Abstract
The field of regenerative medicine continues to make substantial advancements in therapeutic strategies addressing urologic diseases. Tissue engineering borrows principles from the fields of cell biology, materials science, transplantation and engineering in an effort to repair or replace damaged tissues. This review is intended to provide a current overview of the use of stem cells and tissue engineering technologies specifically in the treatment of genitourinary diseases. Current themes in the field include the use of adult stem cells seeded onto biocompatible resorbable matrices for implantation as tissue substitutes, which is conducive to host tissue in-growth. Injection therapy of adult stem cells for organ rehabilitation is also making strong headway toward the restoration of organ structure and function. With new data describing the molecular mechanisms for differentiation, work has begun on targeting tissues for regeneration by genetic modification methods. Promising laboratory discoveries portend the emergence of a new class of clinical therapies for regenerative medicine applications in the genitourinary tract.
Similar content being viewed by others
Log in or create a free account to read this content
Gain free access to this article, as well as selected content from this journal and more on nature.com
or
Abbreviations
- hESC:
-
human embryonic stem cells
- NIH:
-
National Institutes of Health
- SIS:
-
small intestine submucosa
- SUI:
-
stress urinary incontinence
- TE:
-
tissue engineering
References
Langer R, Vacanti JP 1993 Tissue engineering. Science 260: 920–926
Vacanti CA 2006 The history of tissue engineering. J Cell Mol Med 10: 569–576
Vacanti JP 2007 Tissue engineering: a 20 year personal perspective [editorial]. Tissue Eng 13: 231–232
Atala A, Nyberg LM 2000 Tissue engineering. World J Urol 18: 1
Mikos AG, Herring SW, Ochareon P, Elisseeff J, Lu HH, Kandel R, Schoen FJ, Toner M, Mooney D, Atala A, Van Dyke ME, Kaplan D, Vunjak-Novakovic G 2006 Engineering complex tissues. Tissue Eng 12: 3307–3339
Atala A 2006 Recent developments in tissue engineering and regenerative medicine. Curr Opin Pediatr 18: 167–171
Park H, Cannizzaro C, Vunjak-Navokavic G, Langer R, Vacanti CA, Farokhzad OC 2007 Nanofabrication and microfabrication of functional materials for tissue engineering. Tissue Eng 13: 1867–1877
Brehmer B, Rohrmann D, Becker C, Rau G, Jakse G 2007 Different types of scaffolds for reconstruction of the urinary tract by tissue engineering. Urol Int 78: 23–29
Sievert KD, Amend B, Stenzl A 2007 Tissue engineering for the lower urinary tract: a review of a state of the art approach. Eur Urol 52: 1580–1589
Chen F, Yoo JJ, Atala A 1999 Acellular collagen matrix as a possible “off the shelf” biomaterial for urethral repair. Urology 54: 407–410
Atala A 1999 Future perspective in reconstructive surgery using tissue engineering. Urol Clin North Am 26: 157–165
Atala A, Freeman MR, Vacanti JP, Shepard J, Retik AB 1993 Implantation in vivo and retrieval of artificial structures consisting of rabbit and human urothelium and human bladder muscle. J Urol 150: 608–612
Godbey WT, Atala A 2002 In vitro systems for tissue engineering. Ann N Y Acad Sci 961: 10–26
Dahms SE, Piechota HJ, Dahiya R, Lue TF, Tanagho EA 1998 Composition and biomechanical properties of the bladder acellular matrix graft: comparative analysis in rat, pig and human. Br J Urol 82: 411–419
Piechota HJ, Dahms SE, Nunes LS, Dahiya R, Lue TF, Tanagho EA 1998 In vitro functional properties of the rat bladder regenerated by the bladder acellular matrix graft. J Urol 159: 1717–1724
Atala A 2004 Tissue engineering for the replacement of organ function in the genitourinary system. Am J Transplant 4: 58–73
David R, Groebner M, Franz WM 2005 Magnetic cell sorting purification of differentiated embryonic stem cells stably expressing truncated human CD4 as surface marker. Stem Cells 23: 477–482
Hynes RO 1992 Integrins: versatility, modulation, and signaling in cell adhesion. Cell 69: 11–25
Deuel TF 1997 Growth factors. In: Lanza RP, Langer R, Chick WL (eds) Principles of Tissue Engineering. Academic Press, New York, pp 133–149
