Intravital imaging and single cell transcriptomic analysis for engraftment of mesenchymal stem cells in an animal model of interstitial cystitis/bladder pain syndrome

Hwan Yeul Yu; Seungun Lee; Hyein Ju; Youngkyu Kim; Jung-Hyun Shin; HongDuck Yun; Chae-Min Ryu; Jinbeom Heo; Jisun Lim; Sujin Song; Sanghwa Lee; Ki-Sung Hong; Hyung-Min Chung; Jun Ki Kim; Myung-Soo Choo; Dong-Myung Shin

doi:10.1016/j.biomaterials.2021.121277

Intravital imaging and single cell transcriptomic analysis for engraftment of mesenchymal stem cells in an animal model of interstitial cystitis/bladder pain syndrome

Biomaterials. 2022 Jan:280:121277. doi: 10.1016/j.biomaterials.2021.121277. Epub 2021 Nov 27.

Authors

Hwan Yeul Yu¹, Seungun Lee², Hyein Ju², Youngkyu Kim³, Jung-Hyun Shin⁴, HongDuck Yun², Chae-Min Ryu⁵, Jinbeom Heo², Jisun Lim², Sujin Song², Sanghwa Lee³, Ki-Sung Hong⁶, Hyung-Min Chung⁶, Jun Ki Kim³, Myung-Soo Choo⁷, Dong-Myung Shin⁸

Affiliations

¹ Department of Urology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, South Korea; Department of Biomedical Sciences, Asan Medical Center, University of Ulsan College of Medicine, Seoul, South Korea; ToolGen Inc., Seoul, South Korea.
² Department of Biomedical Sciences, Asan Medical Center, University of Ulsan College of Medicine, Seoul, South Korea; Department of Physiology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, South Korea.
³ Biomedical Engineering Research Center, Asan Institute for Life Sciences, Asan Medical Center, Seoul, South Korea; Department of Convergence Medicine, University of Ulsan, College of Medicine, Seoul, South Korea.
⁴ Department of Urology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, South Korea.
⁵ Department of Urology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, South Korea; Department of Biomedical Sciences, Asan Medical Center, University of Ulsan College of Medicine, Seoul, South Korea.
⁶ Department of Stem Cell Biology, School of Medicine, Konkuk University, Seoul, South Korea; Mirae Cell Bio Co., Ltd., Seoul, South Korea.
⁷ Department of Urology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, South Korea. Electronic address: mschoo@amc.seoul.kr.
⁸ Department of Biomedical Sciences, Asan Medical Center, University of Ulsan College of Medicine, Seoul, South Korea; Department of Physiology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, South Korea. Electronic address: d0shin03@amc.seoul.kr.

PMID: 34861510
DOI: 10.1016/j.biomaterials.2021.121277

Abstract

Mesenchymal stem cell (MSC) therapy is a promising treatment for various intractable disorders including interstitial cystitis/bladder pain syndrome (IC/BPS). However, an analysis of fundamental characteristics driving in vivo behaviors of transplanted cells has not been performed, causing debates about rational use and efficacy of MSC therapy. Here, we implemented two-photon intravital imaging and single cell transcriptome analysis to evaluate the in vivo behaviors of engrafted multipotent MSCs (M-MSCs) derived from human embryonic stem cells (hESCs) in an acute IC/BPS animal model. Two-photon imaging analysis was performed to visualize the dynamic association between engrafted M-MSCs and bladder vasculature within live animals until 28 days after transplantation, demonstrating the progressive integration of transplanted M-MSCs into a perivascular-like structure. Single cell transcriptome analysis was performed in highly purified engrafted cells after a dual MACS-FACS sorting procedure and revealed expression changes in various pathways relating to pericyte cell adhesion and cellular stress. Particularly, FOS and cyclin dependent kinase-1 (CDK1) played a key role in modulating the migration, engraftment, and anti-inflammatory functions of M-MSCs, which determined their in vivo therapeutic potency. Collectively, this approach provides an overview of engrafted M-MSC behavior in vivo, which will advance our understanding of MSC therapeutic applications, efficacy, and safety.

Keywords: FOS; Interstitial cystitis/bladder pain syndrome; Intravital imaging; Mesenchymal stem cell; Single cell analysis.

Publication types

Research Support, Non-U.S. Gov't
Review

MeSH terms

Animals
Cystitis, Interstitial* / therapy
Disease Models, Animal
Intravital Microscopy
Mesenchymal Stem Cell Transplantation* / methods
Mesenchymal Stem Cells*
Transcriptome