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Urine-Derived Stem Cells: Biological Characterization and Potential Clinical Applications

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Stem Cells: Current Challenges and New Directions

Part of the book series: Stem Cell Biology and Regenerative Medicine ((STEMCELL))

Abstract

A subpopulation of urine-derived cells, termed urine-derived stem cells (USCs), possess stem cell capabilities, such as self-renewal and multipotential differentiation. These cells can differentiate into mesodermal cell lineages, such as osteocytes, chondrocytes, adipocytes, endothelial cells, and myocytes, including smooth muscle cell differentiation and endodermal lineages (e.g., urothelial cells). These cells maintain high telomerase activity and possess long telomeres; further, they retain a normal karyotype in vitro even after several passages. Importantly, these cells do not form teratomas in vivo. USCs express cell surface markers associated with pericytes and mesenchymal stem cells. These cells can be isolated from regular voided urine from each individual via a noninvasive, simple, and low-cost approach. The USCs isolated from one single urine specimen can generate up to 100 million cells at early passage, sufficient numbers to use for cell-based therapy for tissue repair.

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Abbreviations

3-D:

Three-dimension

ECs:

Endothelial cells

EFM:

Embryonic fibroblast medium

EGF:

Epidermal growth factor

FDA:

Food and Drug Administration

HUVECs:

Human umbilical venous endothelial cells

KSFM:

Keratinocyte serum-free medium

MSC:

Mesenchymal stem cells

PD:

Population doublings

PDGF-rβ:

Platelet-derived growth factor-B and -receptor

RPM:

Revolutions per minute

SIS:

Small intestinal submucosa

SMCs:

Smooth muscle cells

UCs:

Urothelial cells

UPCs:

Urine-derived progenitor cells

USCs:

Urine-derived stem cells

uUSCs:

Stem cells collected from upper urinary tract

VEGF:

Vascular endothelial growth factor

vUSCs:

Stem cells collected from voided urine samples

vWF:

Von Willebrand factor

α-SM actin:

Alpha-smooth muscle actin

References

  1. Zhang Y, McNeill E, Tian H, Soker S, Andersson KE, Yoo JJ, Atala A (2008) Urine derived cells are a potential source for urological tissue reconstruction. J Urol 180:2226–2233

    Article  CAS  PubMed  Google Scholar 

  2. Bodin A, Bharadwaj S, Wu S, Gatenholm P, Atala A, Zhang Y (2010) Tissue-engineered conduit using urine-derived stem cells seeded bacterial cellulose polymer in urinary reconstruction and diversion. Biomaterials 31:8889–8901

    Article  CAS  PubMed  Google Scholar 

  3. Wu S, Liu Y, Bharadwaj S, Atala A, Zhang Y (2011) Human urine-derived stem cells seeded in a modified 3D porous small intestinal submucosa scaffold for urethral tissue engineering. Biomaterials 32:1317–1326

    Article  PubMed  Google Scholar 

  4. Bharadwaj S, Liu G, Shi Y, Markert CD, Andersson KE, Atala A, Zhang Y (2011) Characterization of urine-derived stem cells obtained from upper urinary tract for use in cell-based urological tissue engineering. Tissue Eng Part A 17:2123–2132

    Article  PubMed  Google Scholar 

  5. Bharadwaj S, Wu S, Rohozinski J, Further M, Lan X, Atala A, Zhang Y. (2009) Multipotential differentiation of human urine-derived stem cells. Tissue Engineering and Regenerative Medicine. 6:S293

    Google Scholar 

  6. Zhang YY, Ludwikowski B, Hurst R, Frey P (2001) Expansion and long-term culture of differentiated normal rat urothelial cells in vitro. In Vitro Cell Dev Biol Anim 37:419–429

    Article  CAS  PubMed  Google Scholar 

  7. Meirelles Lda S, Fontes AM, Covas DT, Caplan AI (2009) Mechanisms involved in the therapeutic properties of mesenchymal stem cells. Cytokine Growth Factor Rev 20:419–427

    Article  PubMed  Google Scholar 

  8. Baksh D, Song L, Tuan RS (2004) Adult mesenchymal stem cells: characterization, differentiation, and application in cell and gene therapy. J Cell Mol Med 8:301–316

    Article  CAS  PubMed  Google Scholar 

  9. Beyer Nardi N, da Meirelles Silva L (2006) Mesenchymal stem cells: isolation, in vitro expansion and characterization. Handb Exp Pharmacol 174:249–282

    PubMed  Google Scholar 

  10. Short B, Brouard N, Occhiodoro-Scott T, Ramakrishnan A, Simmons PJ (2003) Mesenchymal stem cells. Arch Med Res 34:565–571

    Article  CAS  PubMed  Google Scholar 

  11. Nombela-Arrieta C, Ritz J, Silberstein LE (2011) The elusive nature and function of mesenchymal stem cells. Nat Rev Mol Cell Biol 12:126–131

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  12. Bharadwaj BW, Wu S, Rohozinski S, Furth J, Atala A, Zhang Y (2009) Multipotential differentiation of human urine-derived stem cells. Tissue Engineering and Regenerative medicine 2nd World Congress. S293

    Google Scholar 

  13. Oberpenning F, Meng J, Yoo JJ, Atala A (1999) De novo reconstitution of a functional mammalian urinary bladder by tissue engineering. Nat Biotechnol 17:149–155

    Article  CAS  PubMed  Google Scholar 

  14. Liu Y, Wu S, Bharadwaj S, Atala A, Zhang Y (2010) Urethral tissue engineering with urine derived stem cells seeded on small intestine submucosa. Biomaterials

    Google Scholar 

  15. Czaja W, Krystynowicz A, Bielecki S, Brown RM Jr (2006) Microbial cellulose–the natural power to heal wounds. Biomaterials 27:145–151

