Vascularization of the Pancreas: An Evolving Role From Embryogenesis to Adulthood

Duvillié, Bertrand

doi:10.2337/db13-1421

Cited by 9 publications

(6 citation statements)

References 16 publications

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“…It is well known that the omentum is a highly vascularized tissue with endogenous angiogenic factors [41], and it appears that the ambient vascularity of the omentum provides adequate supply of nutrients and oxygen to the islet transplants. The lack of effect of enhanced neovascularization on islet graft function observed in this study is consistent with recent reports which indicate that islet vascularization is necessary in developing but not adult pancreatic islets in which the primary role of blood vessels has been suggested to be facilitating rapid and adequate delivery of insulin [44–46]. It is noteworthy that there is abundant omental tissue to accommodate high transplant volumes of encapsulated islets in large animal and human studies.…”

Section: Discussionsupporting

confidence: 91%

Long-Term Function of Islets Encapsulated in a Redesigned Alginate Microcapsule Construct in Omentum Pouches of Immune-Competent Diabetic Rats

Pareta¹,

McQuilling²,

Sittadjody³

et al. 2014

Pancreas

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Objectives Our study aim was to determine encapsulated islet graft viability in an omentum pouch and the effect of FGF-1 released from our redesigned alginate microcapsules on the function of the graft. Methods Isolated rat islets were encapsulated in an inner core made with 1.5% low-viscosity high-mannuronic acid (LVM) alginate followed by an external layer made with 1.25% low-viscosity high-guluronic acid (LVG) alginate with or without FGF-1, in microcapsules measuring 300 – 400 μm in diameter. The two alginate layers were separated by a perm-selective membrane made with 0.1 % Poly-L-Ornithine (PLO), and the inner LVM core was partially chelated using 55 mM sodium citrate for 2 min. Results A marginal mass of encapsulated islet allografts (~2000 islets/kg) in Streptozotocin-diabetic Lewis rats caused significant reduction in blood glucose levels similar to the effect observed with encapsulated islet isografts. Transplantation of allo-islets co-encapsulated with FGF-1 did not result in better glycemic control, but induced greater body weight maintenance in transplant recipients compared to those that received only allo-islets. Histological examination of the retrieved tissue demonstrated morphologically and functionally intact islets in the microcapsules, with no signs of fibrosis. Conclusion We conclude that the omentum is a viable site for encapsulated islet transplantation.

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Section: Discussionsupporting

confidence: 91%

Long-Term Function of Islets Encapsulated in a Redesigned Alginate Microcapsule Construct in Omentum Pouches of Immune-Competent Diabetic Rats

Pareta¹,

McQuilling²,

Sittadjody³

et al. 2014

Pancreas

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“…Islets are highly vascularized by a dense capillary network that is composed of endothelial cells and pericytes (3,4). However, although the role of endothelial cells in b-cell homeostasis has been vastly investigated, the role of pericytes remains largely unknown (4)(5)(6).…”

mentioning

confidence: 99%

Islet Pericytes Are Required for β-Cell Maturity

et al. 2016

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β-Cells rely on the islet microenvironment for their functionality and mass. Pericytes, along with endothelial cells, make up the dense islet capillary network. However, although the role of endothelial cells in supporting β-cell homeostasis has been vastly investigated, the role of pericytes remains largely unknown. Here, we focus on contribution of pericytes to β-cell function. To this end, we used a transgenic mouse system that allows diphtheria toxin-based depletion of pericytes. Our results indicate that islets depleted of their pericytes have reduced insulin content and expression. Additionally, isolated islets displayed impaired glucose-stimulated insulin secretion, accompanied by a reduced expression of genes associated with β-cell function. Importantly, reduced levels of the transcription factors MafA and Pdx1 point to β-cell dedifferentiation in the absence of pericytes. Ex vivo depletion of pericytes in isolated islets resulted in a similar impairment of gene expression, implicating their direct, blood flow-independent role in maintaining β-cell maturity. To conclude, our findings suggest that pericytes are pivotal components of the islet niche, which are required for β-cell maturity and functionality. Abnormalities of islet pericytes, as implicated in type 2 diabetes, may therefore contribute to β-cell dysfunction and disease progression.

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“…The most obvious improvement derived from thinner coatings is a shorter diffusion path for molecules such as oxygen, glucose, and insulin. Increased access to oxygen is achieved, since an islet bearing a thinner coating would be in nearer proximity to a blood vessel (Duvillie, 2013) than an islet with a thicker coating; this would ameliorate the hypoxiainduced islet core death that is often associated with grafts in the intraperitoneal space (Safley et al, 2018).…”

Section: Discussionmentioning

confidence: 99%

Conformal Coating of Stem Cell-Derived Islets for β Cell Replacement in Type 1 Diabetes

et al. 2020

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The scarcity of donors and need for immunosuppression limit pancreatic islet transplantation to a few patients with labile type 1 diabetes. Transplantation of encapsulated stem cell-derived islets (SC islets) might extend the applicability of islet transplantation to a larger cohort of patients. Transplantation of conformal-coated islets into a confined well-vascularized site allows long-term diabetes reversal in fully MHC-mismatched diabetic mice without immunosuppression. Here, we demonstrated that human SC islets reaggregated from cryopreserved cells display glucose-stimulated insulin secretion in vitro. Importantly, we showed that conformally coated SC islets displayed comparable in vitro function with unencapsulated SC islets, with conformal coating permitting physiological insulin secretion. Transplantation of SC islets into the gonadal fat pad of diabetic NOD-scid mice revealed that both unencapsulated and conformal-coated SC islets could reverse diabetes and maintain human-level euglycemia for more than 80 days. Overall, these results provide support for further evaluation of safety and efficacy of conformal-coated SC islets in larger species.

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Vascularization of the Pancreas: An Evolving Role From Embryogenesis to Adulthood

Cited by 9 publications

References 16 publications

Long-Term Function of Islets Encapsulated in a Redesigned Alginate Microcapsule Construct in Omentum Pouches of Immune-Competent Diabetic Rats

Long-Term Function of Islets Encapsulated in a Redesigned Alginate Microcapsule Construct in Omentum Pouches of Immune-Competent Diabetic Rats

Islet Pericytes Are Required for β-Cell Maturity

Conformal Coating of Stem Cell-Derived Islets for β Cell Replacement in Type 1 Diabetes

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