A prevascularized subcutaneous device-less site for islet and cellular transplantation

Andrew R. Pepper; Boris Gala-Lopez; Rena Pawlick; Shaheed Merani; Tatsuya Kin; A. M.James Shapiro

doi:10.1038/nbt.3211

A prevascularized subcutaneous device-less site for islet and cellular transplantation

Andrew R. Pepper, Boris Gala-Lopez, Rena Pawlick, Shaheed Merani, Tatsuya Kin, A. M.James Shapiro

Research output: Contribution to journal › Article › peer-review

314 Citations (Scopus)

Abstract

Transplantation of donor-derived islets into the liver is a successful cellular replacement therapy for individuals with diabetes. However, the hepatic vasculature is not an optimal transplant site for several reasons, including graft attrition and the inability to retrieve or image the islets. Here we describe islet transplantation into a prevascularized, subcutaneous site created by temporary placement of a medically approved vascular access catheter. In mice with streptozotocin (STZ)-induced diabetes, transplantation of ∼500 syngeneic islets into the resulting 'device-less' space reversed diabetes in 91% of mice and maintained normoglycemia for >100 days. The approach was also effective in mice with pre-existing diabetes, in another mouse strain that mounts a more vigorous inflammatory response, and across an allogeneic barrier. These results demonstrate that transient priming of a subcutaneous site supports diabetes-reversing islet transplantation in mouse models without the need for a permanent cell-encapsulation device.

Original language	English
Pages (from-to)	518-523
Number of pages	6
Journal	Nature Biotechnology
Volume	33
Issue number	5
DOIs	https://doi.org/10.1038/nbt.3211
Publication status	Published - May 12 2015
Externally published	Yes

Bibliographical note

Funding Information:
The authors thank H. Tanaka for Figure 1. 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, Collaborative Research & Innovation Opportunities (CRIO)–Alberta Innovates Healthcare Solutions, and from University Hospital Foundation/C.F. “Curly” and Gladys B. MacLachlan Fund. All authors are members of the Alberta Diabetes Institute, and of the Canadian National Transplant Research Program. A.M.J.S. is supported through a Canada Research Chair in Transplantation Surgery and Regenerative Medicine, and through a Senior Clinical Scholarship from Alberta Innovates Healthcare Solutions.

Publisher Copyright:
© 2015 Nature America, Inc. All rights reserved.

ASJC Scopus Subject Areas

Biotechnology
Bioengineering
Applied Microbiology and Biotechnology
Molecular Medicine
Biomedical Engineering

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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10.1038/nbt.3211

Cite this

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abstract = "Transplantation of donor-derived islets into the liver is a successful cellular replacement therapy for individuals with diabetes. However, the hepatic vasculature is not an optimal transplant site for several reasons, including graft attrition and the inability to retrieve or image the islets. Here we describe islet transplantation into a prevascularized, subcutaneous site created by temporary placement of a medically approved vascular access catheter. In mice with streptozotocin (STZ)-induced diabetes, transplantation of ∼500 syngeneic islets into the resulting 'device-less' space reversed diabetes in 91% of mice and maintained normoglycemia for >100 days. The approach was also effective in mice with pre-existing diabetes, in another mouse strain that mounts a more vigorous inflammatory response, and across an allogeneic barrier. These results demonstrate that transient priming of a subcutaneous site supports diabetes-reversing islet transplantation in mouse models without the need for a permanent cell-encapsulation device.",

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A prevascularized subcutaneous device-less site for islet and cellular transplantation

Abstract

Bibliographical note

ASJC Scopus Subject Areas

UN SDGs

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