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Tissue engineering, stem cells, cloning, and parthenogenesis: new paradigms for therapy

Journal of Experimental & Clinical Assisted Reproduction volume 1, Article number: 3 (2004) Cite this article

Abstract

Background

Patients suffering from diseased and injured organs may be treated with transplanted organs. However, there is a severe shortage of donor organs which is worsening yearly due to the aging population. Scientists in the field of tissue engineering apply the principles of cell transplantation, materials science, and bioengineering to construct biological substitutes that will restore and maintain normal function in diseased and injured tissues. Both therapeutic cloning (nucleus from a donor cell is transferred into an enucleated oocyte), and parthenogenesis (oocyte is activated and stimulated to divide), permit extraction of pluripotent embryonic stem cells, and offer a potentially limitless source of cells for tissue engineering applications. The stem cell field is also advancing rapidly, opening new options for therapy. The present article reviews recent progress in tissue engineering and describes applications of these new technologies that may offer novel therapies for patients with end-stage organ failure.

References

  1. Cilento BG, Freeman MR, Schneck FX, Retik AB, Atala A: Phenotypic and cytogenetic characterization of human bladder urothelia expanded in vitro. J Urol. 1994, 152: 665-670.

    Article  CAS  PubMed  Google Scholar 

  2. Scriven SD, Booth C, Thomas DF, Trejdosiewicz LK, Southgate J: Reconstitution of human urothelium from monolayer cultures. J Urol. 1997, 158: 1147-1152. 10.1097/00005392-199709000-00115.

    Article  PubMed  CAS  Google Scholar 

  3. Liebert M, Hubbel A, Chung M, Wedemeyer G, Lomax MI, Hegeman A, Yuan TY, Brozovich M, Wheelock MJ, Grossman HB: Expression of mal is associated with urothelial differentiation in vitro: identification by differential display reverse-transcriptase polymerase chain reaction. Differentiation. 1997, 61: 177-185. 10.1046/j.1432-0436.1997.6130177.x.

    Article  PubMed  CAS  Google Scholar 

  4. Puthenveettil JA, Burger MS, Reznikoff CA: Replicative senescence in human uroepithelial cells. Adv Exp Med Biol. 1999, 462: 83-91.

    Article  CAS  PubMed  Google Scholar 

  5. Freeman MR, Yoo JJ, Raab G, Soker S, Adam RM, Schneck FX, Renshaw AA, Klagsbrun M, Atala A: Heparin-binding EGF-like growth factor is an autocrine growth factor for human urothelial cells and is synthesized by epithelial and smooth muscle cells in the human bladder. J Clin Invest. 1997, 99: 1028-1036.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  6. Nguyen HT, Park JM, Peters CA, Adam RM, Orsola A, Atala A, Freeman MR: Cell-specific activation of the HB-EGF and ErbB1 genes by stretch in primary human bladder cells. In Vitro Cell Dev Biol Anim. 1999, 35: 371-375.

    Article  CAS  PubMed  Google Scholar 

  7. Liebert M, Wedemeyer G, Abruzzo LV, Kunkel SL, Hammerberg C, Cooper KD, Grossman HB: Stimulated urothelial cells produce cytokines and express an activated cell surface antigenic phenotype. Semin Urol. 1991, 9: 124-130.

    PubMed  CAS  Google Scholar 

  8. Harriss DR: Smooth muscle cell culture: a new approach to the study of human detrusor physiology and pathophysiology. Br J Urol. 1995, 75 Suppl 1: 18-26.

    PubMed  CAS  Google Scholar 

  9. Solomon LZ, Jennings AM, Sharpe P, Cooper AJ, Malone PS: Effects of short-chain fatty acids on primary urothelial cells in culture: implications for intravesical use in enterocystoplasties. J Lab Clin Med. 1998, 132: 279-283. 10.1016/S0022-2143(98)90040-3.

    Article  PubMed  CAS  Google Scholar 

  10. Lobban ED, Smith BA, Hall GD, Harnden P, Roberts P, Selby PJ, Trejdosiewicz LK, Southgate J: Uroplakin gene expression by normal and neoplastic human urothelium. Am J Pathol. 1998, 153: 1957-1967.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  11. Rackley RR, Bandyopadhyay SK, Fazeli-Matin S, Shin MS, Appell R: Immunoregulatory potential of urothelium: characterization of NF-kappaB signal transduction. J Urol. 1999, 162: 1812-1816. 10.1097/00005392-199911000-00075.

