Therapeutic Potential of Adult Bone Marrow Stem Cells in Liver Disease and Delivery Approaches

Abstract

Hematopoietic stem cells (HSCs) and mesenchymal stem cell (MSCs) are two main subtypes of bone marrow stem cells. Extensive studies have been carried out to investigate the therapeutic potential of BMSCs in liver disease. A number of animal and human studies demonstrated that either HSCs or MSCs could be applied to therapeutic purposes in certain liver diseases. The diseased liver may recruit migratory stem cells, particularly from the bone marrow, to generate hepatocyte-like cells either by transdifferentiation or cell fusion. Transplantation of BMSCs has therapeutic effects of restoration of liver mass and function, alleviation of fibrosis and correction of inherited liver diseases. There are still controversial results over the potential effects of BMSCs on liver diseases, and some of the discrepancies are thought to be lied in the differences of experimental protocols, differences in individual research laboratory, and the uncertainties of the techniques employed. Several potential approaches for BMSCs delivery in liver diseases have been proposed in animal studies and human trials. BMSCs can be delivered via intraportal vein, systemic infusion, intraperitoneal, intrahepatic, intrasplenic. The optimal stem cells delivery should be easy to perform, less invasive and traumatic, minimum side effects, and with high cells survival rate. In this review, we focus on the up-to-date evidence of therapeutic effects of BMSCs on liver disease, the characteristics of various delivery approaches, and the considerations for future studies.

Bone marrow-derived mesenchymal stem cells attenuate acute liver injury and regulate the expression of fibrinogen-like-protein 1 and signal transducer and activator of transcription 3

“…The mechanisms by which BMSCs alleviate acute liver injury involve challenges. It has primarily been reported that BMSCs are able to differentiate into hepatocyte-like cells and thereby promote liver tissue recovery and healing (15). However, there is increasing awareness of the contribution of BMSC-induced generation of trophic molecules by paracrine action in the alleviation of acute liver injury.…”

Prognostic potential of precise molecular diagnosis of Autosomal Recessive Osteopetrosis with respect to the outcome of bone marrow transplantation

“…The potentialities of this kind of approach are currently under consideration in several fields, as demonstrated by the growing list of publications on this topic (Corsten and Shah 2008;Granero-Molto et al 2008;Liu et al 2008;Meyerrose et al 2008;Xu and Liu 2008;and others). The rationale in the application of MSCT to RANKL-dependent ARO is that in this way the patient would receive the specific precursor cells able to differentiate into normal osteoblasts, producing in situ the cytokine RANKL, which is defective in the recipient, and thus allowing the differentiation of osteoclast precursors into normal, functional cells.…”

Bone Marrow–Derived Stromal Cell Therapy in Cirrhosis: Clinical Evidence, Cellular Mechanisms, and Implications for the Treatment of Hepatocellular Carcinoma

“…Demonstrations of the capacity of MSCs, HSCs, and EPCs to ameliorate liver injury have raised considerable interest in the use of autologous BMSC transplantation as a potential therapy for liver cirrhosis [58,90,92,97,156,157]. A number of clinical trials have investigated autologous BMSC transfusion in patients with chronic liver disease (Table 3).…”