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Plasticity of Human Stem Cells in the Fetal Sheep Model of Human Stem Cell Transplantation

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Abstract

Experimental models that allow the evaluation of the full potential of stem cells under normal physiological conditions and in the absence of genetic or injury-induced dysfunction would serve as valuable tools for the study of the mechanisms underlying stem cell differentiation. Ideally, such a model would also permit the robust formation of donor-derived tissue-specific cells. Because studies have shown that the differentiation of stem cells into cells of a different germinal layer is highly inefficient in the absence of selective pressure, it is very unlikely that a healthy adult animal can fulfill these requirements. In this review, we describe the advantages of the permissive aspects of the developing preimmune fetus in the early gestational age that led us to develop the sheep as a large-animal model of human stem cell plasticity.

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References

  1. Lagasse E, Connors H, Al-Dhalimy M, et al. Purified hematopoietic stem cells can differentiate into hepatocytes in vivo.Nat Med. 2000;6:1229–1234.

    Article  CAS  PubMed  Google Scholar 

  2. Petersen BE, Bowen WC, Patrene KD, et al. Bone marrow as a potential source of hepatic oval cells.Science. 1999;284:1168–1170.

    Article  CAS  PubMed  Google Scholar 

  3. Theise ND, Badve S, Saxena R, et al. Derivation of hepatocytes from bone marrow cells of mice after radiation-induced myeloablation.Hepatology. 2000;31:235–240.

    Article  CAS  PubMed  Google Scholar 

  4. Krause DS, Theise ND, Collector MI, et al. Multi-organ, multi-lineage engraftment by a single bone marrow-derived stem cell.Cell. 2001;105:369–377.

    Article  CAS  PubMed  Google Scholar 

  5. Wagers AJ, Sherwood RI, Christensen JL, Weissman IL. Little evidence for developmental plasticity of adult hematopoietic stem cells.Science. 2002;297:2256–2259.

    Article  CAS  PubMed  Google Scholar 

  6. Wang X, Montini E, Al-Dhalimy M, Lagasse E, Finegold M, Grompe M. Kinetics of liver repopulation after bone marrow transplantation.Am J Pathol. 2002;161:565–574.

    Article  PubMed  PubMed Central  Google Scholar 

  7. Mallet VO, Mitchell C, Mezey E, et al. Bone marrow transplantation in mice leads to a minor population of hepatocytes that can be selectively amplified in vivo.Hepatology. 2002;35:799–804.

    Article  PubMed  Google Scholar 

  8. Wang X, Ge S, McNamara G, Hao QL, Crooks GM, Nolta JA. Albumin-expressing hepatocyte-like cells develop in the livers of immune-deficient mice that received transplants of highly purified human hematopoietic stem cells.Blood. 2003;101:4201–4208.

    Article  PubMed  CAS  Google Scholar 

  9. Theise ND, Nimmakayalu M, Gardner R, et al. Liver from bone marrow in humans.Hepatology. 2000;32:11–16.

    Article  CAS  PubMed  Google Scholar 

  10. Alison MR, Poulsom R, Jeffery R, et al. Hepatocytes from nonhepatic adult stem cells.Nature. 2000;406:257.

    Article  CAS  PubMed  Google Scholar 

  11. Korbling M, Katz RL, Khanna A, et al. Hepatocytes and epithelial cells of donor origin in recipients of peripheral-blood stem cells.N Engl J Med. 2002;346:738–746.

    Article  PubMed  Google Scholar 

  12. Danet GH, Luongo JL, Butler G, et al. C1qRp defines a new human stem cell population with hematopoietic and hepatic potential.Proc Natl Acad Sci USA. 2002;99:10441–10445.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  13. Schwartz RE, Reyes M, Koodie L, et al. Multipotent adult progenitor cells from bone marrow differentiate into functional hepatocyte-like cells.J Clin Invest. 2002;109:1291–1302.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  14. Almeida-Porada G, El Shabrawy D, Porada C, Zanjani ED. Differentiative potential of human metanephric mesenchymal cells.Exp Hematol. 2002;30:1454–1462.

