한빛사논문
- 조회695
Hwan Yeul Yua,b,h,1, Seungun Leeb,c,1, Hyein Jub,c, Youngkyu Kimd,e, Jung-Hyun Shina, HongDuck Yunb,c, Chae-Min Ryua,b, Jinbeom Heob,c, Jisun Limb,c, Sujin Songa,b, Sanghwa Leed,e, Ki-Sung Hongf,g, Hyung-Min Chungf,g, Jun Ki Kimd,e, Myung-Soo Chooa,*, Dong-Myung Shinb,c,*
aDepartment of Urology, South Korea
bDepartment of Biomedical Sciences, South Korea
cDepartment of Physiology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, South Korea
dBiomedical Engineering Research Center, Asan Institute for Life Sciences, Asan Medical Center, Seoul, South Korea
eDepartment of Convergence Medicine, University of Ulsan, College of Medicine, Seoul, South Korea
fDepartment of Stem Cell Biology, School of Medicine, Konkuk University, Seoul, South Korea
gMirae Cell Bio Co., Ltd., Seoul, South Korea
hToolGen Inc., Seoul, South Korea
1These authors contributed equally to this work.
*Corresponding author.
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 : Intravital imaging, Single cell analysis, Mesenchymal stem cell, FOS, Interstitial cystitis/bladder pain syndrome
논문정보
- Research article
- 2021년 11월 (BRIC 등록일 2021-12-06)
- 국내 연구진
- 의약학 > 분자세포의학
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