Mesenchymal stem cell–derived molecules directly modulate hepatocellular death and regeneration in vitro and in vivo

Abstract

These data provide the first clear evidence that MSC-CM therapy provides trophic support to the injured liver by inhibiting hepatocellular death and stimulating regeneration, potentially creating new avenues for the treatment of FHF.

The role of microvesicles in tissue repair

“…Recent findings indicate that liver regeneration triggered by stem cells depends on the release of paracrine factors. 52,53 We recently showed that MVs released by adult stem cells residing in the liver (HLSCs) may, in turn, transfer genetic information from stem cells to target cells that may regulate altered functions and repair damaged tissues without directly replacing parenchymal cells. 54 HLSCs are a stem cell population resident in the human adult liver with a mesenchymal phenotype and a partial commitment in hepatocytes that makes them able to induce liver regeneration when injected in acetaminophen-treated mice.…”

hucMSC Exosome-Derived GPX1 Is Required for the Recovery of Hepatic Oxidant Injury

“…[31][32][33] This therapeutic effect may include transdifferentiation of MSCs into hepatocytelike cells, secretion of anti-inflammatory factors, and hepatocyte regeneration promotion at the site of injury. [34][35][36] Interestingly, Bruno's group confirmed that microvesicles derived from MSCs could protect against acute renal tubular injury via cell-tocell communication.…”

Implications of the immunoregulatory functions of mesenchymal stem cells in the treatment of human liver diseases

“…[4][5][6] However, in a culture of human bone marrowderived MSCs (BM-MSCs) and hepatocytes, BM-MSCs that undergo hepatic differentiation probably account for only a small percentage of the population, 7 and any differentiation may not significantly change the outcome of the bone marrow stromal cell (BMSC) and hepatocyte coculture experiments. 8 MSCs have recently emerged as promising candidates for cell-based immunotherapy because these cells can modulate the immune responses in various ways. MSCs can produce a series of growth factors, cytokines and signal molecules that can potentially suppress inflammatory responses, reduce hepatocyte apoptosis, regress liver fibrosis, enhance hepatocyte functionality and stimulate the proliferation of endogenous hepatocytes 9 ( Figure 1).…”

“…In rat models of acute liver injury, human BMSCs or MSC-conditioned medium transplantation significantly reduced rat mortality; this was found to be correlated with a decrease in the number of apoptotic hepatocytes. 8,12 Furthermore, MSCs can also secrete several cytokines such as HGF, epidermal growth factor, IL-6 and TNF-a to stimulate hepatocyte proliferation and maintain hepatocyte function, as indicated by the high levels of albumin and urea secretion. 13 These secreted components of MSCs can enhance liver regeneration in a fulminant hepatic failure (FHF) model.…”