    Article  PubMed  CAS  Google Scholar 

  12. Thomson JA, Itskovitz-Eldor J, Shapiro SS, Waknitz MA, Swiergiel JJ, Marshall VS, Jones JM: Embryonic stem cell lines derived from human blastocysts. Science. 1998, 282: 1145-1147. 10.1126/science.282.5391.1145.

    Article  PubMed  CAS  Google Scholar 

  13. Solter D, Knowles BB: Immunosurgery of mouse blastocyst. Proc Natl Acad Sci U S A. 1975, 72: 5099-5102.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  14. Hoffman DI, Zellman GL, Fair CC, Mayer JF, Zeitz JG, Gibbons WE, Turner JTG: Cryopreserved embryos in the United States and their availability for research. Fertility and Sterility. 2003, 79: 1063-1069. 10.1016/S0015-0282(03)00172-9.

    Article  PubMed  Google Scholar 

  15. Lanzendorf SE, Boyd CA, Wright DL, Muasher S, Oehninger S, Hodgen GD: Use of human gametes obtained from anonymous donors for the production of human embryonic stem cell lines. Fertil Steril. 2001, 76: 132-137. 10.1016/S0015-0282(01)01825-8.

    Article  PubMed  CAS  Google Scholar 

  16. Briggs RKTJ: Transplantation of living nuclei from blastula cells into enucleated frogs' eggs. Proceedings of the National Academy of Sciences of the United States of America. 1952, 38: 455-463.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  17. Gurdon JB: Adult frogs derived from the nuclei of single somatic cells. Dev Biol. 1962, 4: 256-273. 10.1016/0012-1606(62)90043-X.

    Article  PubMed  CAS  Google Scholar 

  18. Campbell KH, McWhir J, Ritchie WA, Wilmut I: Sheep cloned by nuclear transfer from a cultured cell line. Nature. 1996, 380: 64-66. 10.1038/380064a0.

    Article  PubMed  CAS  Google Scholar 

  19. Wilmut I, Schnieke AE, McWhir J, Kind AJ, Campbell KH: Viable offspring derived from fetal and adult mammalian cells. Nature. 1997, 385: 810-813. 10.1038/385810a0.

    Article  PubMed  CAS  Google Scholar 

  20. Cibelli JB, Stice SL, Golueke PJ, Kane JJ, Jerry J, Blackwell C, Ponce de Leon FA, Robl JM: Cloned transgenic calves produced from nonquiescent fetal fibroblasts. Science. 1998, 280: 1256-1258. 10.1126/science.280.5367.1256.

    Article  PubMed  CAS  Google Scholar 

  21. Baguisi A, Behboodi E, Melican DT, Pollock JS, Destrempes MM, Cammuso C, Williams JL, Nims SD, Porter CA, Midura P, Palacios MJ, Ayres SL, Denniston RS, Hayes ML, Ziomek CA, Meade HM, Godke RA, Gavin WG, Overstrom EW, Echelard Y: Production of goats by somatic cell nuclear transfer. Nat Biotechnol. 1999, 17: 456-461. 10.1038/8632.

    Article  PubMed  CAS  Google Scholar 

  22. Keefer CL, Keyston R, Lazaris A, Bhatia B, Begin I, Bilodeau AS, Zhou FJ, Kafidi N, Wang B, Baldassarre H, Karatzas CN: Production of cloned goats after nuclear transfer using adult somatic cells. Biol Reprod. 2002, 66: 199-203.

    Article  CAS  PubMed  Google Scholar 

  23. Wakayama T, Perry AC, Zuccotti M, Johnson KR, Yanagimachi R: Full-term development of mice from enucleated oocytes injected with cumulus cell nuclei. Nature. 1998, 394: 369-374. 10.1038/28615.

