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

Adel Ersek, John S Pixley, A Daisy Goodrich, Christopher D Porada, Graca Almeida-Porada, David S Thain, Esmail D Zanjani

Research output: Contribution to journalArticlepeer-review

16 Citations (Scopus)

Abstract

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.

Original languageEnglish
Pages (from-to)311-320
Number of pages10
JournalExperimental Hematology
Volume38
Issue number4
DOIs
Publication statusPublished - Apr 2010
Externally publishedYes

Keywords

  • Animals
  • Cell Differentiation
  • Cells, Cultured
  • Female
  • Flow Cytometry
  • Humans
  • Immunohistochemistry
  • Insulin/blood
  • Islets of Langerhans/metabolism
  • Mesenchymal Stem Cell Transplantation
  • Mesenchymal Stem Cells/cytology
  • Pregnancy
  • Reference Standards
  • Reverse Transcriptase Polymerase Chain Reaction
  • Sheep

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