title: Bone Marrow Stem/Progenitor Cells Attenuate the Inflammatory Milieu Following Substitution Urethroplasty.
abstract: Substitution urethroplasty for the treatment of male stricture disease is often accompanied by subsequent tissue fibrosis and secondary stricture formation. Patients with pre-existing morbidities are often at increased risk of urethral stricture recurrence brought upon in-part by delayed vascularization accompanied by overactive inflammatory responses following surgery. Within the context of this study, we demonstrate the functional utility of a cell/scaffold composite graft comprised of human bone marrow-derived mesenchymal stem cells (MSC) combined with CD34+ hematopoietic stem/progenitor cells (HSPC) to modulate inflammation and wound healing in a rodent model of substitution urethroplasty. Composite grafts demonstrated potent anti-inflammatory effects with regards to tissue macrophage and neutrophil density following urethral tissue analyses. This was accompanied by a significant reduction in pro-inflammatory cytokines TNFα and IL-1β and further resulted in an earlier transition to tissue remodeling and maturation with a shift in collagen type III to I. Grafted animals demonstrated a progressive maturation and increase in vessel size compared to control animals. Overall, MSC/CD34+ HSPC composite grafts reduce inflammation, enhance an earlier transition to wound remodeling and maturation concurrently increasing neovascularization in the periurethral tissue. We demonstrate the feasibility and efficacy of a stem cell-seeded synthetic graft in a rodent substitution urethroplasty model.
authors.affiliation: Department of Urology, Northwestern University Feinberg School of Medicine, Chicago, IL USA.
authors.forename: Joceline S
authors.initials: JS
authors.lastname: Liu
authors.affiliation: Division of Pediatric Urology, Ann &Robert H. Lurie Children's Hospital of Chicago, Chicago, IL USA.
authors.forename: Matthew I
authors.initials: MI
authors.lastname: Bury
authors.affiliation: Division of Pediatric Urology, Ann &Robert H. Lurie Children's Hospital of Chicago, Chicago, IL USA.
authors.forename: Natalie J
authors.initials: NJ
authors.lastname: Fuller
authors.affiliation: Division of Pediatric Urology, Ann &Robert H. Lurie Children's Hospital of Chicago, Chicago, IL USA.
authors.forename: Renea M
authors.initials: RM
authors.lastname: Sturm
authors.affiliation: Division of Pediatric Urology, Ann &Robert H. Lurie Children's Hospital of Chicago, Chicago, IL USA.
authors.forename: Nida
authors.initials: N
authors.lastname: Ahmad
authors.affiliation: Department of Urology, Northwestern University Feinberg School of Medicine, Chicago, IL USA.|Division of Pediatric Urology, Ann &Robert H. Lurie Children's Hospital of Chicago, Chicago, IL USA.|Simpson Querrey Institute for BioNanotechnology, Northwestern University, Chicago, IL USA.|Department of Biomedical Engineering, Northwestern University, Chicago, IL USA.|Stanley Manne Children's Research Institute, Chicago, IL USA.
authors.forename: Arun K
authors.initials: AK
authors.lastname: Sharma
mesh_terms: D000818:Animals; D004195:Disease Models, Animal; D006412:Hematopoietic Stem Cells / Q000502:physiology*; D006801:Humans; D007249:Inflammation / Q000517:prevention & control*; D059630:Mesenchymal Stem Cells / Q000502:physiology*; D019651:Plastic Surgery Procedures / Q000009:adverse effects*; D012377:Rodentia; D033581:Stem Cell Transplantation; D013234:Stem Cells / Q000502:physiology*; D016896:Treatment Outcome; D014525:Urethral Stricture / Q000601:surgery*