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 journalArticle

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

Fingerprint

Germ Layers
Blastocyst
hyperglycemia
Stem cells
blastocyst
Hyperglycemia
bone marrow
stem cells
Rats
Bone
insulin
Stem Cells
Bone Marrow
Insulin
rats
C-Peptide
Endoderm
cells
Insulin-Secreting Cells
Grafts

All Science Journal Classification (ASJC) codes

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

Cite this

Kumar, Anujith ; Lo Nigro, Antonio ; Gysemans, Conny ; Cai, Qing ; Esguerra, Camila ; Nelson-Holte, Molly ; Heremans, Yves ; Jiménez-González, María ; Porciuncula, Angelo ; Mathieu, Chantal ; Binas, Bert ; Heimberg, Harry ; Prosper, Felipe ; Hering, Bernhard ; Verfaillie, Catherine M. ; Barajas, Miguel. / Reversal of Hyperglycemia by Insulin-Secreting Rat Bone Marrow- and Blastocyst-Derived Hypoblast Stem Cell-Like Cells. In: PLoS One. 2013 ; Vol. 8, No. 5.
@article{6d764ff83d4e405a94b2348eb4d4e0c9,
title = "Reversal of Hyperglycemia by Insulin-Secreting Rat Bone Marrow- and Blastocyst-Derived Hypoblast Stem Cell-Like Cells",
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.",
author = "Anujith Kumar and {Lo Nigro}, Antonio and Conny Gysemans and Qing Cai and Camila Esguerra and Molly Nelson-Holte and Yves Heremans and Mar{\'i}a Jim{\'e}nez-Gonz{\'a}lez and Angelo Porciuncula and Chantal Mathieu and Bert Binas and Harry Heimberg and Felipe Prosper and Bernhard Hering and Verfaillie, {Catherine M.} and Miguel Barajas",
year = "2013",
month = "5",
day = "9",
doi = "10.1371/journal.pone.0063491",
language = "English",
volume = "8",
journal = "PLoS One",
issn = "1932-6203",
publisher = "Public Library of Science",
number = "5",

}

Kumar, A, Lo Nigro, A, Gysemans, C, Cai, Q, Esguerra, C, Nelson-Holte, M, Heremans, Y, Jiménez-González, M, Porciuncula, A, Mathieu, C, Binas, B, Heimberg, H, Prosper, F, Hering, B, Verfaillie, CM & Barajas, M 2013, 'Reversal of Hyperglycemia by Insulin-Secreting Rat Bone Marrow- and Blastocyst-Derived Hypoblast Stem Cell-Like Cells', PLoS One, vol. 8, no. 5, e63491. https://doi.org/10.1371/journal.pone.0063491

Reversal of Hyperglycemia by Insulin-Secreting Rat Bone Marrow- and Blastocyst-Derived Hypoblast Stem Cell-Like Cells. / Kumar, Anujith; Lo Nigro, Antonio; Gysemans, Conny; Cai, Qing; Esguerra, Camila; Nelson-Holte, Molly; Heremans, Yves; Jiménez-González, María; Porciuncula, Angelo; Mathieu, Chantal; Binas, Bert; Heimberg, Harry; Prosper, Felipe; Hering, Bernhard; Verfaillie, Catherine M.; Barajas, Miguel.

In: PLoS One, Vol. 8, No. 5, e63491, 09.05.2013.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Reversal of Hyperglycemia by Insulin-Secreting Rat Bone Marrow- and Blastocyst-Derived Hypoblast Stem Cell-Like Cells

AU - Kumar, Anujith

AU - Lo Nigro, Antonio

AU - Gysemans, Conny

AU - Cai, Qing

AU - Esguerra, Camila

AU - Nelson-Holte, Molly

AU - Heremans, Yves

AU - Jiménez-González, María

AU - Porciuncula, Angelo

AU - Mathieu, Chantal

AU - Binas, Bert

AU - Heimberg, Harry

AU - Prosper, Felipe

AU - Hering, Bernhard

AU - Verfaillie, Catherine M.

AU - Barajas, Miguel

PY - 2013/5/9

Y1 - 2013/5/9

N2 - 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.

AB - 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.

UR - http://www.scopus.com/inward/record.url?scp=84877359939&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84877359939&partnerID=8YFLogxK

U2 - 10.1371/journal.pone.0063491

DO - 10.1371/journal.pone.0063491

M3 - Article

VL - 8

JO - PLoS One

JF - PLoS One

SN - 1932-6203

IS - 5

M1 - e63491

ER -