    Article  PubMed  CAS  Google Scholar 

  24. Betthauser J, Forsberg E, Augenstein M, Childs L, Eilertsen K, Enos J, Forsythe T, Golueke P, Jurgella G, Koppang R, Lesmeister T, Mallon K, Mell G, Misica P, Pace M, Pfister-Genskow M, Strelchenko N, Voelker G, Watt S, Thompson S, Bishop M: Production of cloned pigs from in vitro systems. Nat Biotechnol. 2000, 18: 1055-1059. 10.1038/80242.

    Article  PubMed  CAS  Google Scholar 

  25. Polejaeva IA, Chen SH, Vaught TD, Page RL, Mullins J, Ball S, Dai Y, Boone J, Walker S, Ayares DL, Colman A, Campbell KH: Cloned pigs produced by nuclear transfer from adult somatic cells. Nature. 2000, 407: 86-90. 10.1038/35024082.

    Article  PubMed  CAS  Google Scholar 

  26. Onishi A, Iwamoto M, Akita T, Mikawa S, Takeda K, Awata T, Hanada H, Perry AC: Pig cloning by microinjection of fetal fibroblast nuclei. Science. 2000, 289: 1188-1190. 10.1126/science.289.5482.1188.

    Article  PubMed  CAS  Google Scholar 

  27. De Sousa PA, Dobrinsky JR, Zhu J, Archibald AL, Ainslie A, Bosma W, Bowering J, Bracken J, Ferrier PM, Fletcher J, Gasparrini B, Harkness L, Johnston P, Ritchie M, Ritchie WA, Travers A, Albertini D, Dinnyes A, King TJ, Wilmut I: Somatic cell nuclear transfer in the pig: control of pronuclear formation and integration with improved methods for activation and maintenance of pregnancy. Biol Reprod. 2002, 66: 642-650.

    Article  CAS  PubMed  Google Scholar 

  28. Colman A, Kind A: Therapeutic cloning: concepts and practicalities. Trends Biotechnol. 2000, 18: 192-196. 10.1016/S0167-7799(00)01434-7.

    Article  PubMed  CAS  Google Scholar 

  29. Vogelstein B, Alberts B, Shine K: Genetics. Please don't call it cloning!. Science. 2002, 295: 1237-10.1126/science.1070247.

    Article  PubMed  Google Scholar 

  30. Hochedlinger K, Jaenisch R: Nuclear transplantation, embryonic stem cells, and the potential for cell therapy. N Engl J Med. 2003, 349: 275-286. 10.1056/NEJMra035397.

    Article  PubMed  CAS  Google Scholar 

  31. Lanza RP, Cibelli JB, West MD, Dorff E, Tauer C, Green RM: The ethical reasons for stem cell research. Science. 2001, 292: 1299-10.1126/science.292.5520.1299b.

    Article  PubMed  CAS  Google Scholar 

  32. Lanza RP, Cibelli JB, West MD: Prospects for the use of nuclear transfer in human transplantation. Nat Biotechnol. 1999, 17: 1171-1174. 10.1038/70709.

    Article  PubMed  CAS  Google Scholar 

  33. Solter D: Mammalian cloning: advances and limitations. Nat Rev Genet. 2000, 1: 199-207. 10.1038/35042066.

    Article  PubMed  CAS  Google Scholar 

  34. Rideout WM, Eggan K, Jaenisch R: Nuclear cloning and epigenetic reprogramming of the genome. Science. 2001, 293: 1093-1098. 10.1126/science.1063206.

    Article  PubMed  CAS  Google Scholar 

  35. Hochedlinger K, Jaenisch R: Nuclear transplantation: lessons from frogs and mice. Curr Opin Cell Biol. 2002, 14: 741-748. 10.1016/S0955-0674(02)00380-0.

    Article  PubMed  CAS  Google Scholar 

  36. Tsunoda Y, Kato Y: Recent progress and problems in animal cloning. Differentiation. 2002, 69: 158-161. 10.1046/j.1432-0436.2002.690405.x.

    Article  PubMed  CAS  Google Scholar 

  37. Kato Y, Tani T, Sotomaru Y, Kurokawa K, Kato J, Doguchi H, Yasue H, Tsunoda Y: Eight calves cloned from somatic cells of a single adult. Science. 1998, 282: 2095-2098. 10.1126/science.282.5396.2095.

