Reversal of hyperglycemia by insulin-secreting rat bone marrow- and blastocyst-derived hypoblast stem cell-like cells.
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...
| Main Authors: | , , , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Public Library of Science (PLoS)
2013-01-01
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| Series: | PLoS ONE |
| Online Access: | http://europepmc.org/articles/PMC3650069?pdf=render |
| _version_ | 1819019508062355456 |
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| author | 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 |
| author_facet | 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 |
| author_sort | Anujith Kumar |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-12-21T03:36:25Z |
| format | Article |
| id | doaj.art-d86dfe388de6450e8fdcfad800dc1683 |
| institution | Directory Open Access Journal |
| issn | 1932-6203 |
| language | English |
| last_indexed | 2024-12-21T03:36:25Z |
| publishDate | 2013-01-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS ONE |
| spelling | doaj.art-d86dfe388de6450e8fdcfad800dc16832022-12-21T19:17:19ZengPublic Library of Science (PLoS)PLoS ONE1932-62032013-01-0185e6349110.1371/journal.pone.0063491Reversal of hyperglycemia by insulin-secreting rat bone marrow- and blastocyst-derived hypoblast stem cell-like cells.Anujith KumarAntonio Lo NigroConny GysemansQing CaiCamila EsguerraMolly Nelson-HolteYves HeremansMaría Jiménez-GonzálezAngelo PorciunculaChantal MathieuBert BinasHarry HeimbergFelipe ProsperBernhard HeringCatherine M VerfaillieMiguel Barajasβ-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.http://europepmc.org/articles/PMC3650069?pdf=render |
| spellingShingle | 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 Reversal of hyperglycemia by insulin-secreting rat bone marrow- and blastocyst-derived hypoblast stem cell-like cells. PLoS ONE |
| title | Reversal of hyperglycemia by insulin-secreting rat bone marrow- and blastocyst-derived hypoblast stem cell-like cells. |
| title_full | Reversal of hyperglycemia by insulin-secreting rat bone marrow- and blastocyst-derived hypoblast stem cell-like cells. |
| title_fullStr | Reversal of hyperglycemia by insulin-secreting rat bone marrow- and blastocyst-derived hypoblast stem cell-like cells. |
| title_full_unstemmed | Reversal of hyperglycemia by insulin-secreting rat bone marrow- and blastocyst-derived hypoblast stem cell-like cells. |
| title_short | Reversal of hyperglycemia by insulin-secreting rat bone marrow- and blastocyst-derived hypoblast stem cell-like cells. |
| title_sort | reversal of hyperglycemia by insulin secreting rat bone marrow and blastocyst derived hypoblast stem cell like cells |
| url | http://europepmc.org/articles/PMC3650069?pdf=render |
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