Self-organized insulin-producing β-cells differentiated from human omentum-derived stem cells and their in vivo therapeutic potential
- 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.
- All Author(s)
- Ji Hoon Jeong
; Ki Nam Park
; Joo Hyun Kim
; KyungMu Noh
; Sung Sik Hur
; Yunhye Kim
; Moonju Hong
; Jun Chul Chung
; Jae Hong Park
; Jongsoon Lee
; Young-Ik Son
; Ju Hun Lee
; Sang-Heon Kim
; Yongsung Hwang
- Issued Date
- 2023
- Type
- Article
- Keyword
- Cell adhesion; Cell-to-cell interaction; Fibroblast growth factor 2; Insulin-producing cells; Pancreatic β-cells; Stem cell differentiation; Streptozotocin-induced diabetic models
- Publisher
- 한국생체재료학회
Korean Society for Biomaterials
- ISSN
- 2055-7124
; 1226-4601
- Citation Title
- Biomaterials research
- Citation Volume
- 27
- Citation Number
- 1
- Citation Start Page
- 82
- Citation End Page
- 82
- Language(ISO)
- eng
- DOI
- 10.1186/s40824-023-00419-1
- URI
- http://schca-ir.schmc.ac.kr/handle/2022.oak/3346
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