Current status of clinical trials assessing mesenchymal stem cell therapy for graft versus host disease: a systematic review

Abstract

Background Graft-versus-host disease (GVHD) is a common fatal complication of hematopoietic stem cell transplantation (HSCT), where steroids are used as a treatment option. However, there are currently no second-line treatments for patients that develop steroid-resistance (SR). Mesenchymal stem cells (MSCs) have immunomodulatory functions and can exert immunosuppressive effects on the inflammatory microenvironment. A large number of in vitro experiments have confirmed that MSCs can significantly inhibit the proliferation or activation of innate and adaptive immune cells. In a mouse model of GVHD, MSCs improved weight loss and increased survival rate. Therefore, there is great promise for the clinical translation of MSCs for the prevention or treatment of GVHD, and several clinical trials have already been conducted to date. Main body In this study, we searched multiple databases and found 79 clinical trials involving the use of MSCs to prevent or treat GVHD and summarized the characteristics of these clinical trials, including study design, phase, status, and locations. We analyzed the results of these clinical trials, including the response and survival rates, to enable researchers to obtain a comprehensive understanding of the field’s progress, challenges, limitations, and future development trends. Additionally, factors that might result in inconsistencies in clinical trial results were discussed. Conclusion In this study, we attempted to analyze the clinical trials for MSCs in GVHD, identify the most suitable group of patients for MSC therapy, and provide a new perspective for the design of such trials in the future.

Chitosan Tubes Inoculated with Dental Pulp Stem Cells and Stem Cell Factor Enhance Facial Nerve-Vascularized Regeneration in Rabbits

“…Accordingly, the more models in vivo are essential and very important to be able to translate the achievements to human medicine from one health perspective. 66 , 67 …”

How mesenchymal stem cell cotransplantation with hematopoietic stem cells can improve engraftment in animal models

“…A recent study found that the cell source chosen is influenced by a variety of patient- and diagnosis-related characteristics, as well as the availability of appropriately matched donors, leaving the question of which cell source is superior or has more benefits unanswered[ 39 ]. The recent systematic review of clinical trials[ 40 ] also reported the use of the BM HSCs as the main source by IV transplantation. Wu et al [ 20 ] reported transplantation of a pool of human nucleated cells, Huang et al [ 10 ] and Lim et al [ 21 ] reported the use of a mononuclear cell pool without any cell selection process, and Fernández-García et al [ 17 ] used LSK cells.…”

“…Notwithstanding these methodological limitations in the preclinical research, clinical trials have reported significant results related to the increase in engraftment and survival rate through HSC and MSC cotransplantation. The recent systematic reviews of clinical trials[ 4 , 40 , 58 ] have shown that the more homogeneous the MSCs are in terms of the donor, source, extraction method, culture, and other aspects, the better is their efficacy and potentially, the less treatment dose required, and therefore the less likely they are cause adverse events. These clinical trial reviews showed that use of allogeneic MSC cotransplantation in allo-HSC, in phase II, or autogenic sources of MSC in phases I and II during cotransplantation of HSC and MSC increased the survival rate in clinical trials compared with other animal studies.…”

“…Such understanding will help in the creation of much-needed clinically applicable potency assays, as well as tactics to boost MSC potency, such as genetically editing[ 5 ] MSCs, and aims to improve manufacturing protocols; all of which are key components of long-term success. The second hurdle is that investigators must comprehend better the timing of MSC activity in phase II and III clinical trials[ 4 , 40 ].…”

Therapeutic Strategy of Mesenchymal-Stem-Cell-Derived Extracellular Vesicles as Regenerative Medicine

“…More than 500 clinical research on MSC is underway in the world for various target diseases, including rheumatoid arthritis, systemic lupus erythematosus, Crohn’s disease, myocardial infarction, Parkinson’s disease, spinal cord injury, osteoarthritis, and graft-versus-host disease (GVHD) [ 257 , 258 , 259 , 260 , 261 , 262 , 263 , 264 , 265 , 266 ]. MSCs other than those derived from bone marrow are also being clinically applied.…”