In�vitro differentiation of rhesus macaque bone marrow‑ and adipose tissue‑derived MSCs into hepatocyte‑like cells

Abstract

Orthotopic liver or hepatocyte transplantation is effective for the treatment of acute liver injury and end-stage chronic liver disease. However, both of these therapies are hampered by the extreme shortage of organ donors. The clinical application of cell therapy through the substitution of hepatocytes with mesenchymal stem cells (MSCs) that have been differentiated into hepatocyte-like cells (HLCs) for liver disease treatment is expected to overcome this shortage. Bone marrow and adipose tissue are two major sources of MSCs [bone marrow-derived MSCs (BM-MSCs) and adipose tissue-derived MSCs (AT-MSCs), respectively]. However, knowledge about the variability in the differentiation potential between BM-MSCs and AT-MSCs is lacking. In the present study, the hepatogenic differentiation potential of rhesus macaque BM-MSCs and AT-MSCs was compared with the evaluation of morphology, immunophenotyping profiles, differentiation potential, glycogen deposition, urea secretion and hepatocyte-specific gene expression. The results indicated that BM-MSCs and AT-MSCs shared similar characteristics in terms of primary morphology, surface markers and trilineage differentiation potential (adipogenesis, osteogenesis and chondrogenesis). Subsequently, the hepatogenic differentiation potential of BM-MSCs and AT-MSCs was evaluated by morphology, glycogen accumulation, urea synthesis and expression of hepatocyte marker genes. The results indicated that rhesus BM-MSCs and AT-MSCs had hepatogenic differentiation ability. To the best of our knowledge, this is the first report to detect the hepatogenic differentiation potential of rhesus macaque BM-MSCs and AT-MSCs. The present study provides the basis for the selection of seed cells that can trans-differentiate into HLCs for cytotherapy of acute or chronic liver injuries in either clinical or veterinary practice.

Mesenchymal Stem Cell–Derived Exosomes in Various Chronic Liver Diseases: Hype or Hope?

“…16,17 Despite being found in a variety of tissues, MSCs share comparable phenotypic characteristics, and some may even have extra features that are indicative of the source tissues. [17][18][19] MSCs can transform into a minimum of three different cell types, namely, adipocytes, chondrocytes, and osteocytes. 19,20 Because MSCs are able to distinguish, their use in clinical trials has expanded substantially.…”

“…[17][18][19] MSCs can transform into a minimum of three different cell types, namely, adipocytes, chondrocytes, and osteocytes. 19,20 Because MSCs are able to distinguish, their use in clinical trials has expanded substantially. 21 MSCs are now well recognized as a type of precursor cells that support the stroma and have the ability to differentiate into stroma-supporting cells.…”

“…In addition, they have immunomodulatory, apoptosis-inhibition, cell-regeneration, and anti-fibrotic properties. 13,19,[29][30][31][32][33] The liver, being a crucial organ in regulating immunity and metabolism, contains numerous immune cells, including myeloid and lymphoid cells. Disruption of hepatic immune homeostasis is often linked to various liver diseases.…”

Mechanisms of Action of Mesenchymal Stem Cells in Metabolic-Associated Fatty Liver Disease

“…HLCs are cells with similar functions and characteristics to normal hepatocytes. It has been proved in vitro and in vivo that MSCs could be induced to differentiate into HLCs and express hepatocyte specific markers, such as albumin (ALB) [7,8]. Recent studies have revealed that MSCs can alleviate hepatic injury, improve hepatic function, and promote liver tissue regeneration and repair.…”

Generation of metabolically functional hepatocyte‐like cells from dedifferentiated fat cells by Foxa2, Hnf4a and Sall1 transduction

“…A potential alternative to primary hepatocytes is hepatocyte‐like cells derived from mesenchymal stem cells, which are capable of differentiating into most mesodermal cell types, as well as endodermal cell types (Spees et al., 2016; Wang et al., 2020). Cultured mesenchymal stem cells are of advantage in that they can be obtained in high quantities without losing their multipotency, in comparison with nonproliferative hepatocytes.…”