Human iPS cell-derived insulin producing cells form vascularized organoids under the kidney capsules of diabetic mice

Sudhanshu P Raikwar; Eun-Mi Kim; William I Sivitz; Chantal Allamargot; Daniel R Thedens; Nicholas Zavazava

doi:10.1371/journal.pone.0116582

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Human iPS cell-derived insulin producing cells form vascularized organoids under the kidney capsules of diabetic mice

Journal article

Open access

Peer reviewed

Human iPS cell-derived insulin producing cells form vascularized organoids under the kidney capsules of diabetic mice

Sudhanshu P Raikwar, Eun-Mi Kim, William I Sivitz, Chantal Allamargot, Daniel R Thedens and Nicholas Zavazava

PloS one, Vol.10(1), pp.e0116582-e0116582

2015

DOI: 10.1371/journal.pone.0116582

PMCID: PMC4309616

PMID: 25629318

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Abstract

Type 1 diabetes (T1D) is caused by autoimmune disease that leads to the destruction of pancreatic β-cells. Transplantation of cadaveric pancreatic organs or pancreatic islets can restore normal physiology. However, there is a chronic shortage of cadaveric organs, limiting the treatment of the majority of patients on the pancreas transplantation waiting list. Here, we hypothesized that human iPS cells can be directly differentiated into insulin producing cells (IPCs) capable of secreting insulin. Using a series of pancreatic growth factors, we successfully generated iPS cells derived IPCs. Furthermore, to investigate the capability of these cells to secrete insulin in vivo, the differentiated cells were transplanted under the kidney capsules of diabetic immunodeficient mice. Serum glucose levels gradually declined to either normal or near normal levels over 150 days, suggesting that the IPCs were secreting insulin. In addition, using MRI, a 3D organoid appeared as a white patch on the transplanted kidneys but not on the control kidneys. These organoids showed neo-vascularization and stained positive for insulin and glucagon. All together, these data show that a pancreatic organ can be created in vivo providing evidence that iPS cells might be a novel option for the treatment of T1D.

Cell Differentiation

Magnetic Resonance Imaging

Animals

Blood Glucose

Diabetes Mellitus, Experimental - metabolism

Diabetes Mellitus, Experimental - therapy

Humans

Induced Pluripotent Stem Cells - cytology

Induced Pluripotent Stem Cells - metabolism

Induced Pluripotent Stem Cells - ultrastructure

Insulin-Secreting Cells - cytology

Insulin-Secreting Cells - metabolism

Male

Mice

Mice, Knockout

Mitochondria - metabolism

Neovascularization, Physiologic

Organoids

Oxygen Consumption

Stem Cell Transplantation

Details

Title: Subtitle: Human iPS cell-derived insulin producing cells form vascularized organoids under the kidney capsules of diabetic mice
Creators: Sudhanshu P Raikwar - University of Iowa
Eun-Mi Kim - University of Iowa
William I Sivitz - University of Iowa
Chantal Allamargot - University of Iowa
Daniel R Thedens - University of Iowa
Nicholas Zavazava - University of Iowa
Resource Type: Journal article
Publication Details: PloS one, Vol.10(1), pp.e0116582-e0116582
DOI: 10.1371/journal.pone.0116582
PMID: 25629318
PMCID: PMC4309616
NLM abbreviation: PLoS One
ISSN: 1932-6203
eISSN: 1932-6203
Grant note: I01 BX000285 / BLRD VA R01 HLO73015 / PHS HHS P30 DK054759 / NIDDK NIH HHS R01 HL073015 / NHLBI NIH HHS I01 BX001125 / BLRD VA
Language: English
Date published: 2015
Academic Unit: Roy J. Carver Department of Biomedical Engineering; Radiology; Electrical and Computer Engineering; Core Research Facilities; Fraternal Order of Eagles Diabetes Research Center; Endocrinology and Metabolism; Internal Medicine
Record Identifier: 9984197914902771

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