injection of autologous microfragmented adipose tissue can accelerate bone healing after TPLO without complications. [ABSTRACT FROM AUTHOR]

Our patient presented with a 1-year history of right sided Achilles tendon pain and weakness due to partial intrasubstance tear. The injury was refractory to conservative treatment, leading to a trial injection of microfragmented adipose tissue. Progressive healing and improved function were documented on physical exam and sonographically at subsequent follow-up appointments. About 4 weeks following the injection, the patient was able to return to his regular activity level. At the 6 month follow-up appointment, the patient continued to be pain free and had resumed all prior activities without limitations. This case highlights the potential microfragmented adipose tissue has as a regenerative treatment modality for the management of partial Achilles tendon tears. Microfragmented adipose tissue in the treatment of a chronic Achilles tendon tear refractory to conservative treatment. [ABSTRACT FROM AUTHOR]

Background: Platelet-rich plasma (PRP) has been established as safe and effective for knee osteoarthritis (OA). Another orthobiologic therapy, microfragmented adipose tissue (MFAT), has gained attention because of its heterogeneous cell population (including mesenchymal stem cells). However, prospective comparative data on MFAT are lacking. Because of the safety, efficacy, and simplicity of PRP, new therapeutics such as MFAT should be compared directly with PRP. Purpose: To compare patient-reported outcomes of a single injection of PRP versus MFAT for knee OA. Study Design: Randomized controlled trial; Level of evidence, 2. Methods: A total of 58 patients with symptomatic knee OA (Kellgren-Lawrence grades 1-4) were randomized to receive a single injection of either leukocyte-rich PRP or MFAT under ultrasound guidance. PRP was created by processing 156 mL of whole blood. MFAT was created by harvesting 30 mL of adipose tissue via standard lipoaspiration. Scores for the Knee injury and Osteoarthritis Outcome Score (KOOS) subscales and visual analog scale for pain with Activities of Daily Living (VAS-ADL) were recorded at baseline and at 1, 3, and 6 months after the injection. The primary outcome was the KOOS–Pain subscore at 6 months after the injection. Results: The PRP group (n = 30) had a mean volume of 5.12 ± 1.12 mL injected. This consisted of a mean platelet count of 2673.72 ± 1139.04 × 103/µL and mean leukocyte count of 25.36 ± 13.27 × 103/µL (67.81% lymphocytes, 18.66% monocytes, and 12.33% neutrophils). The MFAT group (n = 28) had a mean volume of 7.92 ± 3.87 mL injected. The mean total nucleated cell count was 3.56 ± 4.62 million/mL. In both groups, KOOS subscale and VAS-ADL scores improved from baseline, and there was no significant difference between the PRP and MFAT groups in the final KOOS–Pain subscore (80.38 ± 16.07 vs 81.61 ± 16.37, respectively; P =.67) or any other outcome score. Conclusion: A single injection of either PRP or MFAT resulted in a clinically meaningful improvement for patients with knee OA at 6 months, with no difference between treatment groups. Registration: NCT04351087 (ClinicalTrials.gov identifier). [ABSTRACT FROM AUTHOR]

The aim of this study was to evaluate the effects of autologous microfragmented adipose tissue (MFAT) applied after mechanical fragmentation and assess these effects radiographically in bone healing in dogs subjected to tibial plateau levelling osteotomy (TPLO). Twenty dogs with unilateral cranial cruciate ligament disease were enrolled and randomly assigned to the treatment group (MFAT) or the control group (NT). The MFAT group underwent TPLO and autologous MFAT intra-articular administration, while the NT group underwent TPLO alone. Adipose tissue was collected from the thigh region, and MFAT was obtained by mechanical fragmentation at the end of the surgery. The patients were subjected to X-ray examination preoperatively, immediately postoperatively (T0), and at 4 (T1) and 8 (T2) weeks postoperatively. Two radiographic scores that had previously been described for the evaluation of bone healing after TPLO were used. A 12-point scoring system (from 0 = no healing to 12 = complete remodelling) was used at T0, T1, and T2, while a 5-point scoring system (from 0 = no healing to 4 = 76–100% of healing) was used at T1 and T2. The median healing scores were significantly higher at T1 and T2 for the MFAT group compared with the NT group for the 12-point (p < 0.05) and 5-point (p < 0.05) scoring systems. The intra-articular injection of autologous microfragmented adipose tissue can accelerate bone healing after TPLO without complications.

