title: Skeletal myogenic differentiation of urine-derived stem cells and angiogenesis using microbeads loaded with growth factors.
abstract: To provide site-specific delivery and targeted release of growth factors to implanted urine-derived stem cells (USCs), we prepared microbeads of alginate containing growth factors. The growth factors included VEGF, IGF-1, FGF-1, PDGF, HGF and NGF. Radiolabeled growth factors were loaded separately and used to access the in vitro release from the microbeads with a gamma counter over 4 weeks. In vitro endothelial differentiation of USCs by the released VEGF from the microbeads in a separate experiment confirmed that the released growth factors from the microbeads were bioactive. USCs and microbeads were mixed with the collagen gel type 1 (2 mg/ml) and used for in vivo studies through subcutaneous injection into nude mice. Four weeks after subcutaneous injection, we found that grafted cell survival was improved and more cells expressed myogenic and endothelial cell transcripts and markers compared to controls. More vessel formation and innervations were observed in USCs combined with six growth factors cocktail incorporated in microbeads compared to controls. In conclusion, a combination of growth factors released locally from the alginate microbeads induced USCs to differentiate into a myogenic lineage, enhanced revascularization and innervation, and stimulated resident cell growth in vivo. This approach could potentially be used for cell therapy in the treatment of stress urinary incontinence.
authors.affiliation: Wake Forest Institute for Regenerative Medicine, Wake Forest School of Medicine, Winston-Salem, NC 27157, USA.
authors.forename: Guihua
authors.initials: G
authors.lastname: Liu
authors.forename: Rajesh A
authors.initials: RA
authors.lastname: Pareta
authors.forename: Rongpei
authors.initials: R
authors.lastname: Wu
authors.forename: Yingai
authors.initials: Y
authors.lastname: Shi
authors.forename: Xiaobo
authors.initials: X
authors.lastname: Zhou
authors.forename: Hong
authors.initials: H
authors.lastname: Liu
authors.forename: Chunhua
authors.initials: C
authors.lastname: Deng
authors.forename: Xiangzhou
authors.initials: X
authors.lastname: Sun
authors.forename: Anthony
authors.initials: A
authors.lastname: Atala
authors.forename: Emmanuel C
authors.initials: EC
authors.lastname: Opara
authors.forename: Yuanyuan
authors.initials: Y
authors.lastname: Zhang
mesh_terms: D000328:Adult; D002454:Cell Differentiation / Q000187:drug effects; D006801:Humans; D036341:Intercellular Signaling Peptides and Proteins / Q000494:pharmacology*; D008297:Male; D008863:Microspheres; D018485:Muscle Fibers, Skeletal / Q000166:cytology* / Q000187:drug effects / Q000502:physiology*; D053769:Nanocapsules; D018919:Neovascularization, Physiologic / Q000187:drug effects / Q000502:physiology*; D013234:Stem Cells / Q000166:cytology* / Q000187:drug effects / Q000502:physiology*; D014556:Urine / Q000166:cytology*
chemical_list: D036341:Intercellular Signaling Peptides and Proteins; D053769:Nanocapsules