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  • Title: Mature, adipocyte derived, dedifferentiated fat cells can differentiate into smooth muscle-like cells and contribute to bladder tissue regeneration.
    Author: Sakuma T, Matsumoto T, Kano K, Fukuda N, Obinata D, Yamaguchi K, Yoshida T, Takahashi S, Mugishima H.
    Journal: J Urol; 2009 Jul; 182(1):355-65. PubMed ID: 19457498.
    Abstract:
    PURPOSE: We recently reported that mature, adipocyte derived, dedifferentiated fat cells show high proliferative activity and multilineage differentiation potential. In the current study we investigated whether such cells could differentiate into a smooth muscle cell lineage and contribute to bladder tissue regeneration in a mouse bladder injury model. MATERIALS AND METHODS: Human adipocyte derived dedifferentiated fat cells were cultured for 1 week under conditions favorable for smooth muscle cell differentiation and immunostained for alpha-smooth muscle actin. The expression of smooth muscle cell marker genes for differentiating dedifferentiated fat cells was measured by real-time reverse transcription-polymerase chain reaction. Green fluorescence protein labeled dedifferentiated fat cells were injected into cryo-injured bladder walls in mice. The ability of the fat cells to regenerate smooth muscle tissue was examined immunohistochemically 14 and 30 days after transplantation. RESULTS: Immunohistochemical analysis revealed that more than 50% of the fat cells were successfully differentiated into alpha-smooth muscle actin positive cells under the optimum culture condition of a medium containing 5% fetal bovine serum and 5 ng/ml transforming growth factor-beta1. Real-time reverse transcription-polymerase chain reaction revealed increased expression of SM22alpha, alpha-smooth muscle actin and smooth muscle-myosin heavy chain in dedifferentiated fat cells during week 1 of differentiation culture. Cells expressing alpha-smooth muscle actin plus green fluorescence protein were observed at the bladder wall injection sites in mice 14 and 30 days after transplantation. Alpha-smooth muscle actin positive areas in injured bladder tissue in mice with fat cell injection were significantly larger than those in saline injected control mice. CONCLUSIONS: These findings suggest that dedifferentiated fat cells can differentiate into smooth muscle cell lineages and contribute to the regeneration of bladder smooth muscle tissue.
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