title: Differentiation of human bone marrow mesenchymal stem cells into bladder cells: potential for urological tissue engineering.
abstract: Bone marrow mesenchymal stem cells (BMSCs) are capable of differentiating into multiple cell types, providing an alternative cell source for cell-based therapy and tissue engineering. Simultaneous differentiation of human BMSCs into smooth muscle cells (SMCs) and urothelium would be beneficial for clinical applications in bladder regeneration for patients with bladder exstrophy or cancer who need cystoplasty. We investigated the ability of human BMSCs to differentiate toward both SMCs and urothelium with cocultured or conditioned media and analyzed growth factors from a coculture system. After being cocultured with urothelium or cultured using urothelium-derived conditioned medium, human BMSCs expressed urothelium-specific genes and proteins: uroplakin-Ia, cytokeratin-7, and cytokeratin-13. When cocultured with SMCs or cultured in SMC-conditioned medium, human BMSCs expressed SMC-specific genes and proteins: desmin and myosin. Several growth factors (hepatocyte growth factor, platelet-derived growth factor-homodimer polypeptide of B chain (BB), transforming growth factor-beta1, and vascular endothelial growth factor) were detected in the SMC cocultured media and in the urothelium cocultured media (epidermal growth factor, platelet-derived growth factor-BB, transforming growth factor-beta1, and vascular endothelial growth factor). BMSC-scaffold constructs significantly improved cell contractility after myogenic differentiation. In vivo-grafted cells displayed significant matrix infiltration and expressed SMC-specific markers in the nanofibrous poly-l-lactic acid scaffolds. In conclusion, smooth muscle- and urothelium-like cells derived from human BMSCs provide an alternative cell source for potential use in bladder tissue engineering.
authors.affiliation: Wake Forest Institute for Regenerative Medicine, Wake Forest University School of Medicine, Winston-Salem, NC 27157, USA.
authors.forename: Hong
authors.initials: H
authors.lastname: Tian
authors.forename: Shantaram
authors.initials: S
authors.lastname: Bharadwaj
authors.forename: Yan
authors.initials: Y
authors.lastname: Liu
authors.forename: Peter X
authors.initials: PX
authors.lastname: Ma
authors.forename: Anthony
authors.initials: A
authors.lastname: Atala
authors.forename: Yuanyuan
authors.initials: Y
authors.lastname: Zhang
mesh_terms: D000293:Adolescent; D000328:Adult; D001854:Bone Marrow Cells / Q000166:cytology*; D002454:Cell Differentiation / Q000187:drug effects; D019070:Cell Lineage / Q000187:drug effects; D002648:Child; D018920:Coculture Techniques; D017077:Culture Media, Conditioned / Q000494:pharmacology; D005786:Gene Expression Regulation / Q000187:drug effects; D006801:Humans; D059630:Mesenchymal Stem Cells / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism; D009119:Muscle Contraction / Q000187:drug effects; D024510:Muscle Development / Q000187:drug effects; D032389:Myocytes, Smooth Muscle / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D009928:Organ Specificity / Q000187:drug effects; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D023822:Tissue Engineering / Q000379:methods*; D001743:Urinary Bladder / Q000166:cytology*; D019459:Urothelium / Q000166:cytology / Q000187:drug effects; D055815:Young Adult
chemical_list: D017077:Culture Media, Conditioned; D012333:RNA, Messenger