Persistent circulating human insulin in sheep transplanted in utero with human mesenchymal stem cells
Received 22 November 2009; received in revised form 7 February 2010; accepted 9 February 2010. published online 18 February 2010.
Objective
To determine if mesenchymal stem cells (MSC) derived from human fetal pancreatic tissue (pMSC) would engraft and differentiate in sheep pancreas following transplantation in utero.
Materials and Methods
A three-step culture system was established for generating human fetal pMSC. Sheep fetuses were transplanted during the fetal transplant receptivity period with human pMSC and evaluated for in situ and functional engraftment in their pancreas, liver, and bone marrow.
Results
Isolation and expansion of adherent cells from the human fetal pancreas yielded a cell population with morphologic and phenotypic characteristics similar to MSC derived from bone marrow. This putative stem cell population could undergo multilineage differentiation in vitro. Three to 27 months after fetal transplantation, the pancreatic engraftment frequency (chimeric index) was 79%, while functional engraftment was noted in 50% of transplanted sheep. Hepatic and marrow engraftment and expression was noted as well.
Conclusion
We have established a procedure for isolation of human fetal pMSC that display characteristics similar to bone marrow−derived MSC. In vivo results suggest the pMSC engraft, differentiate, and secrete human insulin from the sheep pancreas.
aDepartment of Animal Biotechnology, University of Nevada Reno, Reno, Nev., USA
bDivision of Rheumatology/Immunology, Department of Internal Medicine, University of Nevada School of Medicine/VA Sierra Health Care System, Reno, Nev., USA
Offprint requests to: John S. Pixley, M.D., Division of Rheumatology/Immunology, Department of Internal Medicine, University of Nevada School of Medicine, VA Sierra Health Care System, 1000 Locust Street, Reno, NV 89502-2597
ABSTRACT