Oxygenation of the Intraportally Transplanted Pancreatic Islet

Abstract

Intraportal islet transplantation (IT) is not widely utilized as a treatment for type 1 diabetes. Oxygenation of the intraportally transplanted islet has not been studied extensively. We present a diffusion-reaction model that predicts the presence of an anoxic core and a larger partly functional core within intraportally transplanted islets. Four variables were studied: islet diameter, islet fractional viability, external oxygen partial pressure (P) (in surrounding portal blood), and presence or absence of a thrombus on the islet surface. Results indicate that an islet with average size and fractional viability exhibits an anoxic volume fraction (AVF) of 14% and a function loss of 72% at a low external P. Thrombus formation increased AVF to 30% and function loss to 92%, suggesting that the effect of thrombosis may be substantial. External P and islet diameter accounted for the greatest overall impact on AVF and loss of function. At our institutions, large human alloislets (>200 μm diameter) account for ~20% of total islet number but ~70% of total islet volume; since most of the total transplanted islet volume is accounted for by large islets, most of the intraportal islet cells are likely to be anoxic and not fully functional.

Human mesenchymal‐stem‐cells‐derived exosomes are important in enhancing porcine islet resistance to hypoxia

“…Instant blood‐mediated inflammatory reaction (IBMIR), which results in possible formation of surface thrombi around the graft, may aggravate poor oxygenation of islets transplanted intra‐portally in the early post‐transplantation period . Up to 70% of the transplanted beta cells may be destroyed during culture and the early stage of post‐transplantation . Therefore, many strategies, including anti‐apoptosis drugs and gene modification, have been tested to improve islet culture conditions to resist hypoxic damage and enhance the function of isolated islets .…”

“…Up to 70% of the transplanted beta cells may be destroyed during culture and the early stage of post-transplantation. 10,11 Therefore, many strategies, including anti-apoptosis drugs and gene modification, have been tested to improve islet culture conditions to resist hypoxic damage and enhance the function of isolated islets. [12][13][14] However, in light of anti-apoptosis drug safety and side effects, the therapeutic effects were not ideal in most of these studies.…”

Update on cellular encapsulation

“…Once tissues are separated from their native vasculature, the transport of nutrients and oxygen relies strictly on diffusion. With the addition of adherent coatings such as in the case of microcapsules, densely packed tissues as in the case of macrocapsules, or with the presence of fibrosis, the distance that nutrients and oxygen must travel to supply the transplanted tissue increases . Therefore, diffusional distances become a limiting factor to the size of encapsulation devices .…”

“…With the addition of adherent coatings such as in the case of microcapsules, densely packed tissues as in the case of macrocapsules, or with the presence of fibrosis, the distance that nutrients and oxygen must travel to supply the transplanted tissue increases . Therefore, diffusional distances become a limiting factor to the size of encapsulation devices . This effect has perhaps been best characterized for pancreatic islets, whose viability and function are critically dependent on adequate oxygenation .…”

“…Therefore, diffusional distances become a limiting factor to the size of encapsulation devices . This effect has perhaps been best characterized for pancreatic islets, whose viability and function are critically dependent on adequate oxygenation . It is estimated that at a surrounding pO 2 of 40 mm Hg, the core of a 100‐μm islet will become anoxic, leading to central necrosis .…”