In 2001, researchers at the University of California, Los Angeles, described the isolation of a new population of adult stem cells from liposuctioned adipose tissue. These stem cells, now known as adipose-derived stem cells or ADSCs, have gone on to become one of the most popular adult stem cells populations in the fields of stem cell research and regenerative medicine. As of today, thousands of research and clinical articles have been published using ASCs, describing their possible pluripotency in vitro, their uses in regenerative animal models, and their application to the clinic. This paper outlines the progress made in the ASC field since their initial description in 2001, describing their mesodermal, ectodermal, and endodermal potentials both in vitro and in vivo, their use in mediating inflammation and vascularization during tissue regeneration, and their potential for reprogramming into induced pluripotent cells.

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Adipose-Derived Stem Cells in Tissue Regeneration: A Review

Human skin is a remarkable organ that sustains insult and injury throughout life. The ability of skin to expeditiously repair wounds is paramount to survival. With an aging global population, coupled with a rise in the prevalence of conditions such as diabetes, chronic wounds represent a significant biomedical burden. Mesenchymal stem cells (MSC), a progenitor cell population of the mesoderm lineage, have been shown to be significant mediators in inflammatory environments. Preclinical studies of MSC in various animal wound healing models point towards a putative therapy. This review examines the body of evidence suggesting that MSC accelerate wound healing in both clinical and preclinical studies and also the possible mechanisms controlling its efficacy. The delivery of a cellular therapy to the masses presents many challenges from a safety, ethical, and regulatory point of view. Some of the issues surrounding the introduction of MSC as a medicinal product are also delineated in this review.

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Mesenchymal Stem Cells and Cutaneous Wound Healing: Current Evidence and Future Potential.

Hypoxia enhances the proliferation and migration of adipose-derived stem cells (ASCs) via the generation of reactive oxygen species (ROS). Therefore, this study primarily investigated whether or not ROS generation could regulate microRNA-210 (miR-210) expression, and increase proliferation/migration of ASCs. In addition, we tried to identify the signaling pathways involved in miR-210 upregulation and the direct target genes of miR-210 that mediate these functions. Various sources of ROS generation such as hypoxia, antimycin, rotenone, and platelet-derived growth factor (PDGF)-BB upregulated miR-210 expression, and increased the proliferation/migration of ASCs. There is a positive feed-forward loop between ROS generation and miR-210, and miR-210 itself increases ROS generation by downregulation of iron–sulfur cluster scaffold homolog 2 (ISCU2). Although hypoxia-inducible factor-1α was not involved in miR-210 expression, pharmacological or small interfering RNA (siRNA)-driven inhibition of Akt and ERK1/2 molecules reduced miR-210 expression. Transfection of siRNAs of NF-κB and Elk1 also reduced miR-210 expression, indicating that these signaling pathways mediate miR-210 upregulation. Protein tyrosine phosphatase, non-receptor type 2 (PTPN2) was selected for miR-210 target gene, and it was downregulated by ROS generators or miR-210 mimic treatment. PTPN2 was first proven to be a direct miR-210 target in luciferase activity assay, and pharmacological inhibition or overexpression of PTPN2 regulated the proliferation and migration of ASC. In conclusion, ROS generation from diverse sources induces miR-210 expression in ASCs via PDGFR-β, Akt and ERK pathways. Transcription of miR-210 expression is regulated by NF-κB and Elk1, and miR-210 increases the proliferation and migration of ASCs via ISCU2 and PTPN2 downregulation.

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Reactive oxygen species-responsive miR-210 regulates proliferation and migration of adipose-derived stem cells via PTPN2.

Functionalized self-assembling peptide nanofiber hydrogels mimic stem cell niche to control human adipose stem cell behavior in vitro

Significance: With an aging population leading to an increase in diabetes and associated cutaneous wounds, there is a pressing clinical need to improve wound-healing therapies. Recent Advances: Tissue engineering approaches for wound healing and skin regeneration have been developed over the past few decades. A review of current literature has identified common themes and strategies that are proving successful within the field: The delivery of cells, mainly mesenchymal stem cells, within scaffolds of the native matrix is one such strategy. We overview these approaches and give insights into mechanisms that aid wound healing in different clinical scenarios. Critical Issues: We discuss the importance of the biomimetic niche, and how recapitulating elements of the native microenvironment of cells can help direct cell behavior and fate. Future Directions: It is crucial that during the continued development of tissue engineering in wound repair, there is close collaboration between tissue engineers and clinici...

