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

Producción científica: Contribución a una revistaArtículorevisión exhaustiva

314 Citas (Scopus)

Resumen

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.

Idioma originalEnglish
Páginas (desde-hasta)518-523
Número de páginas6
PublicaciónNature Biotechnology
Volumen33
N.º5
DOI
EstadoPublished - may. 12 2015
Publicado de forma externa

Nota bibliográfica

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

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