Transplantation of Human Pancreatic Endoderm Cells Reverses Diabetes Post Transplantation in a Prevascularized Subcutaneous Site

Andrew R. Pepper; Rena Pawlick; Antonio Bruni; John Wink; Yasmin Rafiei; Doug O'Gorman; Richard Yan-Do; Boris Gala-Lopez; Tatsuya Kin; Patrick E. MacDonald; A. M.James Shapiro

doi:10.1016/j.stemcr.2017.05.004

Transplantation of Human Pancreatic Endoderm Cells Reverses Diabetes Post Transplantation in a Prevascularized Subcutaneous Site

Andrew R. Pepper, Rena Pawlick, Antonio Bruni, John Wink, Yasmin Rafiei, Doug O'Gorman, Richard Yan-Do, Boris Gala-Lopez, Tatsuya Kin, Patrick E. MacDonald, A. M.James Shapiro

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73 Citas (Scopus)

Resumen

Beta-cell replacement therapy is an effective means to restore glucose homeostasis in select humans with autoimmune diabetes. The scarcity of “healthy” human donor pancreata restricts the broader application of this effective curative therapy. “β-Like” cells derived from human embryonic stem cells (hESC), with the capacity to secrete insulin in a glucose-regulated manner, have been developed in vitro, with limitless capacity for expansion. Here we report long-term diabetes correction in mice transplanted with hESC-derived pancreatic endoderm cells (PECs) in a prevascularized subcutaneous site. This advancement mitigates chronic foreign-body response, utilizes a device- and growth factor-free approach, facilitates in vivo differentiation of PECs into glucose-responsive insulin-producing cells, and reliably restores glycemic control. Basal and stimulated human C-peptide secretion was detected throughout the study, which was abolished upon graft removal. Recipient mice demonstrated physiological clearance of glucose in response to metabolic challenge and safely retrieved grafts contained viable glucose regulatory cells.

Idioma original	English
Páginas (desde-hasta)	1689-1700
Número de páginas	12
Publicación	Stem Cell Reports
Volumen	8
N.º	6
DOI	https://doi.org/10.1016/j.stemcr.2017.05.004
Estado	Published - jun. 6 2017
Publicado de forma externa	Sí

Nota bibliográfica

Funding Information:
We thank the Clinical Islet Laboratory and Alberta Health Services for providing human islet research preparations. This work was supported in part by the Diabetes Research Institute Foundation of Canada (DRIFCan), Collaborative Research & Innovation Opportunities – Alberta Innovates Healthcare Solutions (AIHS) & Canadian Institutes of Health Research – Proof of Principle. All authors are members of the Alberta Diabetes Institute and of the Canadian National Transplant Research Program (CNTRP). A.M.J.S. is supported through a Canada Research Chair (CRC) in Transplantation Surgery and Regenerative Medicine, and through a Senior Clinical Scholarship from AIHS. A.R.P. is supported by an AIHS Postdoctoral fellowship. A.B. is supported by scholarships from the University of Alberta and the Alberta Diabetes Institute. P.E.M. holds a Killam Annual Professorship. We also thank ViaCyte, Inc. for kindly providing the PECs. A.M.J.S. serves as an advisor to ViaCyte Inc. with respect to design and testing on ongoing clinical and experimental trials of stem cell products. The Governors of The University of Alberta have filed patent applications with the Canadian Intellectual Property Office (CA.2865122) and the United States Patent and Trademark Office (US 14/863541) pertaining to the DL transplant technology.

Publisher Copyright:
© 2017 The Authors

ASJC Scopus Subject Areas

Biochemistry
Genetics
Developmental Biology
Cell Biology

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Journal Article

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title = "Transplantation of Human Pancreatic Endoderm Cells Reverses Diabetes Post Transplantation in a Prevascularized Subcutaneous Site",

abstract = "Beta-cell replacement therapy is an effective means to restore glucose homeostasis in select humans with autoimmune diabetes. The scarcity of “healthy” human donor pancreata restricts the broader application of this effective curative therapy. “β-Like” cells derived from human embryonic stem cells (hESC), with the capacity to secrete insulin in a glucose-regulated manner, have been developed in vitro, with limitless capacity for expansion. Here we report long-term diabetes correction in mice transplanted with hESC-derived pancreatic endoderm cells (PECs) in a prevascularized subcutaneous site. This advancement mitigates chronic foreign-body response, utilizes a device- and growth factor-free approach, facilitates in vivo differentiation of PECs into glucose-responsive insulin-producing cells, and reliably restores glycemic control. Basal and stimulated human C-peptide secretion was detected throughout the study, which was abolished upon graft removal. Recipient mice demonstrated physiological clearance of glucose in response to metabolic challenge and safely retrieved grafts contained viable glucose regulatory cells.",

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note = "Funding Information: We thank the Clinical Islet Laboratory and Alberta Health Services for providing human islet research preparations. This work was supported in part by the Diabetes Research Institute Foundation of Canada (DRIFCan), Collaborative Research & Innovation Opportunities – Alberta Innovates Healthcare Solutions (AIHS) & Canadian Institutes of Health Research – Proof of Principle. All authors are members of the Alberta Diabetes Institute and of the Canadian National Transplant Research Program (CNTRP). A.M.J.S. is supported through a Canada Research Chair (CRC) in Transplantation Surgery and Regenerative Medicine, and through a Senior Clinical Scholarship from AIHS. A.R.P. is supported by an AIHS Postdoctoral fellowship. A.B. is supported by scholarships from the University of Alberta and the Alberta Diabetes Institute. P.E.M. holds a Killam Annual Professorship. We also thank ViaCyte, Inc. for kindly providing the PECs. A.M.J.S. serves as an advisor to ViaCyte Inc. with respect to design and testing on ongoing clinical and experimental trials of stem cell products. The Governors of The University of Alberta have filed patent applications with the Canadian Intellectual Property Office (CA.2865122) and the United States Patent and Trademark Office (US 14/863541) pertaining to the DL transplant technology. Publisher Copyright: {\textcopyright} 2017 The Authors",

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Transplantation of Human Pancreatic Endoderm Cells Reverses Diabetes Post Transplantation in a Prevascularized Subcutaneous Site

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PubMed: MeSH publication types

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