Emerging technologies in regenerative medicine have the potential to restore the b-cell compartment in diabetic patients, thereby overcoming the inadequacies of current treatment strategies and organ supply. Novel approaches include: 1) Encapsulation technology that protects islet transplants from host immune surveillance; 2) stem cell therapies and cellular reprogramming, which seek to regenerate the depleted b-cell compartment; and 3) whole-organ bioengineering, which capitalizes on the innate properties of the pancreas extracellular matrix to drive cellular repopulation. Collaborative efforts across these subfields of regenerative medicine seek to ultimately produce a bioengineered pancreas capable of restoring endocrine function in patients with insulin-dependent diabetes.Regenerative medicine promises to contribute to the advancement of b-cell replacement strategies through the development and implementation of microencapsulation technology, the production of insulin-producing cells either by regeneration from endogenous cells or reprogramming from nonendocrine adult cell sources, and, more recently, the exploitation of bioengineered microenvironments (1). Considering the shortage of available pancreata, the search for alternative cell sources has recently been categorized within one of the following three "Rs" of pancreatic b-cell replenishment: replacement (from stem cells or xenoislets), regeneration (from endogenous progenitor cells), and reprogramming (from nonendocrine adult cell sources) (2).The purpose of this article is to comprehensively and critically review the main regenerative medicine2based strategies that are currently being developed to treat type 1 diabetes. The first part of the article will illustrate and discuss islet encapsulation technology, which has been extensively investigated over the past 40 years (3) and represents one of the most promising regenerative medicine2based approaches to achieve immunoisolation of transplantable organs. The second part will focus on cell bioengineering, where different types of progenitor and differentiated cell sources are manipulated to ultimately yield insulin-producing cells. The last part of the article will summarize the most recent advancements in the study of the pancreatic extracellular matrix (ECM) as a platform for endocrine pancreas bioengineering.
ISLET ENCAPSULATION TECHNOLOGYEncapsulation technology has been used to protect islets from the host immune system. This strategy holds the promise to allow implantation of islets without immunosuppression not only across genetically different individuals from the same species, but also across species barriers.
MicroencapsulationThe first approach to immunoisolate cells consists of the microencapsulation of one to three islets per semipermeable immunoprotective capsule. The spherical configuration of these microcapsules results in a higher surface-tovolume ratio and a higher diffusion rate (4). Furthermore, microcapsules can be injected in large numbers, are durable, and are difficult to disrup...