Stem Cell Therapy for Liver Disease: Parameters Governing the Success of Using Bone Marrow Mesenchymal Stem Cells

Abstract

Background & Aims-Liver transplantation is the primary treatment for various end-stage hepatic diseases but is hindered by the lack of donor organs and by complications associated with rejection and immunosuppression. There is increasing evidence to suggest the bone marrow is a transplantable source of hepatic progenitors. We previously reported that multipotent bone marrow-derived mesenchymal stem cells differentiate into functional hepatocyte-like cells with almost 100% induction frequency under defined conditions, suggesting the potential for clinical applications. The aim of this study was to critically analyze the various parameters governing the success of bone marrow-derived mesenchymal stem cell-based therapy for treatment of liver diseases.

Efficient human fetal liver cell isolation protocol based on vascular perfusion for liver cell-based therapy and case report on cell transplantation

“…This is interesting because, in addition to hepatic cells, bone marrow-derived hematopoietic and mesenchymal cells have already been examined in studies of the development of clinical CT protocols for liver regeneration. 27,28 The expression of hepatic markers in the characterized cell preparation overlapped with the expression of markers of adult human hepatic progenitor cells to some degree, as previously reported by other groups. 33,[40][41][42] Because of their availability, most studies of the isolation and in vitro propagation of adult liver progenitors have been performed with animal-derived cells, 40 and the majority of the isolation strategies for liver progenitors are based on the in vivo activation of the progenitor cell population 43 followed by the enzymatic digestion of tissue fragments and the selection of progenitors with a variety of techniques, such as centrifugation techniques, fluorescence-activated cell sorting, 46 and selective cell aggregate formation.…”

“…Although human FL tissue obtained during the first trimester mainly exhibits cells expressing hematopoietic [21][22][23][24] and endothelial cell markers, 25 the majority of the cells expressing hepatic markers appear in the early second trimester. 26 The presence of hematopoietic cells could be interesting because initial clinical studies of the transplantation of bone marrow-derived stem cell marker-positive cells 27 and bone marrow-derived mesenchymal stem cell (MSC) marker-expressing cells 28 have indicated that both hematopoietic and mesenchymal cell populations in the human FL may also be of interest for the development of liver CT therapy.…”

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

“…The efficiency of MSC treatment in FHF patients was evidenced by the fact that FHF was rescued 4 weeks after MSC transplantation. 24 The rapid therapeutic effect indicates that the paracrine secretions of MSCs play a more important role than differentiation in MSC-mediated restoration of liver function. 25 IMDs including Crigler-Najjar syndrome 26 and primary systemic amyloidosis 27 have been successfully treated by stem cell transplantation in clinical trials.…”

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

“…5 Recent work suggests that transplantation of native MSCs can alleviate liver injury through paracrine effects. 6 MSC-derived exosomes (MSC-Ex), membrane-enclosed vesicles found in MSC-conditioned medium (MSC-CM), have been reported to contribute to angiogenesis, neurite outgrowth, and skeletal muscle regeneration. [7][8][9] We previously demonstrated that hucMSCs and hucMSC-Ex could alleviate liver fibrosis, promote liver and renal injury repair, and improve wound healing.…”

“…[15][16][17][18][19] Antioxidant therapy has been considered for treatment of liver diseases, and previous work suggests that transplanted MSCs can restore liver function. 6,20 However, how MSC-Ex modulate oxidative stress in liver injury repair is unclear. Glutathione peroxidase 1 (GPX1), a critical human antioxidant, 21 detoxifies hydrogen peroxide and upregulates GPX1 activity to promote cell survival, but whether hucMSC-Exmediated delivery of GPX1 can restore liver function is unknown.…”