Self-organized insulin-producing β-cells differentiated from human omentum-derived stem cells and their in vivo therapeutic potentialopen access
- Authors
- Jeong, Ji Hoon; Park, Ki Nam; Kim, Joo Hyun; Noh, KyungMu; Hur, Sung Sik; Kim, Yunhye; Hong, Moonju; Chung, Jun Chul; Park, Jae Hong; Lee, Jongsoon; Son, Young-Ik; Lee, Ju Hun; Kim, Sang-Heon; Hwang, Yongsung
- Issue Date
- Aug-2023
- Publisher
- BioMed Central Ltd
- Keywords
- Cell adhesion; Cell-to-cell interaction; Fibroblast growth factor 2; Insulin-producing cells; Pancreatic β-cells; Stem cell differentiation; Streptozotocin-induced diabetic models
- Citation
- Biomaterials Research, v.27, no.1, pp 1 - 18
- Pages
- 18
- Indexed
- SCIE
SCOPUS
KCI
- Journal Title
- Biomaterials Research
- Volume
- 27
- Number
- 1
- Start Page
- 1
- End Page
- 18
- URI
- https://scholarworks.bwise.kr/erica/handle/2021.sw.erica/115124
- DOI
- 10.1186/s40824-023-00419-1
- ISSN
- 1226-4601
2055-7124
- Abstract
- 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: [Figure not available: see fulltext.] © 2023, The Korean Society for Biomaterials.
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