2. Academic Validation
  3. Conditioned medium from induced pluripotent stem cell-derived mesenchymal stem cells accelerates cutaneous wound healing through enhanced angiogenesis

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

  • Stem Cell Res Ther. 2021 May 20;12(1):295. doi: 10.1186/s13287-021-02366-x.
Xiaoting Liang  # 1 2,  Fang Lin  # 2 3,  Yue Ding 4,  Yuelin Zhang 5,  Mimi Li 2,  Xiaohui Zhou 2,  Qingshu Meng 2,  Xiaoxue Ma 2,  Lu Wei 2,  Huimin Fan 6,  Zhongmin Liu 7 8 9
Affiliations

Affiliations

  • 1 Institute for Regenerative Medicine, Shanghai East Hospital, School of Life Sciences and Technology, Tongji University, Shanghai, People's Republic of China.
  • 2 Research Center for Translational Medicine, Shanghai East Hospital, School of Medicine, Tongji University, Shanghai, People's Republic of China.
  • 3 Laboratory of Arrhythmias, Ministry of Education of China, Shanghai East Hospital, Tongji University, Shanghai, People's Republic of China.
  • 4 Department of Organ Transplantation, Changzheng Hospital, Second Military Medical University, Shanghai, People's Republic of China.
  • 5 Department of Emergency, Guangdong General Hospital, Guangdong Academy of Medical Science, Guangzhou, People's Republic of China.
  • 6 Research Center for Translational Medicine, Shanghai East Hospital, School of Medicine, Tongji University, Shanghai, People's Republic of China. frankfan@tongji.edu.cn.
  • 7 Institute for Regenerative Medicine, Shanghai East Hospital, School of Life Sciences and Technology, Tongji University, Shanghai, People's Republic of China. liu.zhongmin@tongji.edu.cn.
  • 8 Research Center for Translational Medicine, Shanghai East Hospital, School of Medicine, Tongji University, Shanghai, People's Republic of China. liu.zhongmin@tongji.edu.cn.
  • 9 Department of Cardiovascular Surgery, Shanghai East Hospital, Tongji University, Shanghai, People's Republic of China. liu.zhongmin@tongji.edu.cn.
  • # Contributed equally.
PMID: 34016178 DOI: 10.1186/s13287-021-02366-x
Abstract

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 H2O2-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 H2O2 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 H2O2-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.

Keywords

Conditioned medium; Induced pluripotent stem cell-derived mesenchymal stem cells; Mitochondria dysfunction; Wound healing.

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