Umbilical Cord‐Derived Mesenchymal Stem Cells Suppress Autophagy of T Cells in Patients with Systemic Lupus Erythematosus via Transfer of Mitochondria

Abstract

Aberrant autophagy played an important role in the pathogenesis of autoimmune diseases, especially in systemic lupus erythematosus (SLE). In this study, we showed that T cells from SLE patients had higher autophagic activity than that from healthy controls. A correlation between autophagic activity and apoptotic rate was observed in activated T cells. Moreover, activation of autophagy with rapamycin increased T cell apoptosis, whereas inhibition of autophagy with 3-MA decreased T cell apoptosis. Umbilical cord-derived mesenchymal stem cells (UC-MSCs) could inhibit respiratory mitochondrial biogenesis in activated T cells to downregulate autophagy and consequently decrease T cell apoptosis through mitochondrial transfer and thus may play an important role in SLE treatment.

Mitochondrial transfer from MSCs to T cells induces Treg differentiation and restricts inflammatory response

“…Hence, MitoT might represent an amenable system to study functional changes in T cells while enabling improved cell-based treatments, since MSCs are a main cell source for MitoT [12]. The scope of such immunometabolic and regulatory change has been in part addressed by Chen et al [13] who evidenced that UC-MSCs tended to correct the mitochondrial respiratory dysfunction and increased T-cell apoptosis of SLE patients, in concomitance with MitoT to PBMCs in vitro.…”

Stem cell-derived mitochondria transplantation: a novel strategy and the challenges for the treatment of tissue injury

“…Stem cells also donate their mitochondria to injured cells to resist oxidative stress and improve the state of cellular metabolism [ 49 ]. Thus, intercellular mitochondrial transfer holds a new approach to cure mitochondrial dysfunctional diseases using stem cells as a carrier [ 50 ].…”

Use of Human Umbilical Cord and Its Byproducts in Tissue Regeneration

“…Regenerative medicine is in continuous progress. Biochemical analysis, high throughput screening and bioinformatics contribute to advances in the area (Tomchuck et al, 2008;Arslan et al, 2013;Mitragotri et al, 2014;Akyurekli et al, 2015;Chen et al, 2016;Luz-Crawford et al, 2016;Caicedo et al, 2017;Chan et al, 2017;Ma et al, 2017;Amati et al, 2018;Court et al, 2018;de la Rosa et al, 2018;Li et al, 2018;Miliotis et al, 2019). Factors that stimulate the secretion of the biochemical cocktail, the ideal extraction techniques, active byproducts and possible combinations that lead to desired effects which respond to inflammatory signals by secreting cytokines and exosomes, need further study (Tomchuck et al, 2008;Arslan et al, 2013;Ma et al, 2017;Miliotis et al, 2019).…”

“…Factors that stimulate the secretion of the biochemical cocktail, the ideal extraction techniques, active byproducts and possible combinations that lead to desired effects which respond to inflammatory signals by secreting cytokines and exosomes, need further study (Tomchuck et al, 2008;Arslan et al, 2013;Ma et al, 2017;Miliotis et al, 2019). We hypothesize that the synthesis of these factors might have potential for tissue regeneration, immune regulation and healing (Akyurekli et al, 2015;Chen et al, 2016;Caicedo et al, 2017;Court et al, 2018;Luz-Crawford et al, 2019). Continuous research and clinical trials might provide more insight on the possibility of surgical applications, wound healing and tissue repair.…”