    Article  PubMed  CAS  Google Scholar 

  38. Dinnyes A, De Sousa P, King T, Wilmut I: Somatic cell nuclear transfer: recent progress and challenges. Cloning Stem Cells. 2002, 4: 81-90. 10.1089/153623002753632075.

    Article  PubMed  CAS  Google Scholar 

  39. Young LE, Sinclair KD, Wilmut I: Large offspring syndrome in cattle and sheep. Rev Reprod. 1998, 3: 155-163. 10.1530/ror.0.0030155.

    Article  PubMed  CAS  Google Scholar 

  40. Cibelli JB, Campbell KH, Seidel GE, West MD, Lanza RP: The health profile of cloned animals. Nat Biotechnol. 2002, 20: 13-14. 10.1038/nbt0102-13.

    Article  PubMed  CAS  Google Scholar 

  41. Tamashiro KL, Wakayama T, Akutsu H, Yamazaki Y, Lachey JL, Wortman MD, Seeley RJ, D'Alessio DA, Woods SC, Yanagimachi R, Sakai RR: Cloned mice have an obese phenotype not transmitted to their offspring. Nat Med. 2002, 8: 262-267. 10.1038/nm0302-262.

    Article  PubMed  CAS  Google Scholar 

  42. Ogonuki N, Inoue K, Yamamoto Y, Noguchi Y, Tanemura K, Suzuki O, Nakayama H, Doi K, Ohtomo Y, Satoh M, Nishida A, Ogura A: Early death of mice cloned from somatic cells. Nat Genet. 2002, 30: 253-254. 10.1038/ng841.

    Article  PubMed  CAS  Google Scholar 

  43. Bortvin A, Eggan K, Skaletsky H, Akutsu H, Berry DL, Yanagimachi R, Page DC, Jaenisch R: Incomplete reactivation of Oct4-related genes in mouse embryos cloned from somatic nuclei. Development. 2003, 130: 1673-1680. 10.1242/dev.00366.

    Article  PubMed  CAS  Google Scholar 

  44. Boiani M, Eckardt S, Scholer HR, McLaughlin KJ: Oct4 distribution and level in mouse clones: consequences for pluripotency. Genes Dev. 2002, 16: 1209-1219. 10.1101/gad.966002.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  45. Lanza RP, Chung HY, Yoo JJ, Wettstein PJ, Blackwell C, Borson N, Hofmeister E, Schuch G, Soker S, Moraes CT, West MD, Atala A: Generation of histocompatible tissues using nuclear transplantation. Nat Biotechnol. 2002, 20: 689-696. 10.1038/nbt703.

    Article  PubMed  CAS  Google Scholar 

  46. Amiel GE, Atala A: Current and future modalities for functional renal replacement. Urol Clin North Am. 1999, 26: 235-46, xi.

    Article  CAS  PubMed  Google Scholar 

  47. Auchincloss H, Bonventre JV: Transplanting cloned cells into therapeutic promise. Nat Biotechnol. 2002, 20: 665-666. 10.1038/nbt0702-665.

    Article  PubMed  CAS  Google Scholar 

  48. Aebischer P, Ip TK, Panol G, Galletti PM: The bioartificial kidney: progress towards an ultrafiltration device with renal epithelial cells processing. Life Support Syst. 1987, 5: 159-168.

    PubMed  CAS  Google Scholar 

  49. Amiel GE, Yoo JJ, Atala A: Renal therapy using tissue-engineered constructs and gene delivery. World J Urol. 2000, 18: 71-79. 10.1007/s003450050013.

    Article  PubMed  CAS  Google Scholar 

  50. Humes HD, Buffington DA, MacKay SM, Funke AJ, Weitzel WF: Replacement of renal function in uremic animals with a tissue-engineered kidney. Nat Biotechnol. 1999, 17: 451-455. 10.1038/8626.

    Article  PubMed  CAS  Google Scholar 

  51. Ip TK, Aebischer P, Galletti PM: Cellular control of membrane permeability. Implications for a bioartificial renal tubule. ASAIO Trans. 1988, 34: 351-355.

    PubMed  CAS  Google Scholar 

  52. Joki T, Machluf M, Atala A, Zhu J, Seyfried NT, Dunn IF, Abe T, Carroll RS, Black PM: Continuous release of endostatin from microencapsulated engineered cells for tumor therapy. Nat Biotechnol. 2001, 19: 35-39. 10.1038/83481.