Current Advancements and Strategies in Tissue Engineering for Wound Healing: A Comprehensive Review.

Skin flaps are frequently performed for diabetic patients in spite of countless detrimental effects of diabetes on flap survival, most of which may result from a defective response of the tissues to low oxygen tension. In this study, the authors explored the feasibility of applying human adipose-derived stem cells (ASCs) to increase the viability of random-patterned skin flaps in streptozotocin-induced diabetic mice. ASCs were isolated from the fresh human lipoaspirates and expanded ex vivo for three passages. After the elevation of caudally based random-patterned skin flaps (3 cm long and 1 cm wide), ASCs suspensions were then injected into the flap (group A). Media containing no ASCs were similarly injected as a control (group B), although nothing was injected into the flap base of mice in control group C. Flap assessments were carried out at post-operative day 7 for evaluation of flap viability. The flap survival rate of group A was significantly higher than those of groups B and C, whereas no difference was observed between groups B and C. Histological examination also demonstrated a statistically significant increase in capillary density in group A over both groups B and C. Furthermore, it was found that ASCs not only augmented the expression of vascular endothelial growth factor and hypoxia-inducible factor-1α (HIF-1α) in flap tissues from dermis of diabetes mice, but also promoted their expression in dermal fibroblasts from diabetic mice. Thus, ASCs could enhance the survival of random-patterned skin flaps in streptozotocin-induced diabetic mice via elevated expression of HIF-1α.

https://onlinelibrary.wiley.com/doi/pdf/10.1111/j.1582-4934.2011.01313.x

Adipose-derived stem cells accelerate neovascularization in ischaemic diabetic skin flap via expression of hypoxia-inducible factor-1α

Contribution of skin trauma to infantile skin hemangioma

Objective
To investigate whether administrating Abnormal Savda Munziq (ASMq), a traditional Uighur herbal preparation used for the prevention or treatment of diseases, affects hypertrophic scar (HTS) formation by using an established rabbit ear model.

Effect of Abnormal Savda Munziq on hypertrophic scar formation in a rabbit ear model.

Objective To evaluate in vitro effect of abnormal savda munziq (ASMq) on the proliferation and apoptosis of human hypertrophic scar fibroblasts (HSFs).Methods HSFs were divided into six groups to receive different treatments as group A (blank control group),group B-E (ASMq in different concentration),and group F(5-Fu).Each group contains six specimens.The HSFs were cultured in vitro.After culture for 48 hours,The CCK8 test and flow cytometry methods were used to detect the proliferation,cell cycle and apoptosis.Results The proliferation of HSFs in the B,C,D and E groups was inhibited at G2/M period,while it was inhibited at G0/S period in group F(P ＜ 0.05).The inhibition effect of ASMq(0.1 ～ 1.0 mg/ml) on the fibroblasts enhanced in a concentration-dependent manner.Flow cytometry analysis with annexin V-FITC and PI staining confirmed the apoptotic.When HSFs were exposed to ASMq at 1.0 mg/ml (group E) for 48 h,the percentage of apoptotic cells increased to (43.7 ± 2.58) ％,which was significantly higher than that of blank control group (2.2 ± 0.59) ％.The induced apoptosis effect was also increased in a concentration-dependent manner.Conclusion ASMq has a inhibitory effect on the proliferation and an enhancement effect on the apoptosis of fibroblast.ASMq could be used as an effective drug for treatment of hypertrophic scar.

Key words: 
Abnormal Savda Munziq;  Fibroblast;  Apoptosis

Weicheng Gao

Papers

Adipose-derived stem cells accelerate neovascularization in ischaemic diabetic skin flap via expression of hypoxia-inducible factor-1α

Contribution of skin trauma to infantile skin hemangioma

Effect of Abnormal Savda Munziq on hypertrophic scar formation in a rabbit ear model.

Effect of uighur medicine abnormal savda munzip on human hypertrophic scar fibroblasts in vitro

Massage can facilitate soft tissue expansion