Simple Summary: Osteoarthritis (OA) is a very common musculoskeletal condition that affects dogs, as well as humans and other species, and causes pain, lameness, and disability. Since therapy is not always effective and is definitive only in some cases, OA is still a leading cause of euthanasia in dogs and a challenge for orthopedic surgeons. Recently, new therapeutic approaches, such as the use of autologous mesenchymal stem cells, have been developed. The purpose of this prospective, randomized, controlled, in vivo clinical study was to estimate the safety, feasibility, and efficacy of the intra-articular treatment of autologous microfragmented adipose tissue in dogs affected by spontaneous OA in comparison with a treatment with hyaluronic acid. Pain, lameness, the radiographic progression of OA, and synovial fluid inflammation were assessed. The results suggest that intra-articular injection of microfragmented autologous adipose tissue is safe, timesaving, cost-effective, minimally invasive, and can be easily done in one step. This treatment, compared with the hyaluronic acid treatment, showed better long-term pain control and an amelioration of synovial fluid quality, resulting in an improvement in joint function. This new treatment can be included among the effective therapies for OA. Additionally, the canine spontaneous OA model adopted in this study could play a key role in developing successful treatments for translational medicine. The purpose of this study was to estimate the safety, feasibility, and efficacy of the intra-articular treatment of autologous microfragmented adipose tissue in dogs with spontaneous osteoarthritis (OA) in comparison with hyaluronic acid (HA), the standard intra-articular treatment. Specifically, it clinically evaluated pain and lameness, the radiographic progression of osteoarthritis, and synovial fluid inflammation. This was a prospective, single-center, parallel-group, randomized, controlled, in vivo clinical study. Participants (n = 40) received either a single intra-articular injection of microfragmented adipose tissue or a single intra-articular injection of HA (1:1). Clinical outcomes were determined using a specialistic clinician assessment obtained by the completion of a specific clinical form based on the Vesseur modified lameness classification system, a pain evaluation using the Visual Analogue Scale (VAS), the measurement of the range of motion (ROM) of the affected joint, limb circumference, and the owners' score evaluation using the Canine Brief Pain Inventory (CBPI) for up to 6 months after the time of injection. Patients underwent a radiographic examination to establish the degree of OA in the affected joint, and synovial fluid samples were collected to assess the biochemical environment of the joint and evaluate and quantify the cellular population and the presence of three specific inflammation biomarkers for up to 60 days. The results of this study suggest that microfragmented autologous adipose tissue is safe and can effectively relieve pain and improve function in dogs with spontaneous articular OA. This one-step procedure is simple, timesaving, cost-effective, minimally invasive, and eliminates the need for complex and time-intensive cell culture processing. Furthermore, the clinical evidence and cytological results suggest better long-term pain control, resulting in an improvement in joint function, compared to HA treatment. The canine spontaneous OA model could play a key role in developing successful treatments for human medicine. [ABSTRACT FROM AUTHOR]

The purpose of this study was to estimate the safety, feasibility, and efficacy of the intra-articular treatment of autologous microfragmented adipose tissue in dogs with spontaneous osteoarthritis (OA) in comparison with hyaluronic acid (HA), the standard intra-articular treatment. Specifically, it clinically evaluated pain and lameness, the radiographic progression of osteoarthritis, and synovial fluid inflammation. This was a prospective, single-center, parallel-group, randomized, controlled, in vivo clinical study. Participants (n = 40) received either a single intra-articular injection of microfragmented adipose tissue or a single intra-articular injection of HA (1:1). Clinical outcomes were determined using a specialistic clinician assessment obtained by the completion of a specific clinical form based on the Vesseur modified lameness classification system, a pain evaluation using the Visual Analogue Scale (VAS), the measurement of the range of motion (ROM) of the affected joint, limb circumference, and the owners’ score evaluation using the Canine Brief Pain Inventory (CBPI) for up to 6 months after the time of injection. Patients underwent a radiographic examination to establish the degree of OA in the affected joint, and synovial fluid samples were collected to assess the biochemical environment of the joint and evaluate and quantify the cellular population and the presence of three specific inflammation biomarkers for up to 60 days. The results of this study suggest that microfragmented autologous adipose tissue is safe and can effectively relieve pain and improve function in dogs with spontaneous articular OA. This one-step procedure is simple, timesaving, cost-effective, minimally invasive, and eliminates the need for complex and time-intensive cell culture processing. Furthermore, the clinical evidence and cytological results suggest better long-term pain control, resulting in an improvement in joint function, compared to HA treatment. The canine spontaneous OA model could play a key role in developing successful treatments for human medicine.