    Article  PubMed  CAS  Google Scholar 

  15. Ferrari G, Cusella-De Angelis G, Coletta M, et al. Muscle regeneration by bone marrow-derived myogenic progenitors.Science. 1998;279:1528–1530.

    Article  CAS  PubMed  Google Scholar 

  16. Bjornson CRR, Rietze RL, Reynolds BA, et al. Turning brain into blood: a hematopoietic fate adopted by adult neural stem cells in vivo.Science. 1999;283:534–537.

    Article  CAS  PubMed  Google Scholar 

  17. Bittner RE, Popoff I, Shorny S, et al. Dystrophin expression in heterozygous mdx/+ mice indicates imprinting of X chromosome inactivation by parent-of-origin-, tissue-, strain- and position-dependent factors.Anat Embryol (Berl). 1997;195:175–182.

    Article  PubMed  CAS  Google Scholar 

  18. Gussoni E, Soneoka Y, Strickland CD, et al. Dystrophin expression in the mdx mouse restored by stem cell transplantation.Nature. 1999;401:390–394.

    CAS  PubMed  Google Scholar 

  19. Clarke DL, Johansson CB, Wilbertz J, et al. Generalized potential of adult neural stem cells.Science. 2000;288:1660–1663.

    Article  PubMed  CAS  Google Scholar 

  20. Watt FM. Epidermal stem cells: markers, patterning and the control of stem cell fate.Philos Trans R Soc Lond B Biol Sci. 1998;353:831–837.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  21. Ormerod EJ, Rudland PS. Regeneration of mammary glands in vivo from isolated mammary ducts.J Embryol Exp Morphol. 1986;96:229–243.

    PubMed  CAS  Google Scholar 

  22. Seale P, Rudnicki MA. A new look at the origin, function, and “stem-cell” status of muscle satellite cells.Dev Biol. 2000;218:115–124.

    Article  PubMed  CAS  Google Scholar 

  23. Gage FH, Ray J, Fisher LJ. Isolation, characterization, and use of stem cells from the CNS.Annu Rev Neurosci. 1995;18:159–192.

    Article  PubMed  CAS  Google Scholar 

  24. Eriksson PS, Perfilieva E, Bjork-Eriksson T, et al. Neurogenesis in the adult human hippocampus.Nat Med. 1998;4:1313–1317.

    Article  PubMed  CAS  Google Scholar 

  25. Block GD, Locker J, Bowen WC, et al. Population expansion, clonal growth, and specific differentiation patterns in primary cultures of hepatocytes induced by HGF/SF, EGF and TGFα in a chemically defined (HGM) medium.J Cell Biol. 1996;132:1133–1149.

    Article  PubMed  CAS  Google Scholar 

  26. Reid GM, Tervit HM. Sudden infant death syndrome: near weightlessness and delayed neural transformation.Med Hypotheses. 1996;46:383–387.

    Article  PubMed  CAS  Google Scholar 

  27. Serova LV. The maternal-fetal system as an object for the study of mechanisms of the physiologic effect of weightlessness [in Russian].Kosm BiolAviakosm Med. 1987;21:63–66.

    CAS  Google Scholar 

  28. Wood C. Weightlessness: its implications for the human fetus.Obstet Gynaecol Br Commonw. 1970;77:333–336.

    Article  CAS  Google Scholar 

  29. Susse HJ, Wurterle A. The shifting center of gravity in the growing fetus [in German].Zentralbl Gynakol. 1967;89:980–984.

    PubMed  CAS  Google Scholar 

  30. Hammond TG, Benes E, O'Reilly KC, et al. Mechanical culture conditions effect gene expression: gravity-induced changes on the space shuttle.Physiol Genomics. 2000;3:163–173.