Kim BS, Mooney DJ 1998 Development of biocompatible synthetic extracellular matrices for tissue engineering. Trends Biotechnol 16: 224–230
Keller G 2005 Embryonic stem cell differentiation: emergence of a new era in biology and medicine. Genes Dev 19: 1129–1155
Becker C, Gerhard J 2007 Stem cells for regeneration of urological structures. Eur Urol 51: 1217–1228
Thomson JA, Itskovitz-Eldor J, Shapiro SS, Waknitz MA, Swiergiel JJ, Marshall VS, Jones JM 1998 Embryonic stem cell lines derived from human blastocysts. Science 282: 1145–1147
Reubinoff BE, Pera MF, Fong CY, Trounson A, Bongso A 2000 Embryonic stem cell lines from human blastocysts: somatic differentiation in vitro. Nat Biotechnol 18: 399–404
Itskovitz-Eldor J, Schuldiner M, Karsenti D, Eden A, Yanuka O, Amit M, Soreq H, Benvenisty N 2000 Differentiation of human embryonic stem cells into embryoid bodies comprising the three embryonic germ layers. Mol Med 6: 88–95
Kennedy D 2003 Stem cells: still here, still waiting. Science 300: 865
Marchant J 2006 Human eggs supply ‘ethical' stem cells. Nature 441: 1038
Atala A, Koh CJ 2004 Tissue engineering applications of therapeutic cloning. Annu Rev Biomed Eng 6: 27–40
Vrana KE, Hipp JD, Goss AM, McCool BA, Riddle DR, Walker SJ, Wettstein PJ, Studer LP, Tabar V, Cunnuff K, Chapman K, Vilner L, West MD, Grant KA, Cibelli JB 2003 Nonhuman primate parthenogenetic stem cells. Proc Natl Acad Sci USA 100: 11911–11916
Peterson BE, Bowen WC, Patrene Mars WM, Sullivan AK, Murase N, Boggs SS, Greenberger JS, Goff JP 1999 Bone marrow as a potential source of hepatic oval cells. Science 284: 1168–1170
Fierabracci A, Caione P, Di Giovine M, Zavaglia D, Bottazzo GF 2007 Identification and characterization of adult stem/progenitor cells in the human bladder (bladder spheroids): perspectives in application in pediatric surgery. Pediatr Surg Int 23: 837–839
Chung SY, Koh CJ 2007 Fetal tissues. In: Atala A, Lanza R, Nerem R, Thomson JA (eds) Principles of Regenerative Medicine. Academic Press, Burlington, MA, pp 968–977
De Coppi P, Bartsch G Jr, Siddiqui MM, Xu T, Santos CC, Perin L, Mostoslavsky G, Serre AC, Snyder EY, Yoo JJ, Furth ME, Soker S, Atala A 2007 Isolation of amniotic stem cells lines with potential for therapy. Nat Biotechnol 25: 100–106
In't Anker PS, Scherjon SA, Kleijburg-van der Keur C, Noort WA, Claas FH, Willemze R, Fibbe WE, Kanhai HH 2003 Amniotic fluid as a novel source of mesenchymal stem cells for therapeutic transplantation. Blood 102: 1548–1549
Tsai MS, Hwang SM, Tsai YL, Cheng FC, Lee JL, Chang YJ 2006 Clonal amniotic fluid-derived stem cells express characteristics of both mesenchymal and neural stem cells. Biol Reprod 74: 545–551
Smith TG III, Gettman M, Lindberg G, Napper C, Pearle MS, Cadeddu JA 2002 Ureteral replacement using porcine small intestine submucosa in a porcine model. Urology 60: 931–934
Dahms SE, Piechota HJ, Nunes L, Dahiya R, Lue TF, Tanagho EA 1997 Free ureteral replacement in rats: regeneration of ureteral wall components in the acellular matrix graft. Urology 50: 818–825
Osman Y, Shokeir A, Gabr M, El-Tabey N, Mohsen T, El-Baz M 2004 Canine ureteral replacement with long acellular matrix tube: is it clinically applicable?. J Urol 172: 1151–1154
El-Hakim A, Marcovish R, Chiu K-Y, Lee BR, Smith AD 2005 Ureteral segmental replacement revisited. J Endourol 19: 1069–1074
Matsunuma H, Kagami H, Narita Y, Hata K-I, Ono Y, Ohshima S, Ueda M 2006 Constructing a tissue engineered ureter using decellularized matrix with cultured uroepithelial cells and bone marrow-derived mononuclear cells. Tissue Eng 12: 509–518
Lakshmanan Y, Fromberger D, Hearhart JD, Gearhart JP 2005 Human embryoid body-derived stem cells in co-culture with bladder smooth muscle and urothelium. Urology 65: 821–826
Frimberger D, Morales N, Shamblott M, Gearhart JD, Gearhart JP, Lakshmanan Y 2005 Human embryoid body-derived stem cells in bladder regeneration using rodent model. Urology 65: 827–832
Obara T, Matsura S, Narita S, Satoh S, Tsuchiya N, Habuchi T 2006 Bladder acellular matrix grafting regenerates urinary bladder in the spinal cord injury rat. Urology 68: 892–897
