Reversal of Hyperglycemia by Insulin-Secreting Rat Bone Marrow- and Blastocyst-Derived Hypoblast Stem Cell-Like Cells

Anujith Kumar, Antonio Lo Nigro, Conny Gysemans, Qing Cai, Camila Esguerra, Molly Nelson-Holte, Yves Heremans, María Jiménez-González, Angelo Porciuncula, Chantal Mathieu, Bert Binas, Harry Heimberg, Felipe Prosper, Bernhard Hering, Catherine M. Verfaillie, Miguel Barajas

Research output: Contribution to journalArticlepeer-review

10 Citations (Scopus)

Abstract

β-cell replacement may efficiently cure type 1 diabetic (T1D) patients whose insulin-secreting β-cells have been selectively destroyed by autoantigen-reactive T cells. To generate insulin-secreting cells we used two cell sources: rat multipotent adult progenitor cells (rMAPC) and the highly similar rat extra-embryonic endoderm precursor (rXEN-P) cells isolated under rMAPC conditions from blastocysts (rHypoSC). rMAPC/rHypoSC were sequentially committed to definitive endoderm, pancreatic endoderm, and β-cell like cells. On day 21, 20% of rMAPC/rHypoSC progeny expressed Pdx1 and C-peptide. rMAPCr/HypoSC progeny secreted C-peptide under the stimulus of insulin agonist carbachol, and was inhibited by the L-type voltage-dependent calcium channel blocker nifedipine. When rMAPC or rHypoSC differentiated d21 progeny were grafted under the kidney capsule of streptozotocin-induced diabetic nude mice, hyperglycemia reversed after 4 weeks in 6/10 rMAPC- and 5/10 rHypoSC-transplanted mice. Hyperglycemia recurred within 24 hours of graft removal and the histological analysis of the retrieved grafts revealed presence of Pdx1-, Nkx6.1- and C-peptide-positive cells. The ability of both rMAPC and HypoSC to differentiate to functional β-cell like cells may serve to gain insight into signals that govern β-cell differentiation and aid in developing culture systems to commit other (pluripotent) stem cells to clinically useful β-cells for cell therapy of T1D.

Original languageEnglish
Article numbere63491
JournalPLoS One
Volume8
Issue number5
DOIs
Publication statusPublished - 09-05-2013

All Science Journal Classification (ASJC) codes

  • Medicine(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Agricultural and Biological Sciences(all)

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