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Human β-cell Precursors Mature Into Functional Insulin-producing Cells in an Immunoisolation Device: Implications for Diabetes Cell Therapies

Lee, Seung-Hee1,2; Hao, Ergeng3; Savinov, Alexei Y.4; Geron, Ifat3; Strongin, Alex Y.4; Itkin-Ansari, Pamela1,2,3,5

doi: 10.1097/TP.0b013e31819c86ea
Basic and Experimental Research

Background. Islet transplantation is limited by the need for chronic immunosuppression and the paucity of donor tissue. As new sources of human β-cells are developed (e.g., stem cell-derived tissue), transplanting them in a durable device could obviate the need for immunosuppression, while also protecting the patient from any risk of tumorigenicity. Here, we studied (1) the survival and function of encapsulated human β-cells and their progenitors and (2) the engraftment of encapsulated murine β-cells in allo- and autoimmune settings.

Methods. Human islets and human fetal pancreatic islet-like cell clusters were encapsulated in polytetrafluorethylene devices (TheraCyte) and transplanted into immunodeficient mice. Graft survival and function was measured by immunohistochemistry, circulating human C-peptide levels, and blood glucose levels. Bioluminescent imaging was used to monitor encapsulated neonatal murine islets.

Results. Encapsulated human islet-like cell clusters survived, replicated, and acquired a level of glucose responsive insulin secretion sufficient to ameliorate hyperglycemia in diabetic mice. Bioluminescent imaging of encapsulated murine neonatal islets revealed a dynamic process of cell death followed by regrowth, resulting in robust long-term allograft survival. Further, in the non-obese diabetic (NOD) mouse model of type I diabetes, encapsulated primary β-cells ameliorated diabetes without stimulating a detectable T-cell response.

Conclusions. We demonstrate for the first time that human β-cells function is compatible with encapsulation in a durable, immunoprotective device. Moreover, our study suggests that encapsulation of β-cells before terminal differentiation will be a successful approach for new cell-based therapies for diabetes, such as those derived from stem cells.


1 Development and Aging Program, Burnham Institute for Medical Research, La Jolla, CA.

2 Sanford Children’s Health Research Center, Burnham Institute for Medical Research, La Jolla, CA.

3 Departments of Pediatrics and Moores Cancer Center, University of California, San Diego La Jolla, CA.

4 Infectious and Inflammatory Diseases Program, Burnham Institute for Medical Research, La Jolla, CA.

This work was supported by grants from JDRF and the J. W. Kieckhefer Foundation.

5 Address correspondence to: Pamela Itkin-Ansari, Ph.D., Department of Pediatrics, University of California San Diego, 9500 Gilman Dr, MC 0816, La Jolla, CA 92093-0816.


Received 21 October 2008. Revision requested 12 November 2008.

Accepted 12 December 2008.

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© 2009 Lippincott Williams & Wilkins, Inc.