Purpose: Rotator cuff tears are common musculoskeletal disorders, and surgical repair is characterized by a high rate of re-tear. Regenerative medicine strategies, in particular mesenchymal stem cell–based therapies, have been proposed to enhance tendon healing and reduce the re-tear rate. Autologous microfragmented adipose tissue (μFAT) allows for the clinical application of cell therapies and showed the ability to improve tenocyte proliferation and viability in previous in vitro assessments. The hypothesis of this study is that μFAT paracrine action would reduce the catabolic and inflammatory marker expression in tendon cells (TCs) derived from injured supraspinatus tendon (SST). Methods: TCs derived from injured SST were co-cultured with autologous μFAT in transwell for 48 h. Metabolic activity, DNA content, the content of soluble mediators in the media, and the gene expression of tendon-specific, inflammatory, and catabolic markers were analyzed. Results: μFAT-treated TCs showed a reduced expression of PTGS2 and MMP-3 with respect to untreated controls. Increased IL-1Ra, VEGF, and IL-6 content were observed in the media of μFAT-treated samples, in comparison with untreated TCs. Conclusion: μFAT exerted an anti-inflammatory action on supraspinatus tendon cells in vitro through paracrine action, resulting in the reduction of catabolic and inflammatory marker expression. These observations potentially support the use of μFAT as adjuvant therapy in the treatment of rotator cuff disease. [ABSTRACT FROM AUTHOR]

Within the adult canine population, disabilities and symptoms including joint pain and functional impairment are commonly observed in articular cartilage lesions and present a challenging feat in the operating room. Clinical settings require less invasive and more minimally manipulated measures facilitated by innovative and advanced technology. Mesenchymal stem cells have recently been proposed and, furthermore, autologous adipose tissue administration via injection has emerged as a new albeit somewhat controversial therapeutic tool. The purpose of this study is to characterize canine autologous micro-fragmented adipose tissue (micrografts) by mechanical approach without substantial manipulations. Adipose tissue samples collected from six dogs were processed by a Rigenera device and by enzymatic digestion from two different body regions (lumbar and thigh region). Interestingly, the immunophenotypic analysis attested that cells from Rigenera® were highly positive for the mesenchymal stem cells markers CD73 and CD90, less positive for hematopoietic CD45 and CD34, and negative for MHC class II antibodies (which play a role in immune responses). Finally, the Rigenera® technology obtained micrografts with a 35% higher expression of the IL10 gene with relevant anti-inflammatory activities compared to the enzymatic digestion protocol. This evidence suggests a potential improved clinical outcome capable of modulating inflammation and immune responses.

Background: Osteoarthritis (OA) is the most prevalent form of degenerative whole-joint disease. Before the final option of knee replacement, arthroscopic surgery was the most widely used joint-preserving surgical treatment. Emerging regenerative therapies, such as those involving platelet-rich plasma, mesenchymal stem cells, and microfragmented adipose tissue (MFAT), have been pushed to the forefront of treatment to prevent the progression of OA. Currently, MFAT has been successfully applied to treat different types of orthopedic diseases., Aim: To assess the efficacy and safety of MFAT with arthroscopic surgery in patients with knee OA (KOA)., Methods: A randomized, multicenter study was conducted between June 2017 and November 2022 in 10 hospitals in Zhejiang, China. Overall, 302 patients diagnosed with KOA (Kellgren-Lawrence grades 2-3) were randomized to the MFAT group ( n = 151, were administered MFAT following arthroscopic surgery), or the control group ( n = 151, were administered hyaluronic acid following arthroscopic surgery). The study outcomes were changes in the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) score, the visual analog scale (VAS) score, the Lequesne index score, the Whole-Organ Magnetic Resonance Imaging Score (WORMS), and safety over a 24-mo period from baseline., Results: The changes in the WOMAC score (including the three subscale scores), VAS pain score, and Lequesne index score at the 24-mo mark were significantly different in the MFAT and control groups, as well as when comparing values at the posttreatment visit and those at baseline ( P < 0.001). The MFAT group consistently demonstrated significant decreases in the WOMAC pain scores and VAS scores at all follow-ups compared to the control group ( P < 0.05). Furthermore, the WOMAC stiffness score, WOMAC function score, and Lequesne index score differed significantly between the groups at 12 and 24 mo ( P < 0.05). However, no significant between-group differences were observed in the WORMS at 24 mo ( P = 0.367). No serious adverse events occurred in both groups., Conclusion: The MFAT injection combined with arthroscopic surgery treatment group showed better mid-term clinical outcomes compared to the control group, suggesting its efficacy as a therapeutic approach for patients with KOA., Competing Interests: Conflict-of-interest statement: All the authors report no relevant conflicts of interest for this article., (©The Author(s) 2023. Published by Baishideng Publishing Group Inc. All rights reserved.)

