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Adipose tissue-derived mesenchymal stem are adult stem cells endowed with multipotent abilities and immunomodulatory properties, like mesenchymal stem cells of other origins. Numerous studies show that adipose tissue stem cells are involved in the pathological process and can exhibit pro-inflammatory properties and attract inflammatory immune cells in the neighborhood. Subsequently, inflammation creates a microenvironment leading to adipose tissue dysfunction. Examples of such a process are obesity and type 2 diabetes mellitus, in which adipogenesis is disrupted and insulin resistance is initiated. The aim of this review is to understand the role of adipose tissue stem cells in the pathogenesis of obesity and type 2 diabetes mellitus.

Aim: The aim of this study was to systematically review the applications of adipose tissue stem cells (ADSCs) in regenerative dentistry. Materials and Methods: An M electronic search was conducted in Medline (PubMed) and Scopus databases. The original research associated with the role of ADSCs in regeneration of alveolar bone, periodontal ligament (PDL), cementum as well as the dental pulp was evaluated. Among the included studies, three animal studies and one human study had low risk of bias. Results: A total of 33 relevant studies were included in the review. The animal models, in vivo human, and in vitro studies revealed that ADSCs had a significant osteogenic differentiation potential. Besides, they had potential to differentiate into PDL, cementum, and dental pulp tissue. Conclusion: The ADSCs may be specifically applied for bone tissue engineering in the management of alveolar bone defects, specifically in dental implants and periodontal disease. However, their role in regeneration of PDL, cementum, and dental pulp requires further investigations. Overall, their applications in regenerative dentistry needs further verification through human clinical trials. [ABSTRACT FROM AUTHOR]

Abstract Background A randomized controlled trial (RCT) was performed to confirm preliminary uncontrolled data indicating that regional adipose tissue (AT) grafting (G) is effective in inducing ischemic digital ulcer (IDU) healing in patients with systemic sclerosis (SSc). Patients and methods SSc patients with IDUs were randomized to be blindly treated with AT-G or a sham procedure (SP). AT-G consisted of injection, at the base of the finger with the IDU, of 0.5–1 ml AT after centrifugation of fat aspirate. The SP consisted of false liposuction and local injection of saline solution. The primary endpoint was to compare the cumulative prevalence of healed IDUs in the two groups within the following 8 weeks. Results AT-G and the SP were carried out in 25 and 13 patients, respectively. The two groups were comparable for age, gender, disease duration, and SSc subtypes. IDU healing was observed in 23/25 and 1/13 patients treated with AT-G and the SP, respectively (p

Background/Aims: Pericytes (PCs) are multipotent vascular precursors that play a critical physiological role in the development and maintenance of blood vessel integrity. In this study, we aim to characterize PCs isolated from human abdominal adipose tissue and develop an integration-free induced pluripotent stem cells (iPSCs) using episomal vectors. Methods: The ultrastructure of adipose tissue-derived PCs was determined using scanning and transmission electron microscopy. The expression of mesenchymal stem cells (MSCs) and pericyte markers were examined using flow cytometry and PCR analysis. PCs were induced to adipogenic, osteogenic and myogenic lineages, and their angiogenic potential was determined using tube formation assay. We further established pericyte reprogramming protocol using episomal vectors. Results: Our data showed that human adipose tissue-derived PCs uniformly expressed MSCs, CD105 and CD73, and PCs markers, desmin, and alpha smooth muscle actin (α-SMA), while lacked the expression of HLA-DR and the hematopoietic markers CD34, CD11b and CD45. Ultrastructure analysis showed typical internal structure for the PCs with a characteristic prominent eccentric nuclei and cytoplasmic invaginations forming a caveolar system. Functional analysis showed efficient differentiation into adipocytes, osteocytes, and myocytelike cells. Adipose tissue-derived PCs showed angiogenic potential using tube-forming assay. To determine further application of these cells for personalized therapy, we reprogrammed PCs into induced pluripotent stem cells (iPSCs) using episomal vectors. Reprogrammed cells gradually lost their fusiform shape, acquired the epithelial cell morphology and formed colonies. Furthermore, reprogrammed cells successfully expressed the pluripotency markers OCT4, Nanog, SSEA-4, and β-catenin, an early reprogramming marker. Conclusion: The accessibility and abundance of human fat supports the application of adipose derived PCs as a novel and promising source of cell therapy and regenerative medicine. [ABSTRACT FROM AUTHOR]

Adipose tissue-derived stem cells (ADSCs) are mesenchymal cells with the capacity for self-renewal and multipotential differentiation. This multipotentiality allows them to become adipocytes, chondrocytes, myocytes, osteoblasts and neurocytes among other cell lineages. Stem cells and, in particular, adipose tissue-derived cells, play a key role in reconstructive or tissue engineering medicine as they have already proven effective in developing new treatments. The purpose of this work is to review the applications of ADSCs in various areas of regenerative medicine, as well as some of the risks associated with treatment with ADSCs in neoplastic disease. [ABSTRACT FROM AUTHOR]