    Article  CAS  PubMed  Google Scholar 

  16. Helenius G, Backdahl H, Bodin A, Nannmark U, Gatenholm P, Risberg B (2006) In vivo biocompatibility of bacterial cellulose. J Biomed Mater Res A 76:431–438

    Article  PubMed  Google Scholar 

  17. Backdahl H, Helenius G, Bodin A, Nannmark U, Johansson BR, Risberg B, Gatenholm P (2006) Mechanical properties of bacterial cellulose and interactions with smooth muscle cells. Biomaterials 27:2141–2149

    Article  PubMed  Google Scholar 

  18. Zhang Y (2008) Bladder reconstruction by tissue engineering–with or without cells? J Urol 180:10–11

    Article  PubMed  Google Scholar 

  19. Zhang Y, Frimberger D, Cheng EY, Lin HK, Kropp BP (2006) Challenges in a larger bladder replacement with cell-seeded and unseeded small intestinal submucosa grafts in a subtotal cystectomy model. BJU Int 98:1100–1105

    Article  PubMed  Google Scholar 

  20. Zhang Y, Kropp BP, Lin HK, Cowan R, Cheng EY (2004) Bladder regeneration with cell-seeded small intestinal submucosa. Tissue Eng 10:181–187

    Article  PubMed  Google Scholar 

  21. Zhang Y, Kropp BP, Moore P, Cowan R, Furness PD 3rd, Kolligian ME, Frey P, Cheng EY (2000) Coculture of bladder urothelial and smooth muscle cells on small intestinal submucosa: potential applications for tissue engineering technology. J Urol 164:928–934, discussion 934-925

    Google Scholar 

  22. Zhang Y, Lin HK, Frimberger D, Epstein RB, Kropp BP (2005) Growth of bone marrow stromal cells on small intestinal submucosa: an alternative cell source for tissue engineered bladder. BJU Int 96:1120–1125

    Article  CAS  PubMed  Google Scholar 

  23. Kropp BP, Zhang Y, Lin HK, Cowan R, Cheng EY (2002) Tissue engineering bladder regeneration with cell seeded small intestinal submucosa (SIS). J Urol Annual meeting, AUA program Abstracts. 59

    Google Scholar 

  24. Zhang YS, Li HZ, Zhang RQ, Wang P (2005) Preliminary research on preparation of porcine bladder acellular matrix graft for tissue engineering applications. Zhonghua Yi Xue Za Zhi 85:2724–2727

    PubMed  Google Scholar 

  25. Liu Y, Bharadwaj S, Lee SJ, Atala A, Zhang Y (2009) Optimization of a natural collagen scaffold to aid cell-matrix penetration for urologic tissue engineering. Biomaterials 30:3865–3873

    Article  CAS  PubMed  Google Scholar 

  26. Youssif M, Shiina H, Urakami S, Gleason C, Nunes L, Igawa M, Enokida H, Tanagho EA, Dahiya R (2005) Effect of vascular endothelial growth factor on regeneration of bladder acellular matrix graft: histologic and functional evaluation. Urology 66:201–207

    Article  PubMed  Google Scholar 

  27. Tian H, Bharadwaj S, Liu Y, Ma H, Ma PX, Atala A, Zhang Y (2010) Myogenic differentiation of human bone marrow mesenchymal stem cells on a 3D nano fibrous scaffold for bladder tissue engineering. Biomaterials 31:870–877

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  28. Deasy BM, Feduska JM, Payne TR, Li Y, Ambrosio F, Huard J (2009) Effect of VEGF on the regenerative capacity of muscle stem cells in dystrophic skeletal muscle. Mol Ther 17:1788–1798

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  29. Bryan BA, Walshe TE, Mitchell DC, Havumaki JS, Saint-Geniez M, Maharaj AS, Maldonado AE, D'Amore PA (2008) Coordinated vascular endothelial growth factor expression and signaling during skeletal myogenic differentiation. Mol Biol Cell 19:994–1006

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  30. Wu S, Wang Z, Bharadwaj S, Hodges SJ, Atala A, Zhang Y (2011) Implantation of autologous urine derived stem cells expressing vascular endothelial growth factor for potential use in genitourinary reconstruction. J Urol 186:640–647

    Article  CAS  PubMed  Google Scholar 

  31. Tian H, Bharadwaj S, Liu Y, Ma PX, Atala A, Zhang Y (2010) Differentiation of human bone marrow mesenchymal stem cells into bladder cells: potential for urological tissue engineering. Tissue Eng Part A 16:1769–1779

    Article  CAS  PubMed Central  PubMed  Google Scholar 

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Acknowledgments

The authors would like to thank Dr. Jenifer Olson for her editorial assistance.

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Authors and Affiliations

  1. Wake Forest Institute for Regenerative Medicine, Wake Forest University School of Medicine, Medical Center Boulevard, Winston Salem, NC, 27157, USA

    Guihua Liu, Chunhua Deng & Yuanyuan Zhang

Authors
  1. Guihua Liu
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  2. Chunhua Deng
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  3. Yuanyuan Zhang
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Corresponding author

Correspondence to Yuanyuan Zhang .

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Editors and Affiliations

  1. Regenerative Medicine Program, Ottawa Hospital Research Institute Sprott Centre for Stem Cell Research, Ottawa, Ontario, Canada

    Kursad Turksen

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Liu, G., Deng, C., Zhang, Y. (2013). Urine-Derived Stem Cells: Biological Characterization and Potential Clinical Applications. In: Turksen, K. (eds) Stem Cells: Current Challenges and New Directions. Stem Cell Biology and Regenerative Medicine. Humana Press, New York, NY. https://doi.org/10.1007/978-1-4614-8066-2_2

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