title: Smooth Muscle Precursor Cells Derived from Human Pluripotent Stem Cells for Treatment of Stress Urinary Incontinence.
abstract: There is great interest in using stem cells (SC) to regenerate a deficient urethral sphincter in patients with urinary incontinence. The smooth muscle component of the sphincter is a significant contributor to sphincter function. However, current translational efforts for sphincter muscle restoration focus only on skeletal muscle regeneration because they rely on adult mesenchymal SC as cell source. These adult SC do not yield sufficient smooth muscle cells (SMCs) for transplantation. We may be able to overcome this limitation by using pluripotent stem cell (PSC) to derive SMCs. Hence, we sought to investigate whether smooth muscle precursor cells (pSMCs) derived from human PSCs can restore urethral function in an animal model generated by surgical urethrolysis and ovariectomy. Rats were divided into four groups: control (no intervention), sham saline (surgery + saline injection), bladder SMC (surgery + human bladder SMC injection), and treatment (surgery + pSMC injection, which includes human embryonic stem cell (hESC) H9-derived pSMC, episomal reprogrammed induced pluripotent stem cells (iPSCs)-derived pSMC, or viral reprogrammed iPSC-derived pSMC). pSMCs (2 × 10(6) cells/rat) were injected periurethrally 3 weeks postsurgery. Leak point pressure (LPP) and baseline external urethral sphincter electromyography were measured 5 weeks postinjection. Both iPSC-derived pSMC treatment groups showed significantly higher LPP compared to the sham saline group, consistent with restoration of urethral sphincter function. While the difference between the H9-derived pSMC treatment and sham saline group was not significant, it did show a trend toward restoration of the LPP to the level of intact controls. Our data indicate that pSMCs derived from human PSCs (hESC and iPSC) can restore sphincter function.
authors.affiliation: 1 Department of OB/GYN, Stanford University School of Medicine , Stanford, California.|2 The Center for Reproductive Medicine, OB/GYN, Nanfang Hospital, Southern Medical University , Guangzhou, Guangdong, People's Republic of China .
authors.forename: Zhe
authors.initials: Z
authors.lastname: Wang
authors.affiliation: 1 Department of OB/GYN, Stanford University School of Medicine , Stanford, California.
authors.forename: Yan
authors.initials: Y
authors.lastname: Wen
authors.affiliation: 1 Department of OB/GYN, Stanford University School of Medicine , Stanford, California.|3 The Department of OB/GYN, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology , Wuhan, People's Republic of China .
authors.forename: Yan Hui
authors.initials: YH
authors.lastname: Li
authors.affiliation: 1 Department of OB/GYN, Stanford University School of Medicine , Stanford, California.
authors.forename: Yi
authors.initials: Y
authors.lastname: Wei
authors.affiliation: 1 Department of OB/GYN, Stanford University School of Medicine , Stanford, California.
authors.forename: Morgaine
authors.initials: M
authors.lastname: Green
authors.affiliation: 1 Department of OB/GYN, Stanford University School of Medicine , Stanford, California.
authors.forename: Prachi
authors.initials: P
authors.lastname: Wani
authors.affiliation: 4 Department of Pathology, Stanford University School of Medicine , Stanford, California.
authors.forename: Pengbo
authors.initials: P
authors.lastname: Zhang
authors.affiliation: 5 Department of Cell Biology and Neurosciences and Department of Chemistry and Biochemistry, Montana State University , Bozeman, Montana.
authors.forename: Renee Reijo
authors.initials: RR
authors.lastname: Pera
authors.affiliation: 1 Department of OB/GYN, Stanford University School of Medicine , Stanford, California.
authors.forename: Bertha
authors.initials: B
authors.lastname: Chen
mesh_terms: D000818:Animals; D002478:Cells, Cultured; D005260:Female; D006801:Humans; D032446:Myoblasts / Q000166:cytology / Q000637:transplantation*; D032389:Myocytes, Smooth Muscle / Q000166:cytology*; D039904:Pluripotent Stem Cells / Q000166:cytology* / Q000637:transplantation; D051381:Rats; D033581:Stem Cell Transplantation; D014550:Urinary Incontinence, Stress / Q000628:therapy*