Articular cartilage is affected by weight loading and mechanical stimuli. Low intensity ultrasound promotes chondrogenesis in cartilage injury. This study was designed to show the effect of low-intensity pulsed ultrasound on chondrogenesis potential of transplanted adipose derived stem cells- polycaprolactone (ASCs –PCL) construct in vivo.The adipose tissue was obtained from infrapatellar fat pad of 5 male sheep. Adipose tissue derived stem cells (ASCs) at passage 2 were seeded in polycaprolactone (PCL). The cartilage defects were created on both sides of distal femoral articular cartilage. The right joint was chosen as control group. The left joint was chosen as experimental group and was exposed to low-intensity pulsed ultrasound with intensity 200 mW/cm², 10 min/day for 6 weeks. After 6 months, animals were euthanized to retrieve repaired articular cartilage tissue. Macroscopic appearance of defects was examined and samples of repaired cartilage tissue were analyzed by real time RT-PCR. The results showed that in the treated group with-LIPUS, cartilage defects were totally filled with relatively thin amorphous proliferative tissue and in the control group the defects were left as a dimple in the cartilage defects. Real time RT-PCR analysis showed that cartilage-specific genes expression levels are significantly increased by application of LIPUS after transplantation of ASCs-PCL construct in vivo. The results suggested that low-intensity pulsed ultrasound stimulates ASCs differentiation and induces chondrogenesis at the ASCs-PCL construct in in vivo.

Articular cartilage is affected by weight loading and mechanical stimuli. Low intensity ultrasound promotes chondrogenesis in cartilage injury. This study was designed to show the effect of low-intensity pulsed ultrasound on chondrogenesis potential of transplanted adipose derived stem cells- polycaprolactone (ASCs -PCL) construct in vivo.The adipose tissue was obtained from infrapatellar fat pad of 5 male sheep. Adipose tissue derived stem cells (ASCs) at passage 2 were seeded in polycaprolactone (PCL). The cartilage defects were created on both sides of distal femoral articular cartilage. The right joint was chosen as control group. The left joint was chosen as experimental group and was exposed to low-intensity pulsed ultrasound with intensity 200 mW/cm2, 10 min/day for 6 weeks. After 6 months, animals were euthanized to retrieve repaired articular cartilage tissue. Macroscopic appearance of defects was examined and samples of repaired cartilage tissue were analyzed by real time RT-PCR. The results showed that in the treated group with-LIPUS, cartilage defects were totally filled with relatively thin amorphous proliferative tissue and in the control group the defects were left as a dimple in the cartilage defects. Real time RT-PCR analysis showed that cartilage-specific genes expression levels are significantly increased by application of LIPUS after transplantation of ASCs-PCL construct in vivo. The results suggested that low-intensity pulsed ultrasound stimulates ASCs differentiation and induces chondrogenesis at the ASCs-PCL construct in in vivo. [ABSTRACT FROM AUTHOR]

We previously reported that adipose tissue could generate cardiomyocyte-like cells from crude stromal vascular fraction (SVF) in vitro that improved cardiac function in a myocardial infarction context. However, it is not clear whether these adipose-derived cardiomyogenic cells (AD-CMG) constitute a homogenous population and if AD-CMG progenitors could be isolated as a pure population from the SVF of adipose tissue. This study aims to characterize the different cell types that constitute myogenic clusters and identify the earliest AD-CMG progenitors in vitro for establishing a complete phenotype and use it to sort AD-CMG progenitors from crude SVF. Here, we report cell heterogeneity among adipose-derived clusters during their course of maturation and highlighted sub-populations that exhibit original mixed cardiac/skeletal muscle phenotypes with a progressive loss of cardiac phenotype with time in liquid culture conditions. Moreover, we completed the phenotype of AD-CMG progenitors but we failed to sort them from the stromal vascular fraction. We demonstrated that micro-environment is required for the maturation of myogenic phenotype by co-culture experiments. These findings bring complementary data on AD-CMG and suggest that their emergence results from in vitro events.

Cardiovascular diseases are the number one cause of death globally and are projected to remain the single leading cause of death. Treatment options abounds, although efficacy is limited. Recent studies attribute discrete and ephemeral benefits to adult stem cell therapies, indicating the urge to improve stem cell based-therapy. In this study, we show that priming mesenchymal stem cells ( MSC) towards cardiomyogenic lineage enhances their beneficial effects in vivo as treatment option for acute phase myocardial infarction. MSC were primed using cardiomyogenic media for 4 days, after which peak expression of key cardiomyogenic genes are reached and protein expression of Cx-43 and sarcomeric α-actinin are observed. MSC and primed MSC ( pMSC) were characterized in vitro and used to treat infarcted rats immediately after left anterior descending ( LAD) occlusion. Echocardiography analysis indicated that MSC-treated myocardium presented discrete improvement in function, but it also showed that pMSC treatment lead to superior beneficial results, compared with undifferentiated MSC. Seven days after cell injection, MSC and pMSC could still be detected in the myocardium. Connexin-43 expression was quantified through immunoblotting, and was superior in pMSC, indicating that this could be a possible explanation for the superior performance of pMSC therapy. [ABSTRACT FROM AUTHOR]

