NOVEL MANAGEMENT OF ACUTE OR SECOUNDARY BILIARY LIVER CONDITIONS USING HEPATICALLY-DIFFERENTIATED HUMAN DENTAL-PULP CELLS.

Tissue engineering. Part A

PubMedID: 25234861

Ishkitiev N, Yaegaki K, Imai T, Tanaka T, Fushimi N, Mitev V, Okada M, Tominaga N, Ono S, Ishikawa H. NOVEL MANAGEMENT OF ACUTE OR SECOUNDARY BILIARY LIVER CONDITIONS USING HEPATICALLY-DIFFERENTIATED HUMAN DENTAL-PULP CELLS. Tissue Eng Part A. 2014;.
The current definitive treatment for acute or chronic liver condition, i.e. cirrhosis, is liver transplantation from a limited number of donors who might cause complications after donation. Hence bone marrow stem cell transplantation is developed, but tumorigenicity is remains. We have recently developed a protocol for hepatic differentiation of CD117+ stem cells from human exfoliated deciduous teeth (SHED). In the present study we examine whether hepatically in vitro differentiated (hd) SHED could treat acute liver injury and secondary biliary cirrhosis. The CD117+ cell fraction was magnetically separated form SHED and then differentiated into hepatocyte-like cells in vitro. The cells were transplanted into rats with either ALI or induced secondary biliary cirrhosis. Engraftment of human liver cells was determined immunohistochemically and by in situ hybridization. Recovery of liver function was examined by means of histochemical and serological tests. Livers of transplanted animals were strongly positive for human immunohistochemical factors, and in situ hybridization confirmed engraftment of human hepatocytes. The tests for recovery of liver function confirmed the presence of human hepatic markers in the animals' blood serum, reduction of fibrosis and functional integration of transplanted human cells into livers. The risk of malignancy was not found. We show that in vitro hdSHED engraft morphologically and functionally into the livers of rats having acute injury or secondary biliary cirrhosis. SHED are readily-accessible adult stem cells, capable of proliferating in large numbers before differentiating in vitro. This makes SHED an appropriate and safe stem-cell source for regenerative medicine.