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Successful
reversal of spontaneous diabetes in dogs by intraperitoneal
microencapsulated islets
Soon-Shiong, P., Feldman, E., Nelson, R., Komtebedde, J. Abstract
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Abstract
Long-term euglycemia by intraperitoneal transplantation of microencapsulated
islets has not been described in the diabetic large animal model. In this
study, we report the successful long-term reversal of diabetes by this method
in spontaneous diabetic dogs. We have identified fundamental mechanism(s)
associated with alginate-based microcapsule fibrosis, and have devised methods
to ameliorate this problem. These include the use of purified alginate of low
mannuronic acid content and cytokine suppression. Ten insulin-dependent,
spontaneous diabetic dogs (insulin requirement 1-4 units/kg/day; absence of
circulating C-peptide and diabetic K values of 0.6 +- 0.4) were entered into
the study. Islets from mongrel donor pancreata were isolated and transplanted
intraperitoneally either as free islet controls (n=3) or as microencapsulated
islet allografts (n=7). In all seven encapsulted islet recipients, euglycemia
was achieved within 24 hr (serum glucose failing from 304 +- 117 to 116 +- 72
mg/dl). IVGTT performed 14 days after islet transplant demonstrated
normalization of K-values changing from a pretransplant level of 0.6 +- 0.4 to
2.6 +- 0.6. All animals receiving encapsulated islets remained euglycemic,
free of the need for exogenous insulin, for a period of 63-172 days, with a
median insulin-independence for 105 days. In contrast, recipients receiving
free islets rejected their graft within seven days of implantation. In
conclusion, this is the first report of long-term successful reversal of
spontaneous diabetes in the large animal model by an intraperitoneal injection
of encapsulated islets. The potential exists for this form of therapy to be
explored in the treatment of type I diabetes in man.
Reference
Transplantation , 54(5):769 1992
Updated January 2016
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