Simple Summary: Mesenchymal stem cells are located in bone marrow, adipose tissue, synovial membrane, and muscular tissue. They have an immunosuppressive, anti-inflammatory, and antifibrotic effect. Tissue engineering considers the usage of mesenchymal stem cells as a possible option for regenerating tissues, with respect to bone and cartilage, due to their ability to differentiate into multiple cytotypes (including chondrocytes and osteoblasts). Herein, we characterize a non-invasive solution based on Rigenera® technology, a mechanical disaggregation method able to produce autologous adipose tissue-derived micrografts which are analogous to adipose-derived stem cells. Within the adult canine population, disabilities and symptoms including joint pain and functional impairment are commonly observed in articular cartilage lesions and present a challenging feat in the operating room. Clinical settings require less invasive and more minimally manipulated measures facilitated by innovative and advanced technology. Mesenchymal stem cells have recently been proposed and, furthermore, autologous adipose tissue administration via injection has emerged as a new albeit somewhat controversial therapeutic tool. The purpose of this study is to characterize canine autologous micro-fragmented adipose tissue (micrografts) by mechanical approach without substantial manipulations. Adipose tissue samples collected from six dogs were processed by a Rigenera device and by enzymatic digestion from two different body regions (lumbar and thigh region). Interestingly, the immunophenotypic analysis attested that cells from Rigenera® were highly positive for the mesenchymal stem cells markers CD73 and CD90, less positive for hematopoietic CD45 and CD34, and negative for MHC class II antibodies (which play a role in immune responses). Finally, the Rigenera® technology obtained micrografts with a 35% higher expression of the IL10 gene with relevant anti-inflammatory activities compared to the enzymatic digestion protocol. This evidence suggests a potential improved clinical outcome capable of modulating inflammation and immune responses. [ABSTRACT FROM AUTHOR]

Background: Complex perianal fistulas represent one of the most challenging manifestations of Crohn's disease. Combined surgical and medical therapy with biologic drugs today represent the first-line treatment option, but its efficacy does not exceed 60%. Recently, new therapeutic approaches, such as the use of mesenchymal stromal cells, have shown promising results. The adipose tissue is an abundant and easy to access source. The effectiveness, safety, and feasibility of local injections of microfragmented adipose tissue in patients with refractory complex fistulizing perianal Crohn's disease (PCD) were evaluated., Methods: Fifteen patients with persistent complex fistulizing PCD after biosurgical approach and subsequent surgical "rescue" repair were treated in S. Orsola-Malpighi Hospital with a single-local administration of microfragmented adipose tissue prepared using a minimal manipulation technique (Lipogems) in a closed system. Clinical outcomes were determined at 24-week follow-ups assessing success rate, defined as combined clinical and radiological remission., Results: Upon clinical examination at 24 weeks, 10 patients had combined remission (clinical and radiographic), 4 patients showed improvements, and 1 patient failed. The results were confirmed in all patients by pelvic MRI. No relevant postoperative complications nor adverse events were reported., Conclusion: These results suggest that the local injection of autologous microfragmented adipose tissue is a safe and promising "rescue therapy" for patients with multiresistant complex fistulizing PCD. This approach might be proposed as routine because it is affordable, is minimally invasive, has no risk of sphincteric damage, and can be carried out in a day-surgery setting., (© 2019 Crohn’s & Colitis Foundation. Published by Oxford University Press on behalf of Crohn’s & Colitis Foundation.)