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Long-term metabolic control of autoimmune diabetes in spontaneously diabetic nonobese diabetic mice by nonvascularized microencapsulated adult porcine islets.
Transplantation. 2009 Jul 27; 88(2):160-9.T

Abstract

BACKGROUND

The long-term metabolic function of microencapsulated xenogeneic adult porcine islets (API) was assessed in a murine model of type 1 diabetes mellitus.

METHODS

API were encapsulated in barium-gelled alginate and transplanted intraperitoneally in diabetic nonobese diabetic (NOD) mice given no immunosuppression or given costimulatory blockade (CoB; CTLA4-Ig+anti-CD154 mAb). Control mice received nonencapsulated API under the kidney capsule. Graft function was monitored by measurement of random blood glucose levels, serum glycosylated hemoglobin (HbA1c), serum porcine C peptide, in vivo glucose tolerance tests, and histologic analyses of host pancreas and graft biopsies. Host immune responses to the islet xenografts were characterized by phenotyping peritoneal cellular infiltrates and by measuring serum antiporcine antibody levels.

RESULTS

Without immunosuppression, nonencapsulated API functioned for less than 1 week, and microencapsulated API functioned for 35+/-14 days before rejection, associated with both a cellular and a humoral immune response. With continuous CoB, nonencapsulated API functioned for 27+/-4 days, whereas microencapsulated API functioned for >450 days with measurable levels of serum porcine C peptide, near normal in vivo glucose tolerance tests and HbA1c levels, and intact microcapsules containing viable, insulin-positive porcine islets.

CONCLUSIONS

Microencapsulated API restored normoglycemia for more than 1 year in spontaneously diabetic NODs given dual CoB. To our knowledge, this is the first study to document long-term normalized HbA1c, porcine C peptide, and near normal glucose tolerance in immunosuppressed diabetic NOD mice transplanted intraperitoneally with microencapsulated API. Our study suggests that transplantation of microencapsulated porcine islet xenografts may be a future treatment for patients with type 1 diabetes mellitus.

Authors+Show Affiliations

Department of Surgery, Emory University, Atlanta, GA 30322, USA.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

19623010

Citation

Cui, Hong, et al. "Long-term Metabolic Control of Autoimmune Diabetes in Spontaneously Diabetic Nonobese Diabetic Mice By Nonvascularized Microencapsulated Adult Porcine Islets." Transplantation, vol. 88, no. 2, 2009, pp. 160-9.
Cui H, Tucker-Burden C, Cauffiel SM, et al. Long-term metabolic control of autoimmune diabetes in spontaneously diabetic nonobese diabetic mice by nonvascularized microencapsulated adult porcine islets. Transplantation. 2009;88(2):160-9.
Cui, H., Tucker-Burden, C., Cauffiel, S. M., Barry, A. K., Iwakoshi, N. N., Weber, C. J., & Safley, S. A. (2009). Long-term metabolic control of autoimmune diabetes in spontaneously diabetic nonobese diabetic mice by nonvascularized microencapsulated adult porcine islets. Transplantation, 88(2), 160-9. https://doi.org/10.1097/TP.0b013e3181abbfc1
Cui H, et al. Long-term Metabolic Control of Autoimmune Diabetes in Spontaneously Diabetic Nonobese Diabetic Mice By Nonvascularized Microencapsulated Adult Porcine Islets. Transplantation. 2009 Jul 27;88(2):160-9. PubMed PMID: 19623010.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Long-term metabolic control of autoimmune diabetes in spontaneously diabetic nonobese diabetic mice by nonvascularized microencapsulated adult porcine islets. AU - Cui,Hong, AU - Tucker-Burden,Carol, AU - Cauffiel,Sean M D, AU - Barry,Adrienne K, AU - Iwakoshi,Neal N, AU - Weber,Collin J, AU - Safley,Susan A, PY - 2009/7/23/entrez PY - 2009/7/23/pubmed PY - 2009/9/17/medline SP - 160 EP - 9 JF - Transplantation JO - Transplantation VL - 88 IS - 2 N2 - BACKGROUND: The long-term metabolic function of microencapsulated xenogeneic adult porcine islets (API) was assessed in a murine model of type 1 diabetes mellitus. METHODS: API were encapsulated in barium-gelled alginate and transplanted intraperitoneally in diabetic nonobese diabetic (NOD) mice given no immunosuppression or given costimulatory blockade (CoB; CTLA4-Ig+anti-CD154 mAb). Control mice received nonencapsulated API under the kidney capsule. Graft function was monitored by measurement of random blood glucose levels, serum glycosylated hemoglobin (HbA1c), serum porcine C peptide, in vivo glucose tolerance tests, and histologic analyses of host pancreas and graft biopsies. Host immune responses to the islet xenografts were characterized by phenotyping peritoneal cellular infiltrates and by measuring serum antiporcine antibody levels. RESULTS: Without immunosuppression, nonencapsulated API functioned for less than 1 week, and microencapsulated API functioned for 35+/-14 days before rejection, associated with both a cellular and a humoral immune response. With continuous CoB, nonencapsulated API functioned for 27+/-4 days, whereas microencapsulated API functioned for >450 days with measurable levels of serum porcine C peptide, near normal in vivo glucose tolerance tests and HbA1c levels, and intact microcapsules containing viable, insulin-positive porcine islets. CONCLUSIONS: Microencapsulated API restored normoglycemia for more than 1 year in spontaneously diabetic NODs given dual CoB. To our knowledge, this is the first study to document long-term normalized HbA1c, porcine C peptide, and near normal glucose tolerance in immunosuppressed diabetic NOD mice transplanted intraperitoneally with microencapsulated API. Our study suggests that transplantation of microencapsulated porcine islet xenografts may be a future treatment for patients with type 1 diabetes mellitus. SN - 1534-6080 UR - https://www.unboundmedicine.com/medline/citation/19623010/Long_term_metabolic_control_of_autoimmune_diabetes_in_spontaneously_diabetic_nonobese_diabetic_mice_by_nonvascularized_microencapsulated_adult_porcine_islets_ L2 - https://doi.org/10.1097/TP.0b013e3181abbfc1 DB - PRIME DP - Unbound Medicine ER -