title: Novel management of acute or secondary biliary liver conditions using hepatically differentiated human dental pulp cells.
abstract: The current definitive treatment for acute or chronic liver condition, that is, cirrhosis, is liver transplantation from a limited number of donors, which might cause complications after donation. Hence, bone marrow stem cell transplantation has been developed, but the risk of carcinogenesis 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 SHED hepatically differentiated (hd) in vitro could be used to treat acute liver injury (ALI) and secondary biliary cirrhosis. The CD117(+) cell fraction was magnetically separated from 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 and lack of fibrosis and functional integration of transplanted human cells into livers. No evidence of malignancy was 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.
authors.affiliation: 1 Department of Oral Health, School of Life Dentistry at Tokyo, Nippon Dental University , Tokyo, Japan .
authors.forename: Nikolay
authors.initials: N
authors.lastname: Ishkitiev
authors.forename: Ken
authors.initials: K
authors.lastname: Yaegaki
authors.forename: Toshio
authors.initials: T
authors.lastname: Imai
authors.forename: Tomoko
authors.initials: T
authors.lastname: Tanaka
authors.forename: Naho
authors.initials: N
authors.lastname: Fushimi
authors.forename: Vanyo
authors.initials: V
authors.lastname: Mitev
authors.forename: Mio
authors.initials: M
authors.lastname: Okada
authors.forename: Noriko
authors.initials: N
authors.lastname: Tominaga
authors.forename: Sachie
authors.initials: S
authors.lastname: Ono
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Ishikawa
mesh_terms: D000208:Acute Disease; D053687:Adult Stem Cells / Q000166:cytology / Q000637:transplantation*; D000818:Animals; D061249:Batch Cell Culture Techniques / Q000379:methods; D002454:Cell Differentiation; D002478:Cells, Cultured; D003782:Dental Pulp / Q000166:cytology*; D022781:Hepatocytes / Q000166:cytology* / Q000637:transplantation*; D006801:Humans; D008103:Liver Cirrhosis / Q000473:pathology / Q000628:therapy*; D008297:Male; D011923:Rats, Nude; D023822:Tissue Engineering / Q000379:methods; D014080:Tooth Exfoliation; D016896:Treatment Outcome