    Article  PubMed  CAS  Google Scholar 

  31. de Groot RP, Rijken PJ, den Hertog J, et al. Microgravity decreases c-fos induction and serum response element activity.J Cell Sci. 1990;97:33–38.

    Google Scholar 

  32. de Groot RP, Rijken PJ, den Hertog J, et al. Nuclear responses to protein kinase C signal transduction are sensitive to gravity.Exp Cell Res. 1991;197:87–90.

    Article  Google Scholar 

  33. Walther I, Pippia P, Meloni MA, et al. Simulated microgravity inhibits the genetic expression of interleukin-2 and its receptor in mitogen-activated T lymphocytes.FEBS Lett. 1998;436:115–118.

    Article  PubMed  CAS  Google Scholar 

  34. Hammond TG, Lewis FC, Goodwin TJ, et al. Gene expression in space.Nat Med. 1999;5:359.

    Article  PubMed  CAS  Google Scholar 

  35. Stein GS, van Wijnen AJ, Stein JL, et al. Implications for interrelationships between nuclear architecture and control of gene expression under microgravity conditions.FASEB J. 1999;13:157–166.

    Article  Google Scholar 

  36. Margolis L, Hatfill S, Chuaqui R, et al. Long term organ culture of human prostate tissue in a NASA-designed rotating wall bioreactor.J Urol. 1999;161:290–297.

    Article  PubMed  CAS  Google Scholar 

  37. Akins RE, Schroedl NA, Gonda SR, et al. Neonatal rat heart cells cultured in simulated microgravity.In Vitro Cell Dev Biol Anim. 1997;33:337–343.

    Article  PubMed  CAS  Google Scholar 

  38. Zanjani ED, Pallavicini MG, Ascensao JL, et al. Engraftment and long-term expression of human fetal hematopoietic stem cells in sheep following transplantation in utero.J Clin Invest. 1992;89:1178–1188.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  39. Civin CI, Almeida-Porada G, Lee M-J, Olweus J, Terstappen LWMM, Zanjani ED. Sustained, retransplantable, multilineage engraftment of highly purified adult human bone marrow stem cells in vivo.Blood. 1996;88:4102–4109.

    PubMed  CAS  Google Scholar 

  40. Yin AH, Miragi AS, Zanjani ED, et al. AC133, A novel marker for human hematopoietic stem and progenitor cells.Blood. 1997;90:5002–5012.

    PubMed  CAS  Google Scholar 

  41. Shimizu Y, Ogawa M, Kobayashi M, Almeida-Porada G, Zanjani ED. Engraftment of cultured human hematopoietic cells in sheep.Blood. 1998;91:3688–3692.

    PubMed  CAS  Google Scholar 

  42. Zanjani ED, Almeida-Porada G, Livingston AG, Flake AW, Ogawa M. Human bone marrow CD34: cells engraft in vivo and undergo multilineage expression including giving rise to CD34+ cells.Exp Hematol. 1998;26:353–360.

    PubMed  CAS  Google Scholar 

  43. Giesert C, Almeida-Porada G, Scheffold A, Kanz L, Zanjani ED, Buhring HJ. The monoclonal antibody W7C5 defines a novel surface antigen on hematopoietic stem cells.Ann N Y Acad Sci. 2001;938:175–183.

    Article  PubMed  CAS  Google Scholar 

  44. Verfaillie CM, Almeida-Porada G, Wissink S, Zanjani ED. Kinetics of engraftment of CD34- and CD34+ cells from mobilized blood differs from that of CD34- and CD34+ cells from bone marrow.Exp Hematol. 2000;28:1071–1079.

    Article  PubMed  CAS  Google Scholar 

  45. Almeida-Porada G, Hoffman R, Manalo P, et al. Detection of human cells in human/sheep chimeric lambs with in vitro human stroma-forming potential.Exp Hematol. 1996;24:482–487.

