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Mobilization of hepatic mesenchymal stem cells from human liver grafts
Author(s) -
Pan Qiuwei,
Fouraschen Suomi M. G.,
Kaya Fatima S. F. Aerts,
Verstegen Monique M.,
Pescatori Mario,
Stubbs Andrew P.,
van IJcken Wilfred,
van der Sloot Antoine,
Smits Ron,
Kwekkeboom Jaap,
Metselaar Herold J.,
Kazemier Geert,
de Jonge Jeroen,
Tilanus Hugo W.,
Wagemaker Gerard,
Janssen Harry L. A.,
van der Laan Luc J. W.
Publication year - 2011
Publication title -
liver transplantation
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.814
H-Index - 150
eISSN - 1527-6473
pISSN - 1527-6465
DOI - 10.1002/lt.22260
Subject(s) - mesenchymal stem cell , stem cell , stem cell transplantation for articular cartilage repair , transplantation , medicine , immunology , regenerative medicine , clinical uses of mesenchymal stem cells , microchimerism , cancer research , bone marrow , microbiology and biotechnology , biology , cellular differentiation , adult stem cell , pathology , fetus , gene , pregnancy , biochemistry , genetics
Extensive studies have demonstrated the potential applications of bone marrow–derived mesenchymal stem cells (BM‐MSCs) as regenerative or immunosuppressive treatments in the setting of organ transplantation. The aims of the present study were to explore the presence and mobilization of mesenchymal stem cells (MSCs) in adult human liver grafts and to compare their functional capacities to those of BM‐MSCs. The culturing of liver graft preservation fluids (perfusates) or end‐stage liver disease tissues resulted in the expansion of MSCs. Liver‐derived mesenchymal stem cells (L‐MSCs) were equivalent to BM‐MSCs in adipogenic and osteogenic differentiation and in wingless‐type‐stimulated proliferative responses. Moreover, the genome‐wide gene expression was very similar, with a 2‐fold or greater difference found in only 82 of the 32,321 genes (0.25%). L‐MSC differentiation into a hepatocyte lineage was demonstrated in immunodeficient mice and in vitro by the ability to support a hepatitis C virus infection. Furthermore, a subset of engrafted MSCs survived over the long term in vivo and maintained stem cell characteristics. Like BM‐MSCs, L‐MSCs were found to be immunosuppressive; this was shown by significant inhibition of T cell proliferation. In conclusion, the adult human liver contains an MSC population with a regenerative and immunoregulatory capacity that can potentially contribute to tissue repair and immunomodulation after liver transplantation. Liver Transpl 17:596‐609, 2011. © 2011 AASLD.