Generation of functional hepatocyte-like cells from human deciduous periodontal ligament stem cells

Abstract

Human deciduous periodontal ligament stem cells have been introduced for as an easily accessible source of stem cells from dental origin. Although recent studies have revealed the ability of these stem cells in multipotential attribute, their efficiency of hepatic lineage differentiation has not been addressed so far. The aim of this study is to investigate hepatic lineage fate competence of periodontal ligament stem cells through direct media induction. Differentiation of periodontal ligament stem cells into hepatocyte-like cells was conducted by the exposure of two phase media induction. First phase was performed in the presence of hepatocyte growth factors to induce a definitive endoderm formation. In the subsequent phase, the cells were treated with oncostatin M and dexamethosone followed by insulin and transferrin to generate hepatocyte-like cells. Hepatic-related characters of the generated hepatocyte-like cells were determined at both mRNA and protein level followed by functional assays. Foremost changes observed in the generation of hepatocyte-like cells were the morphological features in which these cells were transformed from fibroblastic shape to polygonal shape. Temporal expression of hepatic markers ranging from early endodermal up to late markers were detected in the hepatocyte-like cells. Crucial hepatic markers such as glycogen storage, albumin, and urea secretion were also shown. These findings exhibited the ability of periodontal ligament stem cells of dental origin to be directed into hepatic lineage fate. These cells can be regarded as an alternative autologous source in the usage of stem cell-based treatment for liver diseases.

Present Status of Research on the Regenerative Potential of Dental Pulp Stem Cells in Malaysia: A Systematic Review

“…Interestingly, studies conducted on the interest and attitude towards the use of stem cells in regenerative therapy received a highly positive response from the dentists in South Africa (73%) and nursing students in USM (76.1%) 26,27 . As, several in vitro and in vivo studies have shown the regenerative potential of SHED/DPSCs (to cure or improve the condition of diseases, such as type 1 diabetes, neurological diseases, immunodeficiency diseases, and diseases of bone and cartilages) 10,[13][14][15][16]28 , researchers should take the initiatives to explore the potential of SHED/DPSCs. Dentists or physicians are needed to explain the potential of SHED/DPSCs to the patients to make them aware of their presence.…”

“…DPSCs have drawn considerable attention just after their discovery by Gronthos et al in the year 2000 12 , and several researches have been reported their potential to differentiate into different types of cell lineages such as cardiomyocytes, beta cells, hepatocytes, neuronal cells etc. 10,[13][14][15][16] . Their MSCs like characteristics and immunomodulatory properties have also been acknowledged by several researchers 11,17 .…”

Mass acquisition of human periodontal ligament stem cells

“…PDLSCs have similar features to BMMSCs and exhibit self-renewal capacity and multipotency[ 39 ]. These cells have the potential to undergo triploblastic differentiation with the ability to differentiate into not only osteoblasts, adipocytes, chondrocytes, cementoblasts, and tendon/ligament fibroblasts[ 40 , 41 ] but also myocytes[ 42 ], neural cells[ 43 ], retinal cells[ 44 ], endothelial cells[ 45 ], pancreatic islet cells[ 46 ], and hepatic cells[ 47 ]. In addition, PDLSCs express cell surface markers such as STRO-1, CD146/MUC18[ 36 ], CD44, and CD90 (markers associated with stromal cells), CD105 and CD166 (markers associated with stromal cells and endothelial cells)[ 48 ], and CD10, CD26, CD29, CD73, and CD349/FZD9[ 49 ] but do not express hematopoietic cell surface markers such as CD31 and CD45, similar to BMMSCs[ 50 ].…”