Schwann cell-like cells (SCLCs), differentiated from mesenchymal stem cells, have shown promising outcomes in the treatment of peripheral nerve injuries in preclinical studies. However, certain clinical obstacles limit their application. Hence, the primary aim of this study was to investigate the role of exosomes derived from SCLCs (SCLCs-exo) in peripheral nerve regeneration. SCLCs were differentiated from human amniotic mesenchymal stem cells (hAMSCs) in vitro and validated by immunofluorescence, real-time quantitative PCR and western blot analysis. Exosomes derived from hAMSCs (hAMSCs-exo) and SCLCs were isolated by ultracentrifugation and validated by nanoparticle tracking analysis, WB analysis and electron microscopy. A prefabricated nerve graft was used to deliver hAMSCs-exo or SCLCs-exo in an injured sciatic nerve rat model. The effects of hAMSCs-exo or SCLCs-exo on rat peripheral nerve injury (PNI) regeneration were determined based on the recovery of neurological function and histomorphometric variation. The effects of hAMSCs-exo or SCLCs-exo on Schwann cells were also determined via cell proliferation and migration assessment. SCLCs significantly expressed the Schwann cell markers glial fibrillary acidic protein and S100. Compared to hAMSCs-exo, SCLCs-exo significantly enhanced motor function recovery, attenuated gastrocnemius muscle atrophy and facilitated axonal regrowth, myelin formation and angiogenesis in the rat model. Furthermore, hAMSCs-exo and SCLCs-exo were efficiently absorbed by Schwann cells. However, compared to hAMSCs-exo, SCLCs-exo significantly promoted the proliferation and migration of Schwann cells. SCLCs-exo also significantly upregulated the expression of a glial cell-derived neurotrophic factor, myelin positive regulators (SRY-box transcription factor 10, early growth response protein 2 and organic cation/carnitine transporter 6) and myelin proteins (myelin basic protein and myelin protein zero) in Schwann cells. These findings suggest that SCLCs-exo can more efficiently promote PNI regeneration than hAMSCs-exo and are a potentially novel therapeutic approach for treating PNI.

The cutaneous lymphatic system regulates tissue inflammation, fluid balance and immunological responses. Lymphangiogenesis or lymphatic dysfunction may lead to lymphedema, immune deficiency, chronic inflammation etc. Tissue regeneration and healing depend on angiogenesis and lymphangiogenesis during wound healing. Tissue oedema and chronic inflammation can slow wound healing due to impaired lymphangiogenesis or lymphatic dysfunction. For example, impaired lymphangiogenesis or lymphatic dysfunction has been detected in nonhealing wounds such as diabetic ulcers, venous ulcers and bedsores. This review summarizes the structure and function of the cutaneous lymphatic vessel system and lymphangiogenesis in wounds. Furthermore, we review wound lymphangiogenesis processes and remodelling, especially the influence of the inflammatory phase. Finally, we outline how to control lymphangiogenesis to promote wound healing, assess the possibility of targeting lymphangiogenesis as a novel treatment strategy for chronic wounds and provide an analysis of the possible problems that need to be addressed.

Mesenchymal stem cells (MSCs) possess a capacity to enhance cutaneous wound healing that is well characterized. However, the therapeutic effect of MSCs appears to be limited. Modifying MSC target genes to increase necessary biological effects is a promising strategy for wound therapy. Interleukin-10 (IL-10) is an anti-inflammatory cytokine that has a therapeutic effect on wound healing. In this study, we modified human amniotic mesenchymal stem cells (hAMSCs) using recombinant lentiviral vectors for expressing IL-10 and evaluated the therapeutic effects of hAMSCs-IL-10 in wound healing. We elucidated the mechanisms underlying the effects. We found that promoting wound healing was maintained by synergistic effects of hAMSCs and IL-10. hAMSCs-IL-10 showed stronger biological effects in accelerating wound closure, enhancing angiogenesis, modulating inflammation, and regulating extracellular matrix remodeling than hAMSCs. hAMSCs-IL-10 would be better at promoting wound healing and improving healing quality. These data may provide a theoretical foundation for clinical administration of hAMSCs-IL-10 in cutaneous wound healing and skin regeneration.

