An Islet-Stabilizing Implant Constructed Using a Preformed Vasculature

Abstract

Islet transplantation for the purpose of treating insulin-sensitive diabetes is currently limited by several factors, including islet survival posttransplantation. In the current study, a tissue-engineered prevascularized pancreatic encapsulating device (PPED) was developed. Isolated islets were placed in collagen gels, and they exhibited fourfold more insulin release than islets not in collagen. The insulin released by beta-cells in islets encapsulated in collagen exhibited unobstructed diffusion within the collagen gels. Subsequent studies evaluated the ability to create a sandwich comprised of two layers of prevascularized collagen gels around a central collagen gel containing islets. In vitro characterization of the islets showed that islets are functional and responded to glucose stimulation. The PPEDs were implanted subcutaneously into severe combined immunodeficient mice. Islet survival was assessed after 7, 14, and 28 days. Immunohistochemical analysis was performed on the implants to detect insulin and the presence of intraislet endothelial cells. At all time points, insulin was localized in association with intact and partially dissociated islets. Moreover, cells that exhibited insulin staining were colocalized with intraislet endothelial cells. These data indicate that the PPED enhances islet survival by supporting islet viability and maintaining intraislet endothelial cell structures.

Experimental approaches to vascularisation within tissue engineering constructs

“…This delay could be reduced by prevascularization of the scaffold prior to implantation, as prevascularized tissue only requires anastomosing with the host vasculature. Scaffolds can be prevascularized by either an in vitro [186,272] or in vivo [273,274] approach. In vitro prevascularization 716 Md.…”

Reduction of diffusion barriers in isolated rat islets improves survival, but not insulin secretion or transplantation outcome

“…2 However, death or nonfunction of a major portion of transplanted islets occurs quickly during or after transplantation, requiring exorbitant quantities of islets from the donor pancreata. 3 While the reasons for the requirement of multiple donors are not completely clear, one contributing factor is the vulnerability of islets immediately after transplantation. 4 …”

THERAPY OF ENDOCRINE DISEASE: Islet transplantation for type 1 diabetes: so close and yet so far away

“…Another possible solution is to prepare a prevascularized site before islet transplantation. A related novel idea is to create a sandwich comprised of two layers of pre-vascularized collagen gels around a central islet containing-collagen gel (130).…”