Multipotential differentiation of human urine-derived stem cells: Potential for therapeutic applications in urology

Authors

  • Shantaram Bharadwaj,

    1. Wake Forest Institute of Regenerative Medicine, Wake Forest School of Medicine, Winston-Salem, USA
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  • Guihua Liu,

    1. Wake Forest Institute of Regenerative Medicine, Wake Forest School of Medicine, Winston-Salem, USA
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  • Yingai Shi,

    1. Wake Forest Institute of Regenerative Medicine, Wake Forest School of Medicine, Winston-Salem, USA
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  • Rongpei Wu,

    1. Wake Forest Institute of Regenerative Medicine, Wake Forest School of Medicine, Winston-Salem, USA
    2. Department of Urology, First Affiliated Hospital of Sun Yat-Sen University, GuangDong, People's Republic of China
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  • Bin Yang,

    1. Wake Forest Institute of Regenerative Medicine, Wake Forest School of Medicine, Winston-Salem, USA
    2. Department of Urology Shanghai Tenth People's Hospital, Tongji University School of Medicine, Shanghai, People's Republic of China
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  • Tongchuan He,

    1. Molecular Oncology Laboratory Department of Surgery, The University of Chicago Medical Center, Chicago, Illinois, USA
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  • Yuxin Fan,

    1. John Welsh Cardiovascular Diagnostic Laboratory at Department of Pediatric, Baylor College of Medicine, Houston, Texas, USA
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  • Xinyan Lu,

    1. Clinical Cytogenetics Laboratory Section of Hematology-Oncology Department of Pediatrics, Baylor College of Medicine, Houston, Texas, USA
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  • Xiaobo Zhou,

    1. Radiology/Translational Biology Department, The Methodist Hospital Research Institute, Houston, Texas, USA
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  • Hong Liu,

    1. Center for Bioengineering and School of Electrical and Computer Engineering, University of Oklahoma, Norman, Oklahoma, USA
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  • Anthony Atala,

    1. Wake Forest Institute of Regenerative Medicine, Wake Forest School of Medicine, Winston-Salem, USA
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  • Jan Rohozinski,

    1. Wake Forest Institute of Regenerative Medicine, Wake Forest School of Medicine, Winston-Salem, USA
    2. Department of Obstetrics and Gynecology, Baylor College of Medicine, Houston, Texas, USA
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  • Yuanyuan Zhang

    Corresponding author
    1. Wake Forest Institute of Regenerative Medicine, Wake Forest School of Medicine, Winston-Salem, USA
    • Wake Forest Institute for Regenerative Medicine, Wake Forest School of Medicine, Medical Center Boulevard, Winston-Salem, NC 27157, USA. E-mail: yzhang@wakehealth.edu Telephone: 336-713-1189; Fax: 336-713-7290

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  • Author contributions: S.B. and G.L.: collection and assembly of data, data analysis and interpretation, and manuscript writing; Y.S., R.W., B.Y., T.H., and Y.F.: collection and assembly of data and data analysis and interpretation; X.L., X.Z., H.L., and J.R.: data analysis and interpretation; A.A.: financial support, administrative support, and provision of study material; Y.Z.: conception and design, data analysis and interpretation, and manuscript writing; S.B., G.L., Y.S., R.W., B.Y., T.H, Y.F., X.L., X.Z., H.L., J.R., A.A., and Y.Z.: final approval of manuscript. S.B. and G.L. contributed equally to this article.

Abstract

We sought to biologically characterize and identify a subpopulation of urine-derived stem cells (USCs) with the capacity for multipotent differentiation. We demonstrated that single USCs can expand to a large population with 60–70 population doublings. Nine of 15 individual USC clones expressed detectable levels of telomerase and have long telomeres. These cells expressed pericyte and mesenchymal stem cell markers. Upon induction with appropriate media in vitro, USCs differentiated into bladder-associated cell types, including functional urothelial and smooth muscle cell lineages. When the differentiated USCs were seeded onto a scaffold and subcutaneously implanted into nude mice, multilayered tissue-like structures formed consisting of urothelium and smooth muscle. Additionally, USCs were able to differentiate into endothelial, osteogenic, chondrogenic, adipogenic, skeletal myogenic, and neurogenic lineages but did not form teratomas during the 1-month study despite telomerase activity. USCs may be useful in cell-based therapies and tissue engineering applications, including urogenital reconstruction. STEM Cells 2013;

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