Targeting Programmed Cell Death to Improve Stem Cell Therapy: Implications for Treating Diabetes and Diabetes-Related Diseases.

Qi Zhang,Xin-Xing Wan,Wen-Juan Zhao,Wei-Tao Yan,Kun Xiong,Yan-Xia Huang,Xi-Min Hu,Xiao-Xia Ban

doi:10.3389/fcell.2021.809656

Abstract

Stem cell therapies have shown promising therapeutic effects in restoring damaged tissue and promoting functional repair in a wide range of human diseases. Generations of insulin-producing cells and pancreatic progenitors from stem cells are potential therapeutic methods for treating diabetes and diabetes-related diseases. However, accumulated evidence has demonstrated that multiple types of programmed cell death (PCD) existed in stem cells post-transplantation and compromise their therapeutic efficiency, including apoptosis, autophagy, necroptosis, pyroptosis, and ferroptosis. Understanding the molecular mechanisms in PCD during stem cell transplantation and targeting cell death signaling pathways are vital to successful stem cell therapies. In this review, we highlight the research advances in PCD mechanisms that guide the development of multiple strategies to prevent the loss of stem cells and discuss promising implications for improving stem cell therapy in diabetes and diabetes-related diseases.

Highlights

Stem cells (SCs) are unique cell populations distinguished by the capacity of self-renewal and differentiation (Biswas and Hutchins, 2007; McElhinney et al, 2020)
Extensive and increasing evidence demonstrates that distinct types of programmed cell death (PCD) contribute to the cell death of stem cells (SCs), and the inhibition of PCDs can promote the survival of SCs and their therapeutic effects in diabetes and diabetes-related diseases
These findings provide deep insights into the cell death of SCs-based therapy for diabetes and diabetes-related diseases and shed light on the future development of therapeutic strategies

Summary

Introduction

Stem cells (SCs) are unique cell populations distinguished by the capacity of self-renewal and differentiation (Biswas and Hutchins, 2007; McElhinney et al, 2020). The overexpression of Aurora kinase A (AURKA), a cell cycleregulated kinase, enhanced autophagy of ADSCs, decreased apoptosis, and promoted wound healing in diabetic mice (Yin et al, 2020). Emerging evidence indicates that many forms of PCD play vital roles in the cell death of SCs for treating diabetes and diabetes-related diseases, the identification of necroptosis and ferroptosis remains to be explored further.

Results

Conclusion