    PubMed  CAS  Google Scholar 

  46. Zanjani ED, Porada P, Crapnell KB, et al. Production of human hepatocytes by human CD34+/- cells in vivo [abstract].Blood. 2000;96:494a..

    Google Scholar 

  47. Almeida-Porada G, Crapnell K, Porada C, et al. Transplantation of human neuronal stem cells into fetal sheep give rise to hematopoietic cells in vivo [abstract].Blood. 1999;94:129a.

    Google Scholar 

  48. Almeida-Porada G, Crapnell K, Porada C, et al. In vivo hematopoietic potential of human neuronal stem cells.Exp Hematol. 2000;28:61a.

    Article  Google Scholar 

  49. Reyes M, Lund T, Lenvik T, Aguiar D, Koodie L, Verfaillie CM. Purification and ex vivo expansion of postnatal human marrow mesodermal progenitor cells.Blood. 2000;98:2615–2625.

    Article  Google Scholar 

  50. Liechty KW, MacKenzie, TC, Shaaban AF, et al. Human mesenchymal stem cells engraft and demonstrate site-specific differentiation after in utero transplantation in sheep.Nat Med. 2000;6:1282–1286.

    Article  PubMed  CAS  Google Scholar 

  51. Kopen GC, Prockop DJ, Phinney DG. Marrow stromal cells migrate throughout forebrain and cerebellum, and they differentiate into astrocytes after injection into neonatal mouse brains.Proc Natl Acad Sci USA. 1999;96:10711–10716.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  52. Sanchez-Ramos J, Song S, Cardozo-Pelaez F, et al. Adult bone marrow stromal cells differentiate into neural cells in vitro.Exp Neurol. 2000;164:247–256.

    Article  CAS  PubMed  Google Scholar 

  53. Woodbury D, Schwarz EJ, Prockop DJ, Black IB. Adult rat and human bone marrow stromal cells differentiate into neurons.J Neurosci Res. 2000;61:364–370.

    Article  CAS  PubMed  Google Scholar 

  54. Pittenger MF, Mackay AM, Beck SC, et al. Multilineage potential of adult human mesenchymal stem cells.Science. 1999;284:143–147.

    Article  PubMed  CAS  Google Scholar 

  55. Mackay AM, Beck SC, Murphy JM, Barry FP, Chichester CO, Pittenger MF. Chondrogenic differentiation of cultured human mesenchymal stem cells from marrow.Tissue Eng. 1998;4:415–428.

    Article  PubMed  CAS  Google Scholar 

  56. Almeida-Porada G, Porada C, El Shabrawy D, Simmons PJ, Zanjani ED. Human marrow stromal cells (MSC) represent a latent pool of stem cells capable of generating long-term hematopoietic cells [abstract].Blood. 2001;98:713a.

    Google Scholar 

  57. Almeida-Porada G, El Shabrawy D, Porada C, Ascensao JL, Zanjani ED. Clonally derived marrow stromal cells (MSC) populations are able to differentiate into blood, liver and skin cells [abstract].Blood. 2001;98:791a.

    Google Scholar 

  58. Wang X, Willenbring H, Akkari Y, et al. Cell fusion is the principal source of bone-marrow-derived hepatocytes.Nature. 2003;422:897–901.

    Article  CAS  PubMed  Google Scholar 

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Authors and Affiliations

  1. Department of Animal Biotechnology, University of Nevada Reno, Mail Stop 202, 89557-0104, Reno, NY, USA

    Graça Almeida-Porada, Christopher Porada & Esmail D. Zanjani

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  1. Graça Almeida-Porada
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  2. Christopher Porada
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  3. Esmail D. Zanjani
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Correspondence to Graça Almeida-Porada.

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Almeida-Porada, G., Porada, C. & Zanjani, E.D. Plasticity of Human Stem Cells in the Fetal Sheep Model of Human Stem Cell Transplantation. Int J Hematol 79, 1–6 (2004). https://doi.org/10.1007/BF02983526

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  • DOI: https://doi.org/10.1007/BF02983526

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