Adult human liver mesenchymal stem/progenitor cells participate to mouse liver regeneration after hepatectomy.
(2012) Cell Transplantation — Vol. x, n° x, p. x (2012)
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- The advances in stem cell science have promoted research on their use in liver regenerative medicine. Beyond the demonstration of their ability to display metabolic functions in vitro, candidate cells should demonstrate achievable in situ differentiation, and ability to participate to liver repopulation. In this work, we studied the in vivo behaviour of adult liver mesenchymal stem/progenitor cells (ADHLSCs) after transplantation into immuno-deficient mice. Kinetic of engraftment and in situ hepatogenic differentiation were analyzed. Response of transplanted ADHLSCs to regenerative stimulus has also been evaluated. Non-differentiated ADHLSCs were intrasplenically transplanted into SCID mice. Efficiency of transplantation was evaluated at the level of engraftment and in situ differentiation using immunohistochemistry, in situ hybridization and RT-PCR. After bromodeoxyuridine (BrdU) implantation, proliferation of transplanted ADHLSCs in response to 20% hepatectomy was assessed using immunohistochemistry. We demonstrated that ADHLSC engraftment in the SCID mouse liver was low, but remained stable up to 60 days post-transplantation, when albumin (ALB) immuno-positive ADHLSCs were still detected and organized as clusters. Co-expression of ornithine transcarbamylase (OTC) demonstrated ADHLSC in situ differentiation mostly near the hepatic portal vein. After 20% hepatectomy on one month transplanted mice, the percentage of BrdU and human ALB immuno-positive ADHLSCs increased from 3 to 28 days post-BrdU implantation to reach 31.3 ± 5.4% of the total analyzed human cells. In the current study, we demonstrate that transplanted ADHLSCs are able to differentiate in the non pre-conditioned SCID mouse liver mainly in the peri-portal area. In response to partial hepatectomy, integrated ADHLSCs proliferate and participate to recipient mouse liver regeneration.
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Khuu, D. N., Nyabi, O., Maerckx, C., Sokal, E., & Najimi, M. (2012). Adult human liver mesenchymal stem/progenitor cells participate to mouse liver regeneration after hepatectomy. Cell Transplantation, x(x), x. https://doi.org/10.3727/096368912X659853 (Original work published 2012)