title: Noninvasive evaluation of the vascular response to transplantation of alginate encapsulated islets using the dorsal skin-fold model.
abstract: Alginate encapsulation reduces the risk of transplant rejection by evading immune-mediated cell injury and rejection; however, poor vascular perfusion results in graft failure. Since existing imaging models are incapable of quantifying the vascular response to biomaterial implants after transplantation, in this study, we demonstrate the use of in vivo laser speckle imaging (LSI) and wide-field functional imaging (WiFI) to monitor the microvascular environment surrounding biomaterial implants. The vascular response to two islet-containing biomaterial encapsulation devices, alginate microcapsules and a high-guluronate alginate sheet, was studied and compared after implantation into the mouse dorsal window chamber (N = 4 per implant group). Images obtained over a 14-day period using LSI and WiFI were analyzed using algorithms to quantify blood flow, hemoglobin oxygen saturation and vascular density. Using our method, we were able to monitor the changes in the peri-implant microvasculature noninvasively without the use of fluorescent dyes. Significant changes in blood flow, hemoglobin oxygen saturation and vascular density were noted as early as the first week post-transplant. The dorsal window chamber model enables comparison of host responses to transplanted biomaterials. Future experiments will study the effect of changes in alginate composition on the vascular and immune responses.
authors.affiliation: Department of Surgery, University of California Irvine, Orange, CA 92868, USA.
authors.forename: Rahul
authors.initials: R
authors.lastname: Krishnan
authors.forename: Rajan P
authors.initials: RP
authors.lastname: Arora
authors.forename: Michael
authors.initials: M
authors.lastname: Alexander
authors.forename: Sean M
authors.initials: SM
authors.lastname: White
authors.forename: Morgan W
authors.initials: MW
authors.lastname: Lamb
authors.forename: Clarence E
authors.initials: CE
authors.lastname: Foster
authors.forename: Bernard
authors.initials: B
authors.lastname: Choi
authors.forename: Jonathan R T
authors.initials: JR
authors.lastname: Lakey
mesh_terms: D000464:Alginates / Q000737:chemistry*; D000818:Animals; D001705:Bioprosthesis; D018914:Cells, Immobilized; D003921:Diabetes Mellitus, Experimental / Q000601:surgery*; D004867:Equipment Design; D020723:Glucuronic Acid / Q000737:chemistry; D006603:Hexuronic Acids / Q000737:chemistry; D007515:Islets of Langerhans / Q000166:cytology*; D016381:Islets of Langerhans Transplantation / Q000295:instrumentation*; D008297:Male; D051379:Mice; D018919:Neovascularization, Physiologic; D013552:Swine
chemical_list: D000464:Alginates; D006603:Hexuronic Acids; D020723:Glucuronic Acid
keywords: AECM; Alginate; Angiogenesis; CITR; Collaborative Islet Transplant Registry; Diabetes; Encapsulation; FVD; Functional Vascular Density; GSIR; HbOS; IEQ; In vivo test; Islet; LSI; MSI; T1D; Transplantation; UP LVM; VD; WiFI; anterior eye chamber model; functional vascular density; glucose stimulated insulin release; hemoglobin oxygen saturation; islet equivalents; laser speckle imaging; multispectral imaging; type 1 diabetes mellitus; ultra-pure low viscous mannuronate; vessel diameter; wide-field functional imaging