The role of MSCs and CAR-MSCs in cellular immunotherapy

Abstract

Chimeric antigen receptors (CARs) are widely used by T cells (CAR-T cells), natural killer cells dendritic cells and macrophages, and they are of great importance in cellular immunotherapy. However, the use of CAR-related products faces several challenges, including the poor persistence of cells carrying CARs, cell dysfunction or exhaustion, relapse of disease, immune effector cell-associated neurotoxicity syndrome, cytokine release syndrome, low efficacy against solid tumors and immunosuppression by the tumor microenvironment. Another important cell therapy regimen involves mesenchymal stem cells (MSCs). Recent studies have shown that MSCs can improve the anticancer functions of CAR-related products. CAR-MSCs can overcome the flaws of cellular immunotherapy. Thus, MSCs can be used as a biological vehicle for CARs. In this review, we first discuss the characteristics and immunomodulatory functions of MSCs. Then, the role of MSCs as a source of exosomes, including the characteristics of MSC-derived exosomes and their immunomodulatory functions, is discussed. The role of MSCs in CAR-related products, CAR-related product-derived exosomes and the effect of MSCs on CAR-related products are reviewed. Finally, the use of MSCs as CAR vehicles is discussed. Graphical Abstract

Human umbilical cord-derived mesenchymal stem cells and auto-crosslinked hyaluronic acid gel complex for treatment of intrauterine adhesion

“…Migration of MSCs to targeted tissues is an essential process encompassing their viability and guided movement [ 37 ]. The ability of MSCs to migrate to ischemic or damaged tissues is a significant characteristic [ 38 ].…”

Simulated microgravity increases CD226+Lin−CD117−Sca1+ mesenchymal stem cells in mice

“…The mechanisms by which MSCs participate in tissue repair are under intense study. On one hand, MSCs can differentiate into chondrocytes, osteoblasts, myocytes, and adipocytes (Yan et al., 2023 ). On the other hand, MSCs have immunomodulatory ability mediated by cell‐to‐cell interactions, secreted cytokines, growth factors, and exosomes (Wang et al., 2014 ).…”

“…MSCs can secrete a variety of cytokines, such as IL‐6, M‐CSF and RANKL, which lead to osteoclastogenesis (Phetfong et al., 2016 ; Sharaf‐Eldin et al., 2016 ; Yan et al., 2023 ). Our data showed CD226 + MSCs expressed higher levels of IL‐6, M‐CSF, and RANKL compared to CD226 − MSCs.…”

“…MSCs have strong self‐renewal ability and multidirectional differentiation potential. In addition, MSCs have the characteristics of immune regulation, hematopoietic support, tissue repair, and regeneration (Ding et al., 2023 ; Lin et al., 2023 ; Yan et al., 2023 ). It has been reported that the proliferation and osteogenesis of MSCs could be inhibited by simulated microgravity (Baran et al., 2022 ; Dai et al., 2007 ; Yan et al., 2015 ).…”

Mesenchymal-Stem-Cell-Based Therapy against Gliomas

“…Therefore, to improve the effectiveness of MSC-based therapy against cancer, methods must be sought to overcome these limitations [90]. The use of CAR-T cells [91][92][93] or conjugation with nanoparticles [94][95][96][97][98] are two potential ways to improve the tropism of MSCs.…”