Adipose-derived stem cell- (ADSC-) based regenerative medicine has expanded to include the treatment of hair loss. However, stem cell therapy remains a relatively recent technique, and reports of its use for treating alopecia are rare. ADSCs exert biological functions via the paracrine actions of various growth factors and cytokines. Conditioned medium from ADSCs (ADSCs-CM) is a cell-free suspension rich in growth factors and cytokines that has demonstrated a significant role in stimulating hair growth, with encouraging outcomes in terms of hair regeneration and hair growth. Extracellular matrix/stromal vascular fraction gel (ECM/SVF-gel) is an ADSC- and adipose native extracellular matrix-enriched product for cytotherapy. In this study, we compared the effects of CM from ECM/SVF-gel (ECM/SVF-CM) and from stem cells (SVF-CM) on hair growth in mice. ECM/SVF-CM stimulated hair growth more than SVF-CM, through promoting the proliferation of dermal papilla cells and cells in the bulge, neovascularization, and anagen induction. ECM/SVF-CM might, thus, provide an effective and improved strategy for promoting hair growth. These data provide a theoretical foundation for the clinical administration of ECM/SVF-CM for the treatment of hair loss.

Background: Chronic refractory wounds easily relapse and seriously affect the patients’ quality of life. Previous studies have shown that stromal vascular fraction gel (SVF-gel) significantly promotes the early healing of chronic wounds; however, the mechanisms of SVF-gel function per se remain unclear, and a long-term follow-up is lacking. This study aims to explore the mechanisms of SVF-gel promoting the healing of chronic wounds and follow up the long-term efficacy of SVF-gel. Methods: Autologous SVF-gel transplantation was performed in 20 patients with chronic wounds (from March 2016 to September 2019), and the size of the wound before and after SVF-gel transplantation was observed. The conditioned medium (CM) was harvested from SVF-gel under serum-free, serum-deprivation and 10% fetal bovine serum (FBS) microenvironment in vitro, respectively. The concentration of the growth factors in the two kinds of gel-CM was tested, and their effects on the proliferation and migration of human dermal fibroblasts (HDFs) were detected. Results: All patients had 100% wound closure eventually, and the average time to complete closure was 28.3 ± 9.7 days. The time of follow-up ranged from 2 to 6 years, and there was no wound recurrence. Interestingly, the concentrations of epidermal growth factor and transforming growth factor β1 of the CM were higher in serum-free and serum-deprivation condition than in 10% FBS microenvironment (p < 0.05). Correspondingly, the proliferation and migration ability of HDFs treated with gel-CM from serum-free condition were stronger than those treated with gel-CM from serum-deprivation (2% FBS) or 10% FBS microenvironment (p < 0.05). Conclusion: These results indicate that it is safe, effective, and lasting in effect to treat chronic wounds with SVF-gel and mechanisms of action that include secreting various cytokines and promoting cell proliferation and migration ability. Trial registration: Chinese Clinical Trail Registry, ChiCTR2000034624. Registered 12 July 2020—Retrospectively registered, http://www.chictr.org.cn/showproj.aspx?proj=56058

Background: Diabetic foot ulcer (DFU) is frequently difficult to heal and finally leads to amputation, resulting in high mortality rate in diabetic patients. To date, effective and optimal therapies are still lacking. This study aims to investigate the efficacy of integrated surgical wound treatment (ISWT) mode on diabetic foot wound.Methods: From January 2021 to December 2021, 13 diabetic foot patients with Wagner grade 3 to 4 were treated with ISWT mode, which combined TTT technique with debridement, induced membrane technique, vacuum sealing drainage (VSD) technique and skin grafting technique. The time of wound healing, the skin temperature at midpoint of dorsum of affected foot (T), visual analogue scale (VAS) score and ankle-brachial index (ABI) was measured before and after surgery. CTA examination of the lower extremity arteries was performed at the end of the cortex transport to evaluate the small arteriolar formation of the lower extremity. The complications occurred in each patient were recorded.Results: 13 patients with age ranging from 45 to 66 years were followed up for 3 to 13 months. All patients healed completely without amputation being performed, no serious complications were found except for one case of nail channel infection. The mean healing time was 25.8 ± 7.8 days, with a range of 17 to 39 days. The mean time of carrying external fixation scaffolds and resuming walking was 71.8 ± 10.0 and 30.8 ± 9.1 days, with a range of 56 to 91 days and 18 to 45 days, respectively. The skin temperature at midpoint of dorsum of affected foot (T), VAS and ABI was all improved significantly at 3 months after surgery. Furthermore, CTA examination showed an increase in the number of lower extremity arteries and a thickening in the size of small arteriolar compared with those of pre-operative, and the collateral circulation of lower extremity was established and interweaved into a network.Conclusion: Integrated surgical treatment of diabetic foot wound can achieve satisfactory clinical results.