title: Efficacy and Safety of Immuno-Magnetically Sorted Smooth Muscle Progenitor Cells Derived from Human-Induced Pluripotent Stem Cells for Restoring Urethral Sphincter Function.
abstract: Human-induced pluripotent stem cells (hiPSCs)-based cell therapy holds promise for treating stress urinary incontinence (SUI). However, safety concerns, especially tumorgenic potential of residual undifferentiated cells in hiPSC derivatives, are major barriers for its clinical translation. An efficient, fast and clinical-scale strategy for purifying committed cells is also required. Our previous studies demonstrated the regenerative effects of hiPSC-derived smooth muscle progenitor cells (pSMCs) on the injured urethral sphincter in SUI, but the differentiation protocol required fluorescence-activated cell sorting (FACS) which is not practical for autologous clinical applications. In this study, we examined the efficacy and safety of hiPSC-derived pSMC populations sorted by FDA-approved magnetic-activated cell sorting (MACS) using cell-surface marker CD34 for restoring urethral sphincter function. Although the heterogeneity of MACS-sorted pSMCs was higher than that of FACS-sorted pSMCs, the percentage of undifferentiated cells dramatically decreased after directed differentiation in vitro. In vivo studies demonstrated long-term cell integration and no tumor formation of MACS-sorted pSMCs after transplantation. Furthermore, transplantation of MACS-sorted pSMCs into immunodeficient SUI rats was comparable to transplantation with FACS-sorted pSMCs for restoration of the extracellular matrix metabolism and function of the urethral sphincter. In summary, purification of hiPSC derivatives using MACS sorting for CD34 expression represent an efficient approach for production of clinical-scale pSMCs for autologous stem cell therapy for regeneration of smooth muscle tissues. Stem Cells Translational Medicine 2017;6:1158-1167.
authors.affiliation: Department of Obstetrics/Gynecology, Stanford University School of Medicine, California, USA.|Department of Obstetrics/Gynecology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, The People's Republic of China.
authors.forename: Yanhui
authors.initials: Y
authors.lastname: Li
authors.affiliation: Department of Obstetrics/Gynecology, Stanford University School of Medicine, California, USA.|Institute for Stem Cell Biology and Regenerative Medicine, Stanford University, California, USA.
authors.forename: Morgaine
authors.initials: M
authors.lastname: Green
authors.affiliation: Department of Obstetrics/Gynecology, Stanford University School of Medicine, California, USA.
authors.forename: Yan
authors.initials: Y
authors.lastname: Wen
authors.affiliation: Department of Obstetrics/Gynecology, Stanford University School of Medicine, California, USA.
authors.forename: Yi
authors.initials: Y
authors.lastname: Wei
authors.affiliation: Department of Obstetrics/Gynecology, Stanford University School of Medicine, California, USA.|Institute for Stem Cell Biology and Regenerative Medicine, Stanford University, California, USA.
authors.forename: Prachi
authors.initials: P
authors.lastname: Wani
authors.affiliation: Department of Obstetrics/Gynecology, Stanford University School of Medicine, California, USA.|Department of Obstetrics/Gynecology, NanFang Hospital, Southern Medical University, Guangzhou, Guangdong, The People's Republic of China.
authors.forename: Zhe
authors.initials: Z
authors.lastname: Wang
authors.affiliation: Department of Cell Biology & Neuroscience.|Department of Chemistry and Biochemistry, Montana State University, Bozeman, Montana, USA.
authors.forename: Renee
authors.initials: R
authors.lastname: Reijo Pera
authors.affiliation: Department of Obstetrics/Gynecology, Stanford University School of Medicine, California, USA.
authors.forename: Bertha
authors.initials: B
authors.lastname: Chen
mesh_terms: D000818:Animals; D002478:Cells, Cultured; D004549:Elastin / Q000378:metabolism; D005260:Female; D005434:Flow Cytometry; D006801:Humans; D057026:Induced Pluripotent Stem Cells / Q000166:cytology* / Q000378:metabolism / Q000502:physiology; D008875:Middle Aged; D009130:Muscle, Smooth / Q000166:cytology*; D051381:Rats; D014549:Urinary Incontinence / Q000628:therapy*
chemical_list: D004549:Elastin
keywords: Cell transplantation; Elastin; Flow cytometry; Immunomagnetic separation; Induced pluripotent stem cell; Myoblast, smooth muscle; Urinary incontinence, stress