Persistent circulating human insulin in sheep transplanted in utero with human mesenchymal stem cells.
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.


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.


CONCLUSIONS
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.
Ersek
Adel
A
Department of Animal Biotechnology, University of Nevada Reno, Reno, NV, USA.
Pixley
John S
JS
Goodrich
A Daisy
AD
Porada
Christopher D
CD
Almeida-Porada
Graca
G
Thain
David S
DS
Zanjani
Esmail D
ED
D000818:Animals; D002454:Cell Differentiation; D002478:Cells, Cultured; D005260:Female; D005434:Flow Cytometry; D006801:Humans; D007150:Immunohistochemistry; D007328:Insulin / Q000097:blood* / Q000378:metabolism; D007515:Islets of Langerhans / Q000378:metabolism*; D045164:Mesenchymal Stem Cell Transplantation; D059630:Mesenchymal Stem Cells / Q000166:cytology*; D011247:Pregnancy; D012015:Reference Standards; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012756:Sheep
D007328:Insulin