Importance of Heparan Sulfate Proteoglycans in Pancreatic Islets and β-Cells

Takahashi, Ikuo

doi:10.3390/ijms232012082

Cited by 1 publication

(1 citation statement)

References 158 publications

(217 reference statements)

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“…In this study, by harnessing FGF2-conjugated MBP with a hydrophobic region and HSPG binding affinity, we engineered a novel cell culture platform that controls the cell-matrix interaction-mediated promotion of β-cell differentiation and function. As previously reported, heparan sulfate (HS) is distributed and concentrated in the intercellular region within human islets of Langerhans [46]. Furthermore, HS is known to strongly affect β-cell proliferation and function as well as regulate the availability of growth factors at active sites [47,48].…”

Section: Discussionmentioning

confidence: 91%

Self-organized insulin-producing β-cells differentiated from human omentum-derived stem cells and their in vivo therapeutic potential

Jeong,

Park,

Kim

et al. 2023

Biomater Res

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Background Human omentum-derived mesenchymal stem cells (hO-MSCs) possess great potential to differentiate into multiple lineages and have self-renewal capacity, allowing them to be utilized as patient-specific cell-based therapeutics. Although the use of various stem cell-derived β-cells has been proposed as a novel approach for treating diabetes mellitus, developing an efficient method to establish highly functional β-cells remains challenging. Methods We aimed to develop a novel cell culture platform that utilizes a fibroblast growth factor 2 (FGF2)-immobilized matrix to regulate the adhesion and differentiation of hO-MSCs into insulin-producing β-cells via cell–matrix/cell–cell interactions. In our study, we evaluated the in vitro differentiation potential of hO-MSCs cultured on an FGF2-immobilized matrix and a round-bottom plate (RBP). Further, the in vivo therapeutic efficacy of the β-cells transplanted into kidney capsules was evaluated using animal models with streptozotocin (STZ)-induced diabetes. Results Our findings demonstrated that cells cultured on an FGF2-immobilized matrix could self-organize into insulin-producing β-cell progenitors, as evident from the upregulation of pancreatic β-cell-specific markers (PDX-1, Insulin, and Glut-2). Moreover, we observed significant upregulation of heparan sulfate proteoglycan, gap junction proteins (Cx36 and Cx43), and cell adhesion molecules (E-cadherin and Ncam1) in cells cultured on the FGF2-immobilized matrix. In addition, in vivo transplantation of differentiated β-cells into animal models of STZ-induced diabetes revealed their survival and engraftment as well as glucose-sensitive production of insulin within the host microenvironment, at over 4 weeks after transplantation. Conclusions Our findings suggest that the FGF2-immobilized matrix can support initial cell adhesion, maturation, and glucose-stimulated insulin secretion within the host microenvironment. Such a cell culture platform can offer novel strategies to obtain functional pancreatic β-cells from patient-specific cell sources, ultimately enabling better treatment for diabetes mellitus. Graphical Abstract

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Section: Discussionmentioning

confidence: 91%