Enhanced Differentiation Capacity and Transplantation Efficacy of Insulin-Producing Cell Clusters from Human iPSCs Using Permeable Nanofibrous Microwell-Arrayed Membrane for Diabetes Treatment

Shim, In Kyong; Lee, Seong Jin; Lee, Yu Na; Kim, Dohui; Goh, Hanse; Youn, Jaeseung; Jang, Jinah; Kim, Dong Sung; Kim, Song Cheol

doi:10.3390/pharmaceutics14020400

Open AccessArticle

Enhanced Differentiation Capacity and Transplantation Efficacy of Insulin-Producing Cell Clusters from Human iPSCs Using Permeable Nanofibrous Microwell-Arrayed Membrane for Diabetes Treatment

by

In Kyong Shim

^1,2,†,

Seong Jin Lee

^3,†,

Yu Na Lee

^1,2,†,

Dohui Kim

³,

Hanse Goh

^1,2,

Jaeseung Youn

³,

Jinah Jang

^3,4,5,6

,

Dong Sung Kim

^3,6,7,* and

Song Cheol Kim

^1,2,8,*

¹

Asan Institute for Life Sciences, Asan Medical Center, University of Ulsan College of Medicine, Seoul 05505, Korea

²

Department of Medical Science, Asan Medical Institute of Convergence Science and Technology (AMIST), Asan Medical Center, University of Ulsan College of Medicine, Seoul 05505, Korea

³

Department of Mechanical Engineering, Pohang University of Science and Technology (POSTECH), 77 Cheongam-ro, Nam-gu, Pohang 37673, Korea

⁴

School of Interdisciplinary Bioscience and Bioengineering, Pohang University of Science and Technology (POSTECH), Cheongam-ro, Nam-gu, Pohang 37673, Korea

⁵

Department of Convergence IT Engineering, Pohang University of Science and Technology (POSTECH), 77 Cheongam-ro, Nam-gu, Pohang 37673, Korea

⁶

Institute for Convergence Research and Education in Advanced Technology, Yonsei University, 50 Yonsei-ro, Seodaemun-gu, Seoul 03722, Korea

⁷

Department of Chemical Engineering, Pohang University of Science and Technology (POSTECH), 77 Cheongam-ro, Nam-gu, Pohang 37673, Korea

⁸

Department of Surgery, Asan Medical Center, University of Ulsan College of Medicine, 88 Olympic-ro 43-gil, Songpa-gu, Seoul 05505, Korea

^*

Authors to whom correspondence should be addressed.

^†

These authors contributed equally to this work.

Pharmaceutics 2022, 14(2), 400; https://doi.org/10.3390/pharmaceutics14020400

Submission received: 9 December 2021 / Revised: 8 February 2022 / Accepted: 9 February 2022 / Published: 12 February 2022

(This article belongs to the Special Issue Electrospun Materials for Biomedical Applications)

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Abstract

Although pancreatic islet transplantation is a potentially curative treatment for insulin-dependent diabetes, a shortage of donor sources, low differentiation capacity, and transplantation efficacy are major hurdles to overcome before becoming a standard therapy. Stem cell-derived insulin-producing cells (IPCs) are a potential approach to overcoming these limitations. To improve the differentiation capacity of the IPCs, cell cluster formation is crucial to mimic the 3D structure of the islet. This study developed a biodegradable polycaprolactone (PCL) electrospun nanofibrous (NF) microwell-arrayed membrane permeable to soluble factors. Based on the numerical analysis and experimental diffusion test, the NF microwell could provide sufficient nutrients, unlike an impermeable PDMS (polydimethylsiloxane) microwell. The IPC clusters in the NF microwells showed higher gene expression of insulin and PDX1 and insulin secretion than the PDMS microwells. The IPC clusters in the NF microwell-arrayed membrane could be directly transplanted. Transplanted IPC clusters in the microwells survived well and expressed PDX1 and insulin. Additionally, human c-peptide was identified in the blood plasma at two months after transplantation of the membranes. The NF microwell-arrayed membrane can be a new platform promoting IPC differentiation capacity and realizing an in situ transplantation technique for diabetic patients.

Keywords: iPSC; insulin-producing cells; diabetes; cell cluster; electrospinning; microwell; nanofibrous membrane

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MDPI and ACS Style

Shim, I.K.; Lee, S.J.; Lee, Y.N.; Kim, D.; Goh, H.; Youn, J.; Jang, J.; Kim, D.S.; Kim, S.C. Enhanced Differentiation Capacity and Transplantation Efficacy of Insulin-Producing Cell Clusters from Human iPSCs Using Permeable Nanofibrous Microwell-Arrayed Membrane for Diabetes Treatment. Pharmaceutics 2022, 14, 400. https://doi.org/10.3390/pharmaceutics14020400

AMA Style

Shim IK, Lee SJ, Lee YN, Kim D, Goh H, Youn J, Jang J, Kim DS, Kim SC. Enhanced Differentiation Capacity and Transplantation Efficacy of Insulin-Producing Cell Clusters from Human iPSCs Using Permeable Nanofibrous Microwell-Arrayed Membrane for Diabetes Treatment. Pharmaceutics. 2022; 14(2):400. https://doi.org/10.3390/pharmaceutics14020400

Chicago/Turabian Style

Shim, In Kyong, Seong Jin Lee, Yu Na Lee, Dohui Kim, Hanse Goh, Jaeseung Youn, Jinah Jang, Dong Sung Kim, and Song Cheol Kim. 2022. "Enhanced Differentiation Capacity and Transplantation Efficacy of Insulin-Producing Cell Clusters from Human iPSCs Using Permeable Nanofibrous Microwell-Arrayed Membrane for Diabetes Treatment" Pharmaceutics 14, no. 2: 400. https://doi.org/10.3390/pharmaceutics14020400

APA Style

Shim, I. K., Lee, S. J., Lee, Y. N., Kim, D., Goh, H., Youn, J., Jang, J., Kim, D. S., & Kim, S. C. (2022). Enhanced Differentiation Capacity and Transplantation Efficacy of Insulin-Producing Cell Clusters from Human iPSCs Using Permeable Nanofibrous Microwell-Arrayed Membrane for Diabetes Treatment. Pharmaceutics, 14(2), 400. https://doi.org/10.3390/pharmaceutics14020400

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Enhanced Differentiation Capacity and Transplantation Efficacy of Insulin-Producing Cell Clusters from Human iPSCs Using Permeable Nanofibrous Microwell-Arrayed Membrane for Diabetes Treatment

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