title: In vitro hepatic trans-differentiation of human mesenchymal stem cells using sera from congestive/ischemic liver during cardiac failure.
abstract: Cellular therapy for end-stage liver failures using human mesenchymal stem cells (hMSCs)-derived hepatocytes is a potential alternative to liver transplantation. Hepatic trans-differentiation of hMSCs is routinely accomplished by induction with commercially available recombinant growth factors, which is of limited clinical applications. In the present study, we have evaluated the potential of sera from cardiac-failure-associated congestive/ischemic liver patients for hepatic trans-differentiation of hMSCs. Results from such experiments were confirmed through morphological changes and expression of hepatocyte-specific markers at molecular and cellular level. Furthermore, the process of mesenchymal-to-epithelial transition during hepatic trans-differentiation of hMSCs was confirmed by elevated expression of E-Cadherin and down-regulation of Snail. The functionality of hMSCs-derived hepatocytes was validated by various liver function tests such as albumin synthesis, urea release, glycogen accumulation and presence of a drug inducible cytochrome P450 system. Based on these findings, we conclude that sera from congestive/ischemic liver during cardiac failure support a liver specific microenvironment for effective hepatic trans-differentiation of hMSCs in vitro.
authors.affiliation: Stem Cells and Molecular Biology Laboratory, Department of Biotechnology, Indian Institute of Technology Madras, Chennai, India; Stem Cells and Tissue Engineering Laboratory, International Centre for Cardiothoracic and Vascular Diseases, Frontier Lifeline, Chennai, India.
authors.forename: Dillip Kumar
authors.initials: DK
authors.lastname: Bishi
authors.affiliation: Stem Cells and Molecular Biology Laboratory, Department of Biotechnology, Indian Institute of Technology Madras, Chennai, India; Stem Cells and Tissue Engineering Laboratory, International Centre for Cardiothoracic and Vascular Diseases, Frontier Lifeline, Chennai, India.
authors.forename: Santosh
authors.initials: S
authors.lastname: Mathapati
authors.affiliation: Stem Cells and Tissue Engineering Laboratory, International Centre for Cardiothoracic and Vascular Diseases, Frontier Lifeline, Chennai, India.
authors.forename: Kotturathu Mammen
authors.initials: KM
authors.lastname: Cherian
authors.affiliation: Department of Engineering Design, Indian Institute of Technology Madras, Chennai, India.
authors.forename: Soma
authors.initials: S
authors.lastname: Guhathakurta
authors.affiliation: Stem Cells and Molecular Biology Laboratory, Department of Biotechnology, Indian Institute of Technology Madras, Chennai, India.
authors.forename: Rama Shanker
authors.initials: RS
authors.lastname: Verma
mesh_terms: D000328:Adult; D015703:Antigens, CD; D015415:Biomarkers / Q000378:metabolism; D015820:Cadherins / Q000235:genetics / Q000378:metabolism; D018929:Cell Culture Techniques; D048430:Cell Shape; D054338:Cell Transdifferentiation; D003470:Culture Media; D005260:Female; D015870:Gene Expression; D006333:Heart Failure / Q000097:blood; D056945:Hep G2 Cells; D022781:Hepatocytes / Q000378:metabolism; D006801:Humans; D007511:Ischemia / Q000097:blood; D008099:Liver / Q000098:blood supply; D008115:Liver Regeneration; D008297:Male; D059630:Mesenchymal Stem Cells / Q000502:physiology*; D008875:Middle Aged; D044967:Serum / Q000502:physiology; D000071250:Snail Family Transcription Factors; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism
chemical_list: D015703:Antigens, CD; D015415:Biomarkers; C513384:CDH1 protein, human; D015820:Cadherins; D003470:Culture Media; D000071250:Snail Family Transcription Factors; D014157:Transcription Factors