    Article  PubMed  CAS  Google Scholar 

  53. Lanza RP, Hayes JL, Chick WL: Encapsulated cell technology. Nat Biotechnol. 1996, 14: 1107-1111. 10.1038/nbt0996-1107.

    Article  PubMed  CAS  Google Scholar 

  54. MacKay SM, Funke AJ, Buffington DA, Humes HD: Tissue engineering of a bioartificial renal tubule. Asaio J. 1998, 44: 179-183.

    Article  CAS  PubMed  Google Scholar 

  55. Evans MJ, Gurer C, Loike JD, Wilmut I, Schnieke AE, Schon EA: Mitochondrial DNA genotypes in nuclear transfer-derived cloned sheep. Nat Genet. 1999, 23: 90-93. 10.1038/12696.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  56. Hiendleder S, Schmutz SM, Erhardt G, Green RD, Plante Y: Transmitochondrial differences and varying levels of heteroplasmy in nuclear transfer cloned cattle. Mol Reprod Dev. 1999, 54: 24-31. 10.1002/(SICI)1098-2795(199909)54:1<24::AID-MRD4>3.0.CO;2-S.

    Article  PubMed  CAS  Google Scholar 

  57. Steinborn R, Schinogl P, Zakhartchenko V, Achmann R, Schernthaner W, Stojkovic M, Wolf E, Muller M, Brem G: Mitochondrial DNA heteroplasmy in cloned cattle produced by fetal and adult cell cloning. Nat Genet. 2000, 25: 255-257. 10.1038/77000.

    Article  PubMed  CAS  Google Scholar 

  58. Fischer Lindahl K, Hermel E, Loveland BE, Wang CR: Maternally transmitted antigen of mice: a model transplantation antigen. Annu Rev Immunol. 1991, 9: 351-372. 10.1146/annurev.iy.09.040191.002031.

    Article  PubMed  CAS  Google Scholar 

  59. Hadley GA, Linders B, Mohanakumar T: Immunogenicity of MHC class I alloantigens expressed on parenchymal cells in the human kidney. Transplantation. 1992, 54: 537-542.

    Article  CAS  PubMed  Google Scholar 

  60. Yard BA, Kooymans-Couthino M, Reterink T, van den Elsen P, Paape ME, Bruyn JA, van Es LA, Daha MR, van der Woude FJ: Analysis of T cell lines from rejecting renal allografts. Kidney Int Suppl. 1993, 39: S133-8.

    PubMed  CAS  Google Scholar 

  61. Lanza R, Moore MA, Wakayama T, Perry AC, Shieh JH, Hendrikx J, Leri A, Chimenti S, Monsen A, Nurzynska D, West MD, Kajstura J, Anversa P: Regeneration of the infarcted heart with stem cells derived by nuclear transplantation. Circ Res. 2004, 94: 820-827. 10.1161/01.RES.0000120863.53562.DF.

    Article  PubMed  CAS  Google Scholar 

  62. Barberi T, Klivenyi P, Calingasan NY, Lee H, Kawamata H, Loonam K, Perrier AL, Bruses J, Rubio ME, Topf N, Tabar V, Harrison NL, Beal MF, Moore MA, Studer L: Neural subtype specification of fertilization and nuclear transfer embryonic stem cells and application in parkinsonian mice. Nat Biotechnol. 2003, 21: 1200-1207. 10.1038/nbt870.

    Article  PubMed  CAS  Google Scholar 

  63. Hwang WS, Ryu YJ, Park JH, Park ES, Lee EG, Koo JM, Jeon HY, Lee BC, Kang SK, Kim SJ, Ahn C, Hwang JH, Park KY, Cibelli JB, Moon SY: Evidence of a pluripotent human embryonic stem cell line derived from a cloned blastocyst. Science. 2004, 303: 1669-1674. 10.1126/science.1094515.

    Article  PubMed  CAS  Google Scholar 

  64. Plachot M, Mandelbaum J, de Grouchy J: [In vitro parthenogenesis in the human species]. Ann Genet. 1984, 27: 158-161.