Kanematsu A, Yamamoto S, Noguchi T, Ozeki M, Tabata Y, Ogawa O 2003 Bladder regeneration by bladder acellular matrix combined with sustained release of exogenous growth factor. J Urol 170: 1633–1638
Atala A, Bauer SB, Soker S, Yoo JJ, Retik AB 2006 Tissue-engineered autologous bladders for patients needing cystoplasty. Lancet 367: 1241–1246
Korossis S, Bolland F, Ingham E, Fisher J, Kearney J, Southgate J 2006 Tissue engineering of the urinary bladder: considering structure-function relationships and the role of mechanotransduction. Tissue Eng 12: 635–644
Sodian R, Lemke T, Fritsche C, Hoerstrup SP, Fu P, Potapov EV, Hausmann H, Hetzer R 2002 Tissue-engineering bioreactors: a new combined cell seeding and perfusion system for vascular tissue engineering. Tissue Eng 8: 863–870
Kim B-S, Nikolovski J, Bonadio J, Mooney DJ 1999 Cyclic mechanical strain regulates development of engineered smooth muscle tissue. Nat Biotechnol 17: 979–983
Taylor RA, Cowin PA, Cunha GR, Pera M, Trounson AO, Pederson J, Risbridger GP 2006 Formation of human prostate tissue from embryonic stem cells. Nat Methods 3: 179–181
Aboseif S, El-Sakka A, Young P, Cunha G 1999 Mesenchymal reprogramming of adult human epithelial differentiation. Differentiation 65: 113–118
O'connor KC 1999 Three-dimensional cultures of prostatic cells: tissue models for the development of novel anti-cancer therapies. Pharm Res 16: 486–493
Han B, Grassl ED, Barocas VH, Coad JE, Bischof JC 2005 A cryoinjury model using engineered tissue equivalents for cryosurgical applications. Ann Biomed Eng 33: 972–982
Fu Q, Deng C-L 2006 Ten year experience with composite bladder mucosa-skin grafts in hypospadias repair. Urology 67: 1274–1277
De Filippo RE, Yoo JJ, Atala A 2002 Urethral replacement using cell seeded tubularized collagen matrices. J Urol 168: 1789–1792; discussion 1792–1793.
Fu Q, Deng CL, Liu W, Cao YL 2007 Urethral replacement using epidermal cell-seeded tubular acellular bladder collagen matrix. BJU Int 99: 1162–1165
Bach AD, Bannasch H, Galla TJ, Bittner KM, Stark GB 2001 Fibrin glue as matrix for cultured autologous urothelial cells in urethral reconstruction. Tissue Eng 7: 45–54
El-Kassaby AW, Retik AB, You JJ, Atala A 2003 Urethral stricture repair with an off-the-shelf collagen matrix. J Urol 169: 170–173
Atala A, Guzman L, Retik AB 1999 A novel inert collagen matrix for hypospadias repair. J Urol 162: 1148–1151
Nygaard I, Thom DH, Calhoun E 2007 Urinary incontinence in women. In: Litwin MS, Saigal CS (eds) Urologic Diseases in America. NIH/NIDDK Publication No. 07-5512, Bethesda, MD, pp 157–191.
Stothers L, Thom DH, Calhoun E 2007 Urinary incontinence in men. In: Litwin MS, Saigal CS (eds) Urologic Diseases in America. NIH/NIDDK Publication No. 07-5512, Bethesda, MD, pp 193–222
Strasser H, Marksteiner R, Margreiter E, Pinggera GM, Mitterberger M, Frauscher F, Ulmer H, Fussenegger M, Kofler K, Bartsch G 2007 Autologous myoblasts and fibroblasts versus collagen for treatment of stress urinary incontinence in women: a randomized controlled trial. Lancet 369: 2179–2186
Mitterberger M, Pinggera GM, Marksteiner R, Margreiter E, Fussenegger M, Frauscher F, Ulmer H, Hering S, Bartsch G, Strasser H 2008 Adult stem cell therapy of female stress urinary incontinence. Eur Urol 53: 169–175
Strasser H, Marksteiner R, Margreiter E, Mitterberger M, Pinggera GM, Frauscher F, Fussenegger M, Kofler K, Bartsch G 2007 Transurethral ultrasonography-guided injection of adult autologous stem cell versus transurethral endoscopic injection of collagen in treatment of urinary incontinence. World J Urol 25: 385–392
Lecoeur C, Swieb S, Zini L, Riviere C, Combrisson H, Gherardi R, Abbou C, Yiou R 2007 Intraurethral transfer of satellite cells by myofiber implants results in the formation of innervated myotubes exerting tonic contractions. J Urol 178: 332–337
Cannon TW, Sweeney DD, Conway DA, Kamo I, Yoshimura N, Sacks M, Chancellor MB 2005 A tissue-engineered suburethral sling in an animal model of stress urinary incontinence. BJU Int 96: 664–669
Wessells H, Joyce GF, Wise M, Wilt TJ 2007 Erectile dysfunction and Peyronie's disease. In: Litwin MS, Saigal CS (eds) Urologic Diseases in America. Bethesda, MD, NIH/NIDDK Publication No. 07-5512, pp 483–530.
