Encapsulated piscine (tilapia) islets for diabetes therapy: studies in diabetic NOD and NOD‐SCID mice

Abstract

We conclude that microencapsulated tilapia islets can survive long term with excellent metabolic control in diabetic mice given targeted immunosuppression, suggesting that cross-species physiological incompatibility may not compromise the applicability of this novel approach for future clinical applications. We predict that an improved microcapsule that prevents the entrance of IgG will enhance tilapia islet survival in this model, possibly allowing the application of this technique with limited or no immunosuppression.

Bioengineering the Endocrine Pancreas: Intraomental Islet Transplantation Within a Biologic Resorbable Scaffold

“…Suitability of the intraomental biologic scaffold to support islet engraftment under clinically relevant systemic immunosuppressive treatment (32–35) was evaluated in a fully MHC-mismatched allogeneic rat transplant combination. All four diabetic Lewis rat (RT1 l ) recipients of 3,000 IEQ WF islets (RT1 u ) achieved normoglycemia within 5 days and sustained graft function for up to 5 weeks posttransplantation under the transient systemic immunosuppression protocol used, when graft rejection coincided with return to a hyperglycemic state (Fig.…”

“…Clinically relevant immunosuppressive agents were used in both rat and NHP allogeneic transplant models (32–35). Rats received induction treatment with antilymphocyte serum (0.5 mL i.p.…”

“…on day −3 [http://www.accurate.com.gr]) and mycophenolic acid (20 mg/kg/day starting on the day of transplant for 2 weeks then tapered by one-quarter of the dose every 2 days until day 20; Myfortic [https://www.novartis.com]) (36) combined with cytotoxic T-lymphocyte–associated protein-4 (CD152)–immunoglobulin fusion protein (CTLA4Ig) (10 mg/kg i.p. on days 0, 2, 4, 6, 8, and 10 and weekly thereafter; abatacept [Orencia] [http://www.bms.com]), adapted from Safley et al (35). The NHP received anti-thymocyte (rabbit) globulin (10 mg/kg i.v.…”

Ancestral genomic duplication of the insulin gene in tilapia: An analysis of possible implications for clinical islet xenotransplantation using donor islets from transgenic tilapia expressing a humanized insulin gene

“…9 Because of the low metabolic needs of tilapia (n.b., tilapia are evolved to thrive in warm stagnant water nearly devoid of dissolved oxygen), tilapia BBs are an order of magnitude more hypoxia resistant than mammalian islets 10 making them ideal for survival and long-term function within encapsulation devices 11 which can be further prolonged when combined with co-stimulatory blockade. 12,13 Initially, our intent was to use tilapia BBs simply as an inexpensive source of xenogeneic islets to study the mechanism of xenograft rejection and to gain insights into its prevention. However, because of many of the features listed above, we wondered if it might be possible to use them clinically.…”

Re-engineering islet cell transplantation

“…Interestingly, unlike calcium–gelled capsules, barium capsules are intrinsically radiopaque, which could be easily imaged in vivo with micro-computed tomography. Improved survival of xenogeneic islets was demonstrated in the stringent NOD mouse model by combining bariumgelled alginate microcapsules with co-stimulation blockade [150,151]. …”