    PubMed  CAS  Google Scholar 

  65. Strain L, Warner JP, Johnston T, Bonthron DT: A human parthenogenetic chimaera. Nat Genet. 1995, 11: 164-169. 10.1038/ng1095-164.

    Article  PubMed  CAS  Google Scholar 

  66. Kaufman MH, Barton SC, Surani MA: Normal postimplantation development of mouse parthenogenetic embryos to the forelimb bud stage. Nature. 1977, 265: 53-55.

    Article  CAS  PubMed  Google Scholar 

  67. Surani MA, Barton SC, Norris ML: Development of reconstituted mouse eggs suggests imprinting of the genome during gametogenesis. Nature. 1984, 308: 548-550. 10.1038/308548a0.

    Article  PubMed  CAS  Google Scholar 

  68. Ozil JP: The parthenogenetic development of rabbit oocytes after repetitive pulsatile electrical stimulation. Development. 1990, 109: 117-127.

    PubMed  CAS  Google Scholar 

  69. Marshall VS, Wilton LJ, Moore HD: Parthenogenetic activation of marmoset (Callithrix jacchus) oocytes and the development of marmoset parthenogenones in vitro and in vivo. Biol Reprod. 1998, 59: 1491-1497.

    Article  CAS  PubMed  Google Scholar 

  70. Surani MA, Kothary R, Allen ND, Singh PB, Fundele R, Ferguson-Smith AC, Barton SC: Genome imprinting and development in the mouse. Dev Suppl. 1990, 89-98.

    Google Scholar 

  71. Sasaki H, Jones PA, Chaillet JR, Ferguson-Smith AC, Barton SC, Reik W, Surani MA: Parental imprinting: potentially active chromatin of the repressed maternal allele of the mouse insulin-like growth factor II (Igf2) gene. Genes Dev. 1992, 6: 1843-1856.

    Article  CAS  PubMed  Google Scholar 

  72. Surani MA, Barton SC: Development of gynogenetic eggs in the mouse: implications for parthenogenetic embryos. Science. 1983, 222: 1034-1036.

    Article  CAS  PubMed  Google Scholar 

  73. Kumer SC, Vrana KE: Intricate regulation of tyrosine hydroxylase activity and gene expression. J Neurochem. 1996, 67: 443-462.

    Article  CAS  PubMed  Google Scholar 

  74. Cibelli JB, Grant KA, Chapman KB, Cunniff K, Worst T, Green HL, Walker SJ, Gutin PH, Vilner L, Tabar V, Dominko T, Kane J, Wettstein PJ, Lanza RP, Studer L, Vrana KE, West MD: Parthenogenetic stem cells in nonhuman primates. Science. 2002, 295: 819-10.1126/science.1065637.

    Article  PubMed  CAS  Google Scholar 

  75. Vrana KE, Hipp JD, Goss AM, McCool BA, Riddle DR, Walker SJ, Wettstein PJ, Studer LP, Tabar V, Cunniff K, Chapman K, Vilner L, West MD, Grant KA, Cibelli JB: Nonhuman primate parthenogenetic stem cells. Proc Natl Acad Sci U S A. 2003, 100 Suppl 1: 11911-11916. 10.1073/pnas.2034195100.

    Article  PubMed  CAS  Google Scholar 

  76. Klimanskaya IHJRKAWMAALR: Derivation and Comparative Assessment of Retinal Pigment Epithelium from Human Embryonic Stem Cells Using Transcriptomics. Cloning Stem Cells. 2004, 6: 217-245.

    Article  CAS  PubMed  Google Scholar 

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  1. Wake Forest Institute for Regenerative Medicine Wake Forest University School of Medicine, Winston Salem, North Carolina, USA

    Jason Hipp & Anthony Atala

  2. Wake Forest University School of Medicine Medical Center Blvd., Winston Salem, North Carolina, 27157, USA

    Anthony Atala

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Hipp, J., Atala, A. Tissue engineering, stem cells, cloning, and parthenogenesis: new paradigms for therapy . J Exp Clin Assist Reprod 1, 3 (2004). https://doi.org/10.1186/1743-1050-1-3

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Journal of Experimental & Clinical Assisted Reproduction

ISSN: 1743-1050