Skip Navigation LinksHome > September 15, 2014 - Volume 98 - Issue 5 > Therapeutic Effects of a Non–β Cell Bioartificial Pancreas i...
Transplantation:
doi: 10.1097/TP.0000000000000247
Basic and Experimental Research

Therapeutic Effects of a Non–β Cell Bioartificial Pancreas in Diabetic Mice

Tiernan, Aubrey R.1; Thulé, Peter M.2; Sambanis, Athanassios1,3,4

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Abstract

Background

Cell-based insulin therapies can potentially improve glycemic regulation in insulin-dependent diabetic patients. Enteroendocrine cells engineered to secrete recombinant insulin have exhibited glycemic efficacy, but have been primarily studied as uncontrollable growth systems in immune incompetent mice. Furthermore, reports suggest that suboptimal insulin secretion remains a barrier to expanded application.

Methods

Genetic and tissue engineering strategies were applied to improve recombinant insulin secretion from intestinal L-cells on both a per-cell and per-graft basis. Transduction of insulin-expressing GLUTag L-cells with lentivirus carrying an additional human insulin gene–enhanced secretion twofold. We infected cells with lentivirus expressing a luciferase reporter gene to track cell survival in vivo. To provide a growth-controlled and immune protective environment without affecting secretory capacity, cells were microencapsulated in barium alginate. Approximately 9×107 microencapsulated cells were injected intraperitoneally in immune competent streptozotocin-induced diabetic mice for therapeutic efficacy evaluation.

Results

Graft insulin secretion was increased to 16 to 24 mU insulin per day. Transient normoglycemia was achieved in treated mice two days after transplantation, and endogenous insulin was sufficient to sustain body weights of treated mice receiving minimal supplementation.

Conclusion

Glycemic efficacy of a bioartificial pancreas based on insulin-secreting enteroendocrine cells is insufficient as a standalone therapy, despite enhancement of graft insulin secretion capacity. Supplemental strategies to alleviate secretion limitations should be pursued.

Copyright © 2014 by Lippincott Williams & Wilkins

 

 

 

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