Gelbard MK, Hayden B 1991 Expanding contractures of the tunica albuginea due to Peyronies's disease with temporalis fascia free grafts. J Urol 145: 772–776
Leungwattanakij S, Tiewthanom V, Hellstrom WJ 2003 Evaluation of corporal fibrosis in cadaveric pericardium and vein grafts for tunica albuginea substitution in rats. Asian J Androl 5: 295–299
Seftel AD, Oates RD, Goldstein I 1992 Use of polytetraflouroethylene tube graft as a circumferential neotunica during replacement of a penile prosthesis. J Urol 148: 1531–1533
Joo KJ, Kim B-S, Han J-H, Kim C-J, Kwon C-H, Park H-J 2006 Porcine vesical acellular matrix graft of tunica albuginea for penile reconstruction. Asian J Androl 8: 543–548
Breyer BN, Brant WO, Garcia MM, Bella AJ, Lue TF 2007 Complications of porcine small intestine submucosa graft for Peyronie's Disease. J Urol 177: 589–591
Rosen RC, Cappelleri JC, Smith MD, Lipsky J, Pena BM 1999 Development and evaluation of an abridged, 5-item version of the International Index of Erectile Function (IIEF-5) as a diagnostic tool for erectile dysfunction. Int J Impot Res 11: 319–326
Falke G, Yoo JJ, Kwon TG, Moreland R, Atala A 2003 Formation of corporal tissue architecture in vivo using human cavernosal muscle and endothelial cells seeded on collagen matrices. Tissue Eng 9: 871–879
Walsh PC 2001 Nerve grafts are rarely necessary and unlikely to improve sexual function in men undergoing anatomic radical prostatectomy. Urology 57: 1020–1024
Kim ED, Nath R, Slawin KM, Kadmin D, Miles BJ, Scardino TS 2001 Bilateral nerve grafting during radical retropubic prostatectomy; extended follow-up. Urology 58: 983–987
Scardino PT, Kim ED 2001 Rationale for and results of nerve grafting during radical prostatectomy. Urology 57: 1016–1019
May F, Vroemen M, Matiasek K, Henke J, Brill T, Lehmer A, Apprich M, Erhardt W, Schoeler S, Paul R, Blesch A, Hartung R, Gansbacher B, Weidner N 2005 Nerve replacement strategies for cavernous nerves. Eur Urol 48: 372–378
Deng W, Bivalacqua TJ, Hellstrom WJ, Kadowitz PJ 2005 Gene and stem cell therapy for erectile dysfunction. Int J Impot Res 17: S57–S63
Song YS, Lee HJ, Park IH, Kim WK, Ku JH, Kim SU 2007 Potential differentiation of human mesenchymal stem cell transplanted in rat corpus cavernosum toward endothelial or smooth muscle cells. Int J Impot Res 19: 378–385
Author information
Authors and Affiliations
Corresponding author
Rights and permissions
About this article
Cite this article
Yamzon, J., Kokorowski, P. & Koh, C. Stem Cells and Tissue Engineering Applications of the Genitourinary Tract. Pediatr Res 63, 472–477 (2008). https://doi.org/10.1203/PDR.0b013e31816a704a
Received:
Accepted:
Issue date:
DOI: https://doi.org/10.1203/PDR.0b013e31816a704a
This article is cited by
-
Novel therapeutic approaches of tissue engineering in male infertility
Cell and Tissue Research (2020)
-
A novel kartogenin-platelet-rich plasma gel enhances chondrogenesis of bone marrow mesenchymal stem cells in vitro and promotes wounded meniscus healing in vivo
Stem Cell Research & Therapy (2019)
-
Biomaterial Scaffolds for Reproductive Tissue Engineering
Annals of Biomedical Engineering (2017)
-
Stem cells: novel players in the treatment of erectile dysfunction
Asian Journal of Andrology (2012)
