Advances in Mesenchymal Stem Cell Therapy for Immune and Inflammatory Diseases: Use of Cell-Free Products and Human pluripotent Stem Cell-Derived Mesenchymal Stem Cells

Abstract

Mesenchymal stem cell therapy (MSCT) for immune and inflammatory diseases continues to be popular based on progressive accumulation of preclinical mechanistic evidence. This has led to further expansion in clinical indications from graft rejection, autoimmune diseases, and osteoarthritis, to inflammatory liver and pulmonary diseases including COVID-19. A clear trend is the shift from using autologous to allogeneic MSCs, which can be immediately available as off-the-shelf products. In addition, new products such as cell-free exosomes and human pluripotent stem cell (hPSC)-derived MSCs are exciting developments to further prevalent use. Increasing numbers of trials have now published results in which safety of MSCT has been largely demonstrated. While reports of therapeutic endpoints are still emerging, efficacy can be seen for specific indications-including graft-vs-host-disease, strongly Th17-mediated autoimmune diseases, and osteoarthritiswhich are more robustly supported by mechanistic preclinical evidence. In this review, we update and discuss outcomes in current MSCT clinical trials for immune and inflammatory disease, as well as new innovation and emerging trends in the field.

Allogeneic vs. autologous mesenchymal stem/stromal cells in their medication practice

“…Acknowledging a connection between the biological properties of MSCs and MSC-associated microenvironmental factors is conducive for better understanding of MSCs’ contribution to their medical practice, promisingly or uncertainly. As of March 2021, there are almost 1000 clinical trials registered on the clinicaltrials.gov ( www.clinicaltrials.gov ) [ 159 ] using autologous and allogeneic MSCs for treatment of the variety of categories of human diseases and medical conditions. Clinical data available show that the therapeutic benefits of using either autologous or allogeneic MSCs as a better option are inconclusive.…”

The Latest Developments in Immunomodulation of Mesenchymal Stem Cells in the Treatment of Intrauterine Adhesions, Both Allogeneic and Autologous

“…On the other hand, an obvious solution is to immediately use autologous MSCs as a ready-made product. In addition, new products such as acellular exosomes and MSCs derived from human pluripotent stem cells (hPSCs) are exciting developments that are attracting significant attention ( 136 ).…”

Therapeutic Implications of Mesenchymal Stromal Cells and Their Extracellular Vesicles in Autoimmune Diseases: From Biology to Clinical Applications

“…Because of their potential to differentiate into several tissues, their extensive in vitro expansion, and their broad immunoregulatory properties, involving cells associated with both innate and adaptive immunity, MSCs have drawn much attention in the field of tissue repair [2][3][4]. In support of this, several preclinical and clinical studies evaluating the immunomodulatory role of MSCs have indeed demonstrated promising results in terms of attenuating inflammatory and autoimmune disorders [1].…”

“…Knowledge regarding the etiology, pathophysiology, and clinical manifestations of autoimmune disorders has witnessed considerable progress during the last years and this has paved the way for the development of sophisticated treatments targeting molecular pathways and immune deregulations implicated in disease pathogenesis. One such novel therapeutic modality involves the use of mesenchymal stromal sells (MSCs) [ 1 ].…”