Macro- or microencapsulation of pig islets to cure type 1 diabetes

Abstract

Although allogeneic islet transplantation can successfully cure type 1 diabetes, it has limited applicability. For example, organs are in short supply; several human pancreas donors are often needed to treat one diabetic recipient; the intrahepatic site may not be the most appropriate site for islet implantation; and immunosuppressive regimens, which are associated with side effects, are often required to prolong survival of the islet graft. An alternative source of insulin-producing cells would therefore be of major interest. Pigs represent a possible alternative source of beta cells. Grafting of pig islets may appear difficult because of the immunologic species barrier, but pig islets have been shown to function in primates for at least 6 mo with clinically incompatible immunosuppression. Therefore, a bioartificial pancreas made of encapsulated pig islets may resolve issues associated with islet allotransplantation. Although several groups have shown that encapsulated pig islets are functional in small-animal models, less is known about the use of bioartificial pancreases in large-animal models. In this review, we summarize current knowledge of encapsulated pig islets, to determine obstacles to implantation in humans and possible solutions to overcome these obstacles.

Tissue Engineering Approaches to Cell-Based Type 1 Diabetes Therapy

“…11 Several preclinical trials using macroor microencapsulation of porcine islets demonstrated efficacy for several years without the need for immunosuppressants. 12 …”

Transplantable bioartificial pancreas devices: current status and future prospects

“…Numerous studies on islet microencapsulation have been published and reviewed on various rodent diabetes models [35,36]. However, this approach has shown limitations in achieving significance within large animals and human clinical trials [37][38][39][40][41][42][43]. The standard islet encapsulating alginate microcapsules are produced by dropwise addition of sodium alginate, mixed with islets, into a bath of CaCl2 or BaCl2, which rapidly crosslinks to form a hydrogel capsule containing the islet.…”

Prospects of Application of Tissue-Engineered Pancreatic Constructs in the Treatment of Type 1 Diabetes

“…Количество доклинических испытаний со свиными островками на людях крайне ограничено, хотя свиные островки сохранялись и функционировали в течение до 6 ме-сяцев у нечеловеческих приматов с применением иммуносупрессии [16]. Несколько доклинических испытаний с использованием макро-или микроин-капсуляции свиных островков продемонстрирова-ли, что их имплантация давала позитивный эффект в течение нескольких лет без использования имму-носупрессии [17]. Тем не менее сохраняется мне-ние о том, что трансплантация островков свиньи остается несовершенным методом лечения в связи с ограниченной долгосрочной жизнеспособностью in vivo и постоянной потребностью в применении иммуносупрессивных препаратов [18].…”