Journal Article

Conditioned medium from induced pluripotent stem cell-derived mesenchymal stem cells accelerates cutaneous wound healing through enhanced angiogenesis

Ding, Yue, Ma, Xiaoxue, Fan, Huimin, Liu, Zhongmin, Meng, Qingshu, Lin, Fang, Liang, Xiaoting, Wei, Lu, Zhang, Yuelin, Li, Mimi, Zhou, Xiaohui

2021

Overview

Background Mesenchymal stem cells (MSCs) can improve cutaneous wound healing via the secretion of growth factors. However, the therapeutic efficacy of MSCs varies depending upon their source. Induced pluripotent stem cells are emerging as a promising source of MSCs with the potential to overcome several limitations of adult MSCs. This study compared the effectiveness of conditioned medium of MSCs derived from induced pluripotent stem cells (iMSC-CdM) with that derived from umbilical cord MSCs (uMSC-CdM) in a mouse cutaneous wound healing model. We also investigated the mechanisms of protection. Methods The iMSC-CdM or uMSC-CdM were topically applied to mice cutaneous wound model. The recovery rate, scar formation, inflammation and angiogenesis were measured. We compared angiogenesis cytokine expression between iMSC-CdM and uMSC-CdM and their protective effects on human umbilical vein endothelial cells (HUVECs) under H 2 O 2 -induced injury. The effects of iMSC-CdM on energy metabolism, mitochondria fragmentation and apoptosis were measured. Results Topical application of iMSC-CdM was superior to the uMSC-CdM in accelerating wound closure and enhancing angiogenesis. Expression levels of angiogenetic cytokines were higher in iMSC-CdM than they were in uMSC-CdM. The iMSC-CdM protected HUVECs from H 2 O 2 induced injury more effectively than uMSC-CdM did. Administration of iMSC-CdM stimulated HUVEC proliferation, tube formation and energy metabolism via the ERK pathway. Mechanistically, iMSC-CdM inhibited H 2 O 2 -induced mitochondrial fragmentation and apoptosis of HUVECs. Conclusion Collectively, these findings indicate that iMSC-CdM is more effective than uMSC-CdM in treating cutaneous wounds, and in this way, iMSC-CdM may serve as a more constant and sustainable source for cell-free therapeutic approach. Graphical abstract

• Publisher: BioMed Central,BioMed Central Ltd,Springer Nature B.V,BMC
• Subject: Angiogenesis / Apoptosis / Biomedical and Life Sciences / Biomedical Engineering and Bioengineering / Care and treatment / Cell Biology / Comparative analysis / Conditioned medium / Cotton / Cytokines / Endothelial cells / Energy metabolism / Epidermal growth factor / Fibroblasts / Gene expression / Growth factors / Health aspects / Hydrogen peroxide / Induced pluripotent stem cell-derived mesenchymal stem cells / Inflammation / Life Sciences / Mesenchymal stem cells / Metabolic pathways / Mitochondria / Mitochondria dysfunction / Physiological aspects / Pluripotency / Polymerase chain reaction / Proteins / Regenerative Medicine/Tissue Engineering / Respiration / Stem cell transplantation / Stem Cells / Topical application / Umbilical cord / Umbilical vein / Wound healing / Wounds and injuries