title: Transplantation of bone marrow-derived mesenchymal stem cells expressing elastin alleviates pelvic floor dysfunction.
abstract: BACKGROUND
  Pelvic floor dysfunction (PFD) is a group of clinical conditions including stress urinary incontinence (SUI) and pelvic organ prolapse (POP). The abnormality of collagen and elastin metabolism in pelvic connective tissues is implicated in SUI and POP.
  
  
  METHODS
  To reconstitute the connective tissues with normal distribution of collagen and elastin, we transduced elastin to bone marrow-derived mesenchymal stem cells (BMSC). Elastin-expressing BMSCs were then differentiated to fibroblasts using bFGF, which produced collagen and elastin. To achieve the sustained release of bFGF, we formulated bFGF in poly (lactic-co-glycolic acid) (PLGA) nanoparticles (NP).
  
  
  RESULTS
  In an in vitro cell culture system of 7 days, when no additional bFGF was administrated, the initial PLGA-loaded bFGF NP induced prolonged production of collagen and elastin from elastin-expressing BMSCs. In vivo, co-injection of PLGA-loaded bFGF NP and elastin-expressing BMSCs into the PFD rats significantly improved the outcome of urodynamic tests. Together, these results provided an efficient model of connective tissue engineering using BMSC and injectable PLGA-loaded growth factors.
  
  
  CONCLUSIONS
  Our results provided the first instance of a multidisciplinary approach, combining both stem cell and nanoparticle technologies, for the treatment of PFD.
authors.affiliation: Department of Obstetrics and Gynecology, Xinhua Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, 200092, China.
authors.forename: Minfei
authors.initials: M
authors.lastname: Jin
authors.affiliation: Department of Obstetrics and Gynecology, Xinhua Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, 200092, China.
authors.forename: Ying
authors.initials: Y
authors.lastname: Chen
authors.affiliation: Department of Obstetrics and Gynecology, Xinhua Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, 200092, China.
authors.forename: Yun
authors.initials: Y
authors.lastname: Zhou
authors.affiliation: Department of Obstetrics and Gynecology, Xinhua Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, 200092, China.
authors.forename: Yan
authors.initials: Y
authors.lastname: Mei
authors.affiliation: Department of Orthopaedic Surgery, Shanghai Jiaotong University Affiliated Sixth People's Hospital, Shanghai, 200233, China.
authors.forename: Wei
authors.initials: W
authors.lastname: Liu
authors.affiliation: Department of Orthopaedic Surgery, Shanghai Jiaotong University Affiliated Sixth People's Hospital, Shanghai, 200233, China.
authors.forename: Chenhao
authors.initials: C
authors.lastname: Pan
authors.affiliation: Department of Obstetrics and Gynecology, Xinhua Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, 200092, China. huaxiaolin_sh@163.com.
authors.forename: Xiaolin
authors.initials: X
authors.lastname: Hua
mesh_terms: D000818:Animals; D001854:Bone Marrow Cells / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D002454:Cell Differentiation / Q000187:drug effects; D003094:Collagen / Q000235:genetics* / Q000378:metabolism; D004195:Disease Models, Animal; D004339:Drug Compounding; D004549:Elastin / Q000235:genetics* / Q000378:metabolism; D005260:Female; D016222:Fibroblast Growth Factor 2 / Q000737:chemistry / Q000494:pharmacology*; D005347:Fibroblasts / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D015870:Gene Expression; D019344:Lactic Acid / Q000737:chemistry; D045164:Mesenchymal Stem Cell Transplantation; D059630:Mesenchymal Stem Cells / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D053758:Nanoparticles / Q000737:chemistry; D056887:Pelvic Organ Prolapse / Q000235:genetics / Q000378:metabolism / Q000473:pathology / Q000628:therapy*; D011100:Polyglycolic Acid / Q000737:chemistry; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D051381:Rats; D017207:Rats, Sprague-Dawley; D014161:Transduction, Genetic; D014549:Urinary Incontinence / Q000235:genetics / Q000378:metabolism / Q000473:pathology / Q000628:therapy*
chemical_list: D016222:Fibroblast Growth Factor 2; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011100:Polyglycolic Acid; D019344:Lactic Acid; D003094:Collagen; D004549:Elastin
keywords: Basic fibroblast growth factor; Bone marrow-derived mesenchymal stem cells; Pelvic floor dysfunction; Stress urinary incontinence