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

Author:

Bharadwaj Shantaram1,Liu Guihua1,Shi Yingai1,Wu Rongpei12,Yang Bin13,He Tongchuan4,Fan Yuxin5,Lu Xinyan6,Zhou Xiaobo7,Liu Hong8,Atala Anthony1,Rohozinski Jan19,Zhang Yuanyuan1

Affiliation:

1. Wake Forest Institute of Regenerative Medicine Wake Forest School of Medicine, Winston-SalemNorth Carolina, USA

2. Department of Urology First Affiliated Hospital of Sun Yat-Sen University, Guangzhou, GuangDong, People's Republic of China

3. Department of Urology Shanghai Tenth People's Hospital Tongji University School of Medicine, Shanghai, People's Republic of China

4. Molecular Oncology Laboratory Department of Surgery The University of Chicago Medical Center, Chicago, Illinois, USA

5. John Welsh Cardiovascular Diagnostic Laboratory at Department of Pediatric Baylor College of Medicine, Houston, Texas, USA

6. Clinical Cytogenetics Laboratory Section of Hematology-Oncology Department of Pediatrics Baylor College of Medicine, Houston, Texas, USA

7. Radiology/Translational Biology Department The Methodist Hospital Research Institute, Houston, Texas, USA

8. Center for Bioengineering and School of Electrical and Computer Engineering University of Oklahoma, Norman, Oklahoma, USA

9. Department of Obstetrics and Gynecology Baylor College of Medicine, Houston, Texas, USA

Abstract

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.

Publisher

Oxford University Press (OUP)

Subject

Cell Biology,Developmental Biology,Molecular Medicine

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