Mesenchymal Stromal Cells in Solid Organ Transplantation

Abstract

Over the past decade, the clinical application of mesenchymal stromal cells (MSCs) has generated growing enthusiasm as an innovative cell-based approach in solid organ transplantation (SOT). These expectations arise from a significant number of both transplant- and non–transplant-related experimental studies investigating the complex anti-inflammatory, immunomodulatory, and tissue-repair properties of MSCs. Promising preclinical results have prompted clinical trials using MSC-based therapy in SOT. In the present review, the general properties of MSCs are summarized, with a particular emphasis on MSC-mediated impact on the immune system and in the ischemic conditioning strategy. Next, we chronologically detail all clinical trials using MSCs in the field of SOT. Finally, we envision the challenges and perspectives of MSC-based cell therapy in SOT.

Heme Oxygenase-1-Modified Bone Marrow Mesenchymal Stem Cells Combined with Normothermic Machine Perfusion Repairs Bile Duct Injury in a Rat Model of DCD Liver Transplantation via Activation of Peribiliary Glands through the Wnt Pathway

“…BMMSCs have functions of immunomodulation and tissue repair, prompting widespread interest in their use in the field of organ transplantation [ 17 , 18 ]. However, BMMSC application still faces two unresolved and unavoidable problems.…”

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

“…53,54 MSC modulation of CD4 T cells from effector to regulatory phenotypes was also seen in an early report of solid organ transplant using a murine heart semi-allograft model, 55 with rapid accumulation of other studies on MSCs prolonging survival and/or preventing rejection of other organ/tissue types including skin, 56 pancreatic islet cells, 57 liver, 58 kidney, 59 and cornea. [60][61][62] A common finding in these studies is the ability of MSCs to promote IL-10-producing immune cells, surprisingly in both adaptive as well as innate leukocytes. 55,57 These early clinical and preclinical successes have made graft rejection a leading indication for use of MSCT.…”

Applications of CRISPR technologies in transplantation

“…34,35 Another potential target for cellbased therapy is a mesenchymal stem/stromal cell (MSC) due to its anti-inflammatory, immunomodulatory, and tissue-repair properties that can play critical roles during solid organ transplantation. 36,37 CRISPR manipulation of those cells will demonstrate potential therapeutic approaches in the near future. 38…”

“…In a mouse model of this disease, both in vivo and ex vivo CRISPR‐mediated gene editing in hepatocytes improved liver metabolism and demonstrated the potential of the CRISPR system as an alternative therapy for cell/organ transplantation 34,35 . Another potential target for cell‐based therapy is a mesenchymal stem/stromal cell (MSC) due to its anti‐inflammatory, immunomodulatory, and tissue‐repair properties that can play critical roles during solid organ transplantation 36,37 . CRISPR manipulation of those cells will demonstrate potential therapeutic approaches in the near future 38 …”