Apoptotic vesicles inherit SOX2 from pluripotent stem cells to accelerate wound healing by energizing mesenchymal stem cells

Yan Qu; Yifan He; Bowen Meng; Xiao Zhang; Junjun Ding; Xiaoxing Kou; Wei Teng; Songtao Shi

doi:10.1016/j.actbio.2022.07.009

Apoptotic vesicles inherit SOX2 from pluripotent stem cells to accelerate wound healing by energizing mesenchymal stem cells

Acta Biomater. 2022 Sep 1:149:258-272. doi: 10.1016/j.actbio.2022.07.009. Epub 2022 Jul 10.

Authors

Yan Qu¹, Yifan He¹, Bowen Meng¹, Xiao Zhang², Junjun Ding³, Xiaoxing Kou⁴, Wei Teng⁵, Songtao Shi⁶

Affiliations

¹ Hospital of Stomatology, Guanghua School of Stomatology, Sun Yat-sen University, South China Center of Craniofacial Stem Cell Research, Guangdong Provincial Key Laboratory of Stomatology, 510055, Guangzhou, China.
² Department of Prosthodontics, Peking University School and Hospital of Stomatology, National Laboratory for Digital and Material Technology of Stomatology, Beijing Key Laboratory of Digital Stomatology, National Clinical Research Center for Oral Diseases, Beijing 100081, China.
³ Department of Cell Biology, Zhongshan School of Medicine, Sun Yat-Sen University, Guangzhou 510080, China.
⁴ Hospital of Stomatology, Guanghua School of Stomatology, Sun Yat-sen University, South China Center of Craniofacial Stem Cell Research, Guangdong Provincial Key Laboratory of Stomatology, 510055, Guangzhou, China; Key Laboratory of Stem Cells and Tissue Engineering, Sun Yat-Sen University, Ministry of Education, Guangzhou 510080, China.
⁵ Hospital of Stomatology, Guanghua School of Stomatology, Sun Yat-sen University, Guangdong Provincial Key Laboratory of Stomatology, Guangzhou 510055, China. Electronic address: tengwei@mail.sysu.edu.cn.
⁶ Hospital of Stomatology, Guanghua School of Stomatology, Sun Yat-sen University, South China Center of Craniofacial Stem Cell Research, Guangdong Provincial Key Laboratory of Stomatology, 510055, Guangzhou, China; Key Laboratory of Stem Cells and Tissue Engineering, Sun Yat-Sen University, Ministry of Education, Guangzhou 510080, China. Electronic address: shisongtao@mail.sysu.edu.cn.

PMID: 35830925
DOI: 10.1016/j.actbio.2022.07.009

Abstract

Billions of cells undergo apoptosis every day in the human body, resulting in the generation of a large number of apoptotic vesicles (apoVs) to maintain organ and tissue homeostasis. However, the characteristics and function of pluripotent stem cell (PSC)-derived apoVs (PSC-apoVs) are largely unknown. In this study, we showed that human embryonic stem cells (ESCs) and induced pluripotent stem cells (iPSCs) produced larger numbers of apoVs than human umbilical cord mesenchymal stem cells (UMSCs) do when induced by staurosporine. In addition to expressing the general apoV markers cleaved caspase 3, Annexin V, calreticulin, ALIX, CD63 and TSG101, ESC-apoVs inherited pluripotent-specific molecules SOX2 from ESCs in a caspase 3-dependent manner. Moreover, ESC-apoVs could promote mouse skin wound healing via transferring SOX2 into skin MSCs via activating Hippo signaling pathway. Collectively, these findings reveal that apoVs are capable of inheriting pluripotent molecules from ESCs to energize adult stem cells, suggesting the potential to use PSC-apoVs for clinical applications. STATEMENT OF SIGNIFICANCE: Apoptotic vesicles (apoVs) are essential to maintain organ and tissue homeostasis. However, the characteristics and function of pluripotent stem cell (PSC)-derived apoVs (PSC-apoVs) are largely unknown. This study showed that PSC-apoVs produced 100 times more apoVs than human umbilical cord mesenchymal stem cells (UMSCs). Despite expressing the general apoV makers, PSC-apoVs inherited pluripotent-specific molecule SOX2 from PSCs in a caspase 3-dependent manner. Moreover, PSC-apoVs promote mouse skin wound healing via transferring SOX2 into skin MSCs, thus activating Hippo signaling pathway. These findings reveal that apoVs are capable of inheriting pluripotent molecules from PSCs to energize adult stem cells, thus providing a cell-free strategy for clinical applications of PSCs.

Keywords: Apoptotic vesicles; Hippo signaling pathway; Mesenchymal stem cells; Pluripotent stem cell; Wound healing.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Animals
Caspase 3 / metabolism
Cell Differentiation / physiology
Humans
Induced Pluripotent Stem Cells* / metabolism
Mesenchymal Stem Cells* / metabolism
Mice
Pluripotent Stem Cells*
SOXB1 Transcription Factors / metabolism
Wound Healing

Substances

SOX2 protein, human
SOXB1 Transcription Factors
Sox2 protein, mouse
Caspase 3