정지훈 (순천향대학교/순천향의생명연구원)

한빛사논문

조회435

정지훈Ji Hoon Jeong

순천향대학교/순천향의생명연구원

Biomater. Res., Aug 29 2023, 27 (1) 82 | https://doi.org/10.1186/s40824-023-00419-1 Self-organized insulin-producing β-cells differentiated from human omentum-derived stem cells and their in vivo therapeutic potential.

Ji Hoon Jeong^1,2†, Ki Nam Park^3†, Joo Hyun Kim^1,4, KyungMu Noh^1,2, Sung Sik Hur¹, Yunhye Kim^1,2, Moonju Hong¹, Jun Chul Chung⁵, Jae Hong Park⁴, Jongsoon Lee^1,2, Young‑Ik Son⁶, Ju Hun Lee^7*, Sang‑Heon Kim^8,9* and Yongsung Hwang^1,2*

¹Soonchunhyang Institute of Medi-Bio Science (SIMS), Soonchunhyang University, Cheonan, Chungnam‑Do 31151, Republic of Korea.

²Department of Integrated Biomedical Science, Soonchunhyang University, Asan, Chungnam‑Do 31538, Republic of Korea.

³Department of Otorhinolaryngology‑Head and Neck Surgery, Soonchunhyang University Bucheon Hospital, Soonchunhyang University College of Medicine, Bucheon 14584, Republic of Korea.

⁴Department of Otorhinolaryngology‑Head and Neck Surgery, Soonchunhyang University Cheonan Hospital, Cheonan 31151, Republic of Korea.

⁵Department of Surgery, Soonchunhyang University Bucheon Hospital, Bucheon 14584, Republic of Korea.

⁶Department of Otorhinolaryngology‑Head and Neck Surgery, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul 06351, Republic of Korea.

⁷Department of Bionano Engineering, Center for Bionano Intelligence Education and Research, Hanyang University, Ansan 15588, Republic of Korea.

⁸Center for Biomaterials, Biomedical Research Institute, Korea Institute of Science and Technology, Seoul 02792, Republic of Korea.

⁹Department of Bio‑Med Engineering, KIST School, Korea University of Science and Technology, Seoul 02792, Republic of Korea.

†Ji Hoon Jeong and Ki Nam Park contributed equally to this study

*Correspondence: Ju Hun Lee, Sang‑Heon Kim, Yongsung Hwang

Abstract

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. 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. 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. 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.

논문정보

형식Research article
게재일2023년 08월 (BRIC 등록일 2023-09-12)
연구진국내 연구진
분야 의약학 > 재생의학

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