Subcutaneous Pancreatic Islet Transplantation Using Fibrin Glue as a Carrier

Andrades, Patricio; Asiedu, Clement; Rodriguez, Christina M.; Goodwin, Karen; McCarn, J.; Thomas, Judith M.

doi:10.1016/j.transproceed.2006.10.019

Cited by 28 publications

(22 citation statements)

References 6 publications

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“…Recent rodent studies on islet transplantation suggest that it might be possible to use s.c. sites for implantation (27). Such a noninvasive mode of transplantation could enable continuous monitoring of the implant growth and will avoid the potential risk of developing sclerosing encapsulating peritonitis that might arise (as suspected in animal #4) upon infection or graft rejection at the omental site.…”

Section: Discussionmentioning

confidence: 99%

Embryonic pig pancreatic tissue for the treatment of diabetes in a nonhuman primate model

Hecht

Eventov‐Friedman

Rosen

et al. 2009

Proc. Natl. Acad. Sci. U.S.A.

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Xenotransplantation of pig tissues has great potential to overcome the shortage of organ donors. One approach to address the vigorous immune rejection associated with xenotransplants is the use of embryonic precursor tissue, which induces and utilizes host vasculature upon its growth and development. Recently, we showed in mice that embryonic pig pancreatic tissue from embryonic day 42 (E42) exhibits optimal properties as a ␤ cell replacement therapy. We now demonstrate the proof of concept in 2 diabetic Cynomolgus monkeys, followed for 393 and 280 days, respectively. A marked reduction of exogenous insulin requirement was noted by the fourth month after transplantation, reaching complete independence from exogenous insulin during the fifth month after transplantation, with full physiological control of blood glucose levels. The porcine origin of insulin was documented by a radioimmunoassay specific for porcine C-peptide. Furthermore, the growing tissue was found to be predominantly vascularized with host blood vessels, thereby evading hyperacute or acute rejection, which could potentially be mediated by preexisting anti-pig antibodies. Durable graft protection was achieved, and most of the late complications could be attributed to the immunosuppressive protocol. While fine tuning of immune suppression, tissue dose, and implantation techniques are still required, our results demonstrate that porcine E-42 embryonic pancreatic tissue can normalize blood glucose levels in primates. Its long-term proliferative capacity, its revascularization by host endothelium, and its reduced immunogenicity, strongly suggest that this approach could offer an attractive replacement therapy for diabetes.immune-suppression ͉ rejection ͉ xeno-transplantation

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Section: Discussionmentioning

confidence: 99%

Embryonic pig pancreatic tissue for the treatment of diabetes in a nonhuman primate model

Hecht

Eventov‐Friedman

Rosen

et al. 2009

Proc. Natl. Acad. Sci. U.S.A.

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show abstract

“…Beattie et al [161] have shown that entrapment in a 3-D fibrin matrix support remarkably improves survival, reduces apoptosis, and allows for Hepatocyte Growth Factor (HGF) mediated proliferation of the islet cells without loss of function, while preserving physiologic glucose responsiveness both in vitro and in vivo after transplantation into nude mice. Andrades et al [162] showed that pancreatic β-cells seeded into the FG and implanted subcutaneously in the streptozotocin-induced diabetic mice achieved same level of blood sugar during 4 weeks of monitoring as those in which an islet suspension graft, necessitating elaborate preparation procedure, was placed under the kidney capsule. In a very recent study, Najjar et al [163] employed fibrin matrices rendered pro-angiogenic by incorporation of vascular endothelial growth factor-A165 and plateletderived growth factor-BB for pancreatic islet transplantation in mice.…”

Section: Delivery Of Antigensmentioning

confidence: 99%

Fibrin matrices: The versatile therapeutic delivery systems

Ahmad

Fatima

Hoque

et al. 2015

International Journal of Biological Macromolecules

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“…In an in vitro three-dimensional culture system, fibrin glue was demonstrated to facilitate an increase of beta-cell mass while preserving normal function [21]. In preliminary studies, fibrin has been suggested to be a carrier for islet transplantation into the subcutaneous pocket [22,23]. However, major obstacle in the clinical application of fibrin as an islet carrier into the subcutaneous pocket is that there are no optimized protocols of the fibrin-islet composites in vivo to enable the implanted islets to achieve rapid glycemic control with a minimum amount of islets.…”

Section: Introductionmentioning

confidence: 99%