Anchoring of Vascular Endothelial Growth Factor to Surface-Immobilized Heparin on Pancreatic Islets: Implications for Stimulating Islet Angiogenesis

Cabric, Sanja; Sánchez, Javier; Johansson, Ulrika; Larsson, Rolf; Nilsson, Bo; Korsgren, Olle; Magnusson, Peetra U.

doi:10.1089/ten.tea.2009.0429

Cited by 51 publications

(33 citation statements)

References 54 publications

(47 reference statements)

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“…MSCs may influence angiogenesis through several mechanisms. They secrete a range of angiogenic factors, including vascular endothelial growth factor, IL-6, IL-8, haemopoeitic growth factor and platelet-derived growth factor [19,27,30], which are known to enhance islet revascularisation [31][32][33]. In addition, MSCs secrete matrix metalloproteases [14], which facilitate migration of host-derived endothelial cells into the islets [34] degrading the extracellular matrix [35,36].…”

Section: Discussionmentioning

confidence: 99%

Co-transplantation of mesenchymal stem cells maintains islet organisation and morphology in mice

et al. 2011

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Aims/hypothesis Recent studies have shown that mesenchymal stem cells (MSCs) secrete several factors that improve survival and function of transplanted islets. Implantation of islets beneath the kidney capsule results in morphological changes, due to interactions of the graft with the host, thus impairing islet function. We co-transplanted MSCs with islets to determine their effects on the remodelling process and studied graft function in a mouse model of minimal islet mass. Methods Islets were syngeneically transplanted, either alone or with kidney-derived MSCs, underneath the kidney capsule of streptozotocin-induced diabetic C57Bl/6 mice. Blood glucose levels were monitored and intraperitoneal glucose tolerance tests carried out. Hormone contents of grafts and pancreas were assessed by radioimmunoassay. Graft morphology and vascularisation were evaluated by immunohistochemistry. Results MSCs improved the capacity of islet grafts to reverse hyperglycaemia, with 92% of mice co-transplanted with MSCs reverting to normoglycaemia, compared with 42% of those transplanted with islets alone. Average blood glucose concentrations were lower throughout the 1 month monitoring period in MSC co-transplanted mice. MSCs did not alter graft hormone content. Islets co-transplanted with MSCs maintained a morphology that more closely resembled that of islets in the endogenous pancreas, both in terms of size, and of endocrine and endothelial cell distribution. Vascular engraftment was superior in MSC co-transplanted mice, as shown by increased endothelial cell numbers within the endocrine tissue. Conclusions/interpretation Co-transplantation of islets with MSCs had a profound impact on the remodelling process, maintaining islet organisation and improving islet revascularisation. MSCs also improved the capacity of islets to reverse hyperglycaemia.

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Section: Discussionmentioning

confidence: 99%

Co-transplantation of mesenchymal stem cells maintains islet organisation and morphology in mice

et al. 2011

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“…[29][30][31][32][33][34] The use of proangiogenic, degradable hydrogels through the combination of angiogenic growth factors (GFs), such as the plateletderived GF (PDGF-BB) and vascular endothelial GF (VEGF), and biomaterials is an attractive approach that has shown enhanced therapeutic effect over delivery of GF alone. [35][36][37][38] Given the importance of islet revascularization in graft efficacy, we sought to explore the potential use of proangiogenic hydrogels within PDMS scaffolds at an alternative transplant site.…”

mentioning

confidence: 99%

Proangiogenic Hydrogels Within Macroporous Scaffolds Enhance Islet Engraftment in an Extrahepatic Site

Brady

Martino

Pedraza

et al. 2013

Tissue Engineering Part A

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The transplantation of allogeneic islets in recent clinical trials has shown substantial promise as a therapy for type 1 diabetes; however, long-term insulin independence remains inadequate. This has been largely attributed to the current intravascular, hepatic transplant site, which exposes islets to mechanical and inflammatory stresses. A highly macroporous scaffold, housed within an alternative transplant site, can support an ideal environment for islet transplantation by providing three-dimensional distribution of islets, while permitting the infiltration of host vasculature. In the present study, we sought to evaluate the synergistic effect of a proangiogenic hydrogel loaded within the void space of a macroporous poly(dimethylsiloxane) (PDMS) scaffold on islet engraftment. The fibrin-based proangiogenic hydrogel tested presents platelet derived growth factor (PDGF-BB), via a fibronectin (FN) fragment containing growth factor and major integrin binding sites in close proximity. The combination of the proangiogenic hydrogel with PDMS scaffolds resulted in a significant decrease in the time to normoglycemia for syngeneic mouse islet transplants. This benefit was associated with an observed increase in competent vessel branching, as well as mature intraislet vessels. Overall, the addition of the proangiogenic factor PDGF-BB, delivered via the FN fragmentfunctionalized hydrogel, positively influenced the efficiency of engraftment. These characteristics, along with its ease of retrieval, make this combination of a biostable macroporous scaffold and a degradable proangiogenic hydrogel a supportive structure for insulin-producing cells implanted in extrahepatic sites.

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“…According to a number of reports, a VEGF mimetic helical peptide (QK) can bind and activate VEGF receptors to enhance the revascularization process (120). Coverage of islets with an angiogenic growth factor through modification of the islet surface with an anchor molecule attracts endothelial cells and induces islet revascularization (121). Pretreatment of islets with stimulators of vascularization is another strategy (122).…”

Section: Enhancement Of Islet Vasculaturementioning

confidence: 99%

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

Khosravi‐Maharlooei¹,

Hajizadeh‐Saffar²,

Tahamtani³

et al. 2015

European Journal of Endocrinology

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Over the past decades, tremendous efforts have been made to establish pancreatic islet transplantation as a standard therapy for type 1 diabetes. Recent advances in islet transplantation have resulted in steady improvements in the 5-year insulin independence rates for diabetic patients. Here we review the key challenges encountered in the islet transplantation field which include islet source limitation, sub-optimal engraftment of islets, lack of oxygen and blood supply for transplanted islets, and immune rejection of islets. Additionally, we discuss possible solutions for these challenges.

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Anchoring of Vascular Endothelial Growth Factor to Surface-Immobilized Heparin on Pancreatic Islets: Implications for Stimulating Islet Angiogenesis

Cited by 51 publications

References 54 publications

Co-transplantation of mesenchymal stem cells maintains islet organisation and morphology in mice

Co-transplantation of mesenchymal stem cells maintains islet organisation and morphology in mice

Proangiogenic Hydrogels Within Macroporous Scaffolds Enhance Islet Engraftment in an Extrahepatic Site

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

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