Excellent effect of three-dimensional culture condition on pancreatic islets

Hou, Yan; Song, Chao; Xie, Wan; Wei, Zheng; Huang, R.P.; Liu, Wei; Zhang, Zeng Ling; Shi, Yu

doi:10.1016/j.diabres.2009.07.010

Cited by 18 publications

(15 citation statements)

References 27 publications

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“…An explanation to such an observation could be derived by the fact that, while in the direct co-cultures the islets maintained their classical roundish morphology remaining in suspension, in the indirect and mixed co-cultures the islets tended to assume a more elongated shape and to adhere to the Transwell that separated them from the hMSC. Several studies have underlined the importance of maintaining the correct islet structure in order to ensure their functionality, by preserving their phenotype and secretory properties, the islets have to remain in suspension and not to adhere to a substrate (28,32).…”

Section: Discussionmentioning

confidence: 99%

Protective Effect of Human Mesenchymal Stem Cells on the Survival of Pancreatic Islets

Fumagalli

Monfrini

Donzelli

et al. 2020

IJSC

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Background and Objectives: Transplantation of pancreatic islets is an intriguing new therapeutic option to face the worldwide spread problem of Type-I diabetes. Currently, its clinical use is limited by several problems, mainly based on the high number of islets required to restore normoglycaemia and by the low survival of the transplanted tissue. A promising attempt to overcome the limits to such an approach was represented by the use of Mesenchymal Stem Cells (MSC). Despite the encouraging results obtained with murine-derived MSC, little is still known about their protective mechanisms. The aim of the present study was to verify the effectiveness, (besides murine MSC), of clinically relevant human-derived MSC (hMSC) on protecting pancreatic islets, thus also shedding light on the putative differences between MSC of different origin. Methods and Results: Threefold kinds of co-cultures were therefore in vitro set up (direct, indirect and mixed), to analyze the hMSC effect on pancreatic islet survival and function and to study the putative mechanisms involved. Although in a different way with respect to murine MSC, also human derived cells demonstrated to be effective on protecting pancreatic islet survival. This effect could be due to the release of some trophic factors, such as VEGF and Il-6, and by the reduction of inflammatory cytokine TNF-α. Conclusions: Therefore, hMSC confirmed their great clinical potential to improve the feasibility of pancreatic islet transplantation therapy against diabetes.

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Section: Discussionmentioning

confidence: 99%

Protective Effect of Human Mesenchymal Stem Cells on the Survival of Pancreatic Islets

Fumagalli

Monfrini

Donzelli

et al. 2020

IJSC

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“…MSCs, simply added to the culture, can grow in adhesion to floating pancreatic islets, thus preserving both the tridimensional structure of pancreatic islets (and, therefore, their properties), and the correct culture conditions of MSCs, a basic requisite for maintaining their potential. It is important to maintain pancreatic islets in suspension since, when adherent to a substrate, they lose their particular phenotype and secretion properties [28]–[30]. The validity of this kind of culture has already been demonstrated by Duprez et al [31], but only for a short period of culture.…”

Section: Discussionmentioning

confidence: 99%

A Double Mechanism for the Mesenchymal Stem Cells' Positive Effect on Pancreatic Islets

et al. 2014

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The clinical usability of pancreatic islet transplantation for the treatment of type I diabetes, despite some encouraging results, is currently hampered by the short lifespan of the transplanted tissue. In vivo studies have demonstrated that co-transplantation of Mesenchymal Stem Cells (MSCs) with transplanted pancreatic islets is more effective with respect to pancreatic islets alone in ensuring glycemia control in diabetic rats, but the molecular mechanisms of this action are still unclear.The aim of this study was to elucidate the molecular mechanisms of the positive effect of MSCs on pancreatic islet functionality by setting up direct, indirect and mixed co-cultures.MSCs were both able to prolong the survival of pancreatic islets, and to directly differentiate into an “insulin-releasing” phenotype. Two distinct mechanisms mediated these effects: i) the survival increase was observed in pancreatic islets indirectly co-cultured with MSCs, probably mediated by the trophic factors released by MSCs; ii) MSCs in direct contact with pancreatic islets started to express Pdx1, a pivotal gene of insulin production, and then differentiated into insulin releasing cells. These results demonstrate that MSCs may be useful for potentiating pancreatic islets' functionality and feasibility.

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“…Another study using islets cultured on PGA scaffolds confirmed the importance of the 3D environment over injection of islets alone, which were precultured in 2D, showing a twofold reduction in blood glucose levels (257 mg/dL vs. 536 mg/dL) in nude mice. 125 Other studies have also shown that islets encapsulated in synthetic hydrogels are capable of reversing hyperglycemia in nude mice, while unencapsulated cells are not. 121,126 For example, islets encapsulated in a saccharide-peptide hydrogel or in collagen-alginate microbeads and transplanted into nude mice reversed hyperglycemia (blood glucose < 300 mg/dL) for up to 4 weeks, while those grown in suspension culture prior to implantation could not.…”

Section: Preclinical Advancementsmentioning

confidence: 99%

Tissue Engineering Approaches to Cell-Based Type 1 Diabetes Therapy

Amer

Mahoney

Bryant

2014

Tissue Engineering Part B: Reviews

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Type 1 diabetes mellitus is an autoimmune disease resulting from the destruction of insulin-producing pancreatic b-cells. Cell-based therapies, involving the transplantation of functional b-cells into diabetic patients, have been explored as a potential long-term treatment for this condition; however, success is limited. A tissue engineering approach of culturing insulin-producing cells with extracellular matrix (ECM) molecules in threedimensional (3D) constructs has the potential to enhance the efficacy of cell-based therapies for diabetes. When cultured in 3D environments, insulin-producing cells are often more viable and secrete more insulin than those in two dimensions. The addition of ECM molecules to the culture environments, depending on the specific type of molecule, can further enhance the viability and insulin secretion. This review addresses the different cell sources that can be utilized as b-cell replacements, the essential ECM molecules for the survival of these cells, and the 3D culture techniques that have been used to benefit cell function.

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Excellent effect of three-dimensional culture condition on pancreatic islets

Cited by 18 publications

References 27 publications

Protective Effect of Human Mesenchymal Stem Cells on the Survival of Pancreatic Islets

Protective Effect of Human Mesenchymal Stem Cells on the Survival of Pancreatic Islets

A Double Mechanism for the Mesenchymal Stem Cells' Positive Effect on Pancreatic Islets

Tissue Engineering Approaches to Cell-Based Type 1 Diabetes Therapy

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