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.