Culturing Free-Floating and Fibrin-Embedded Islets with Endothelial Cells: Effects on Insulin Secretion and Apoptosis

Dubiel, Evan A.; Lakey, Jonathan R. T.; Lamb, Morgan; Vermette, Patrick

doi:10.1007/s12195-014-0332-0

Cited by 5 publications

(7 citation statements)

References 42 publications

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“…When compared with islets maintained in TCPS plates, islets in decellularized pancreata responded to glucose and secreted more insulin (Figure a). However, comparing islets cultured in TCPS plates with those in 3D scaffolds, such as in decellularized pancreata, is difficult because the diffusional barrier is potentially affecting the GSIS response in 3D matrices (Dubiel, Lakey, Lamb, & Vermette, ). Islets or β cells cultured with ECM molecules showed improved survival and GSIS, by activating NF‐κB signalling and integrin matrix interactions (Hammar et al, ; Kuehn et al, ; Nagata et al, ; Riopel, Stuart, & Wang, ; Yap et al, ).…”

Section: Resultsmentioning

confidence: 99%

Decellularized pancreas as a native extracellular matrix scaffold for pancreatic islet seeding and culture

Damodaran

Vermette

2018

J Tissue Eng Regen Med

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Diabetes mellitus involves the loss of function and/or absolute numbers of insulin-producing β cells in pancreatic islets. Islet transplantation is currently being investigated as a potential cure, and advances in tissue engineering methods can be used to improve pancreatic islets survival and functionality. Transplanted islets experience anoikis, hypoxia, and inflammation-mediated immune response, leading to early damage and subsequent failure of the graft. Recent development in tissue engineering enables the use of decellularized organs as scaffolds for cell therapies. Decellularized pancreas could be a suitable scaffold as it can retain the native extracellular matrix and vasculature. In this study, mouse pancreata were decellularized by perfusion using 0.5% sodium dodecyl sulfate. Different characterizations revealed that the resulting matrix was free of cells and retained part of the pancreas extracellular matrix including the vasculature and its internal elastic basal lamina, the ducts with their basal membrane, and the glycosaminoglycan and collagen structures. Islets were infused into the ductal system of decellularized pancreata, and glucose-stimulated insulin secretion results confirmed their functionality after 48 hr. Also, recellularizing the decellularized pancreas with green fluorescent protein-tagged INS-1 cells and culturing the system over 120 days confirmed the biocompatibility and non-toxic nature of the scaffold. Green fluorescent protein-tagged INS-1 cells formed pseudoislets that were, over time, budding out of the decellularized pancreata. Decellularized pancreatic scaffolds seeded with endocrine pancreatic tissue could be a potential bioengineered organ for transplantation.

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Section: Resultsmentioning

confidence: 99%

Decellularized pancreas as a native extracellular matrix scaffold for pancreatic islet seeding and culture

Damodaran

Vermette

2018

J Tissue Eng Regen Med

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“…This initial boost in the insulin secretion profile has been reported previously by Dubiel et al, who cocultured porcine islets on a monolayer of porcine liver microvascular endothelial cells. 36 They showed that the stimulated insulin secretion improved for 2 days but not for more than 7 days. Similar to Dubiel et al, we cultured the islets in islet culture medium, which might not optimally support the function of the support cells.…”

Section: Discussionmentioning

confidence: 99%

“…The observation that control islets sprout in fibrin gel is in line with previous reports. 9,36,41,43 To our knowledge, no studies have monitored sprouting of control islets in Matrigel. The improved performance in the sprouting capacity of uncoated islets in fibrin compared to Matrigel could be explained by either the difference in matrix composition or stiffness, shown to influence sprout formation of mature endothelial cells both in vitro 42,[44][45][46][47] and in vivo, 33 or the expression of a specific set of fibrinolytic enzymes in intraislet endothelial cells, specifically enabling successful remodeling of the fibrin matrix.…”

Section: Discussionmentioning

confidence: 99%

Coculturing Human Islets with Proangiogenic Support Cells to Improve Islet Revascularization at the Subcutaneous Transplantation Site

