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Oligomeric collagen as an encapsulation material for islet/β-cell replacement: effect of islet source, dose, implant site, and administration format.
- Source :
-
American journal of physiology. Endocrinology and metabolism [Am J Physiol Endocrinol Metab] 2020 Aug 01; Vol. 319 (2), pp. E388-E400. Date of Electronic Publication: 2020 Jun 16. - Publication Year :
- 2020
-
Abstract
- Replacement of islets/β-cells that provide long-lasting glucose-sensing and insulin-releasing functions has the potential to restore extended glycemic control in individuals with type 1 diabetes. Unfortunately, persistent challenges preclude such therapies from widespread clinical use, including cumbersome administration via portal vein infusion, significant loss of functional islet mass upon administration, limited functional longevity, and requirement for systemic immunosuppression. Previously, fibril-forming type I collagen (oligomer) was shown to support subcutaneous injection and in situ encapsulation of syngeneic islets within diabetic mice, with rapid (<24 h) reversal of hyperglycemia and maintenance of euglycemia for beyond 90 days. Here, we further evaluated this macroencapsulation strategy, defining effects of islet source (allogeneic and xenogeneic) and dose (500 and 800 islets), injection microenvironment (subcutaneous and intraperitoneal), and macrocapsule format (injectable and preformed implantable) on islet functional longevity and recipient immune response. We found that xenogeneic rat islets functioned similarly to or better than allogeneic mouse islets, with only modest improvements in longevity noted with dosage. Additionally, subcutaneous injection led to more consistent encapsulation outcomes along with improved islet health and longevity, compared with intraperitoneal administration, whereas no significant differences were observed between subcutaneous injectable and preformed implantable formats. Collectively, these results document the benefits of incorporating natural collagen for islet/β-cell replacement therapies.
- Subjects :
- Allografts
Animals
Blood Glucose analysis
Cell Survival
Diabetes Mellitus, Experimental therapy
Diabetes Mellitus, Type 1 blood
Graft Survival
Heterografts
Injections, Intraperitoneal
Injections, Subcutaneous
Insulin-Secreting Cells physiology
Insulin-Secreting Cells transplantation
Islets of Langerhans physiology
Mice
Mice, Inbred C57BL
Rats
Rats, Sprague-Dawley
Cell Encapsulation methods
Collagen chemistry
Diabetes Mellitus, Type 1 therapy
Islets of Langerhans Transplantation methods
Subjects
Details
- Language :
- English
- ISSN :
- 1522-1555
- Volume :
- 319
- Issue :
- 2
- Database :
- MEDLINE
- Journal :
- American journal of physiology. Endocrinology and metabolism
- Publication Type :
- Academic Journal
- Accession number :
- 32543944
- Full Text :
- https://doi.org/10.1152/ajpendo.00066.2020