Improved efficacy and in vivo cellular properties of human embryonic stem cell derivative in a preclinical model of bladder pain syndrome

• Published in: Scientific reports 2017-08, Vol.7 (1), p.8872-16, Article 8872
• Main Authors: Kim, Aram, Yu, Hwan Yeul, Lim, Jisun, Ryu, Chae-Min, Kim, Yong Hwan, Heo, Jinbeom, Han, Ju-Young, Lee, Seungun, Bae, Yoon Sung, Kim, Jae Young, Bae, Dong-Jun, Kim, Sang-Yeob, Noh, Byeong-Joo, Hong, Ki-Sung, Han, Ji-Yeon, Lee, Sang Wook, Song, Miho, Chung, Hyung-Min, Kim, Jun Ki, Shin, Dong-Myung, Choo, Myung-Soo
• Format: Article
• Language: English
• Subjects: 13/100; 13/51; 14/19; 38; 38/77; 59/5; 631/532/2063; 631/532/2074; Animal models; Apoptosis; Bladder; Bone marrow; Cystitis; Denudation; Fibrosis; Graft rejection; Humanities and Social Sciences; Hypersensitivity; Injection; Mesenchyme; Metastases; multidisciplinary; Pain; Pelvis; Science; Science (multidisciplinary); Stem cell transplantation; Stem cells; Tumorigenesis; Urinary bladder; Urothelium
• ISSN: 2045-2322; 2045-2322
• DOI: 10.1038/s41598-017-09330-x

Interstitial cystitis/bladder pain syndrome (IC/BPS) is an intractable disease characterized by severe pelvic pain and urinary frequency. Mesenchymal stem cell (MSC) therapy is a promising approach to treat incurable IC/BPS. Here, we show greater therapeutic efficacy of human embryonic stem cell (hESC)-derived multipotent stem cells (M-MSCs) than adult bone-marrow (BM)-derived counterparts for treating IC/BPS and also monitor long-term safety and in vivo properties of transplanted M-MSCs in living animals. Controlled hESC differentiation and isolation procedures resulted in pure M-MSCs displaying typical MSC behavior. In a hydrochloric-acid instillation-induced IC/BPS animal model, a single local injection of M-MSCs ameliorated bladder symptoms of IC/BPS with superior efficacy compared to BM-derived MSCs in ameliorating bladder voiding function and histological injuries including urothelium denudation, mast-cell infiltration, tissue fibrosis, apoptosis, and visceral hypersensitivity. Little adverse outcomes such as abnormal growth, tumorigenesis, or immune-mediated transplant rejection were observed over 12-months post-injection. Intravital confocal fluorescence imaging tracked the persistence of the transplanted cells over 6-months in living animals. The infused M-MSCs differentiated into multiple cell types and gradually integrated into vascular-like structures. The present study provides the first evidence for improved therapeutic efficacy, long-term safety, and in vivo distribution and cellular properties of hESC derivatives in preclinical models of IC/BPS.