Buitinga

Portalska

Cornelissen

et al. 2016

Tissue Engineering Part A

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While subcutaneous tissue has been proposed as a clinically relevant site for pancreatic islet transplantation, a major issue of concern remains, which is its poor vascular state. In an effort to overcome this limitation, we present an efficient and reproducible method to form human composite islets (CIs) with proangiogenic cell types in a controlled manner using nonadherent agarose microwell templates. In this study, we assessed the three-dimensional structure, function, and angiogenic potential of human CIs with human mesenchymal stromal cells (hMSCs), with or without human umbilical vein endothelial cells (HUVECs), and preconditioned hMSCs (PC-hMSCs) in EGM-2 under shear stress. Distinct cellular rearrangements could be observed in CIs, but islet functionality was maintained. In vitro angiogenesis assays found significantly enhanced sprout formation in case of CIs. In particular, the number of sprouts emanating from CIs with PC-hMSCs was significantly increased compared to other conditions. Subsequent in vivo assessment confirmed the proangiogenic potential of CIs. However, in contrast to our in vitro angiogenesis assays, CIs with hMSCs and HUVECs exhibited a higher in vivo angiogenic potential compared to control islets or islets combined with hMSCs or PC-hMSCs. These findings highlight the importance and necessity of verifying in vitro studies with in vivo models to reliably predict, in this case, revascularization outcomes. Regardless, we demonstrate here the therapeutic potential of CIs with proangiogenic support cells to enhance islet revascularization at a clinically relevant, although poorly vascularized, transplantation site.

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“…For example, immobilization of fibronectin, fibrinogen and fibrin on polymer surfaces enhanced the proliferation of smooth muscle cells . Also, embedding pancreatic islets and endothelial cells in fibrin showed increased insulin secretion and preservation of islet integrity . Culturing young porcine islets in fibrin exhibited the protective nature of fibrin towards hydrogen peroxide …”

Section: Rationale For Using Ecm‐based Productsmentioning

confidence: 99%

“…117 Also, embedding pancreatic islets and endothelial cells in fibrin showed increased insulin secretion and preservation of islet integrity. 118 Culturing young porcine islets in fibrin exhibited the protective nature of fibrin towards hydrogen peroxide. 119 In addition to whole ECM proteins, functional peptides derived from the ECM can influence cell behaviors.…”

Section: Chemicals Used For Decellularizationmentioning

confidence: 99%

Tissue and organ decellularization in regenerative medicine

Damodaran

Vermette

2018

Biotechnology Progress

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The advancement and improvement in decellularization methods can be attributed to the increasing demand for tissues and organs for transplantation. Decellularized tissues and organs, which are free of cells and genetic materials while retaining the complex ultrastructure of the extracellular matrix (ECM), can serve as scaffolds to subsequently embed cells for transplantation. They have the potential to mimic the native physiology of the targeted anatomic site. ECM from different tissues and organs harvested from various sources have been applied. Many techniques are currently involved in the decellularization process, which come along with their own advantages and disadvantages. This review focuses on recent developments in decellularization methods, the importance and nature of detergents used for decellularization, as well as on the role of the ECM either as merely a physical support or as a scaffold in retaining and providing cues for cell survival, differentiation and homeostasis. In addition, application, status, and perspectives on commercialization of bioproducts derived from decellularized tissues and organs are addressed. © 2018 American Institute of Chemical Engineers Biotechnol. Prog., 34:1494–1505, 2018

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Culturing Free-Floating and Fibrin-Embedded Islets with Endothelial Cells: Effects on Insulin Secretion and Apoptosis

Cited by 5 publications

References 42 publications

Decellularized pancreas as a native extracellular matrix scaffold for pancreatic islet seeding and culture

Decellularized pancreas as a native extracellular matrix scaffold for pancreatic islet seeding and culture

Coculturing Human Islets with Proangiogenic Support Cells to Improve Islet Revascularization at the Subcutaneous Transplantation Site

Tissue and organ decellularization in regenerative medicine

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