The success of cell replacement therapy for diabetes depends on the availability and generation of an adequate number of islets, preferably from an autologous origin. Stem cells are now being probed for the generation of physiologically competent, insulin-producing cells. In this investigation, we explored the potential of adipose tissuederived stem cells (ASCs) to differentiate into pancreatic hormone-expressing islet-like cell aggregates (ICAs). We initiated ASC culture from epididymal fat pads of Swiss albino mice to obtain mesenchymal cells, murine epididymal (mE)-ASCs. Subsequent single-cell cloning resulted in a homogeneous cell population with a CD29+CD44+Sca-1+ surface antigen expression profile. We formulated a 10- day differentiation protocol to generate insulin-expressing ICAs from mE-ASCs by progressively changing the differentiation cocktail on day 1, day 3, and day 5. Our stagespecific approach successfully differentiated mesodermic mE-ASCs into definitive endoderm (cells expressing Sox17, Foxa2, GATA-4, and cytokeratin [CK]-19), then into pancreatic endoderm (cells expressing pancreatic and duodenal homeobox [PDX]-1, Ngn3, NeuroD, Pax4, and glucose transporter 2), and finally into cells expressing pancreatic hormones (insulin, glucagon, somatostatin). Fluorescenceactivated cell sorting analysis showed that day 5 ICAs contained 64.84% ± 7.03% PDX-1+ cells, and in day 10 mature ICAs, 48.17% ± 3% of cells expressed C-peptide. Day 10 ICAs released C-peptide in a glucose-dependent manner, exhibiting in vitro functionality. Electron microscopy of day 10 ICAs revealed the presence of numerous secretory granules within the cell cytoplasm. Calcium alginate- encapsulated day 10 ICAs (1,000-1,200), when transplanted i.p. into streptozotocin-induced diabetic mice, restored normoglycemia within 2 weeks. The data presented here demonstrate the feasibility of using ASCs as a source of autologous stem cells to differentiate into the pancreatic lineage. [ABSTRACT FROM AUTHOR]

Introduction: Drug-induced liver injury (DILI) is a leading cause of acute liver injury (ALI). Acetaminophen (also termed paracetamol), can often be found in drugs that may be abused (i.e., prescription for pain relief). Animal experiments have shown that mesenchymal stem cell transplantation can ameliorate or even reverse hepatic injury., Material and Methods: ALI was induced in Wistar rats using paracetamol. ATSCs were transplanted via the intravenous, portal vein, or intrahepatic route directly onto the liver parenchyma. Histological evaluation was conducted to assess drug-induced injury following transplantation. Fluorescence in situ hybridization (FISH) was used to verify the location of stem cells on the liver parenchyma. The effect of those cells on liver regeneration was tested by immunohistochemistry for hepatic growth factor (HGF). In addition, reverse transcription-quantitative PCR (qRT-PCR) was used to assess hepatic growth factor (HGF), hepatic nuclear factor 4α (HNF4α), cytochrome P450 1A2 (CYP1A2) and α-fetoprotein (AFP) mRNA expression., Results: Immunohistochemical staining for HGF was stronger in the transplanted groups than that in the control group (P<0.001). HNF4α and HGF mRNA levels were increased on day 7 following transplantation (P<0.001 and P=0.009, respectively). CYP1A2 mRNA levels were also increased (P=0.013) in the intravenous groups, while AFP levels were higher in the intrahepatic groups (P=0.006). ATSC transplantation attenuates ALI injury and promotes liver regeneration. Furthermore, expression of specific hepatic enzymes points to ATSC hepatic differentiation., Conclusion: The study showed the positive effects of transplanted adipose tissue stem cells (ATSCs) on liver regeneration (LG) through hepatotrophic factors. Furthermore, increased expression of hepatic specific proteins was recorded in ATSC transplanted groups that indicate stem cells differentiation into hepatic cells., Competing Interests: None., (AJSC Copyright © 2020.)

Adipose tissue stem cells (ASCs), known as multipotent stem cells, are most commonly used in the clinical applications in recent years. Adipose tissues (AT) have the advantage in the harvesting, isolation, and expansion of ASCs, especially an abundant amount of stem cells compared to bone marrow. ASCs can be found in stromal vascular fractions (SVF) which are easily obtained from the dissociation of adipose tissue. Both SVFs and culture-expanded ASCs exhibit the stem cell characteristics such as differentiation into multiple cell types, regeneration, and immune regulators. Therefore, SVFs and ASCs have been researched to evaluate the safety and benefits for human use. In fact, the number of clinical trials on ASCs is going to increase by years; however, most trials are in phase I and II, and lack phase III and IV. This systemic review highlights and updates the process of the harvesting, characteristics, isolation, culture, storage, and application of ASCs, as well as provides further directions on the therapeutic use of ASCs. [ABSTRACT FROM AUTHOR]