Skip to main content

Current Applications of Cellular Xenografts

  • Chapter
Xenotransplantation
  • 93 Accesses

Abstract

Cellular xenografting is a new type of transplantation therapy that is finding increasing application in the treatment of a variety of diseases. The hundreds of distinct cell types present in mammals offer the possibility of treating diseases, disorders, and injuries characterized by cell death or dysfunction. This chapter will focus on the unique aspects of xenogeneic cell therapy and will discuss the specific applications in current use in the clinic and in animal models.

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 84.99
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 109.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD 109.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. Gunsalus JR, Brady DA, Coulter SM, Gray BM, Edge ASB. Reduction of serum cholesterol in Watanabe rabbits by xenogeneic hepatocellular transplantation. Nat Med 1997; 3: 48–53.

    Article  PubMed  CAS  Google Scholar 

  2. Grossman M, Raper SE, Kozarsky K, et al. Successful ex vivo gene therapy directed to liver in a patient with familial hypercholesterolemia. Nat Genet 1994; 6: 335–341.

    Article  PubMed  CAS  Google Scholar 

  3. Fox IJ, Chowdhury R, Kaufman SS, et al. Treatment of the Crigler-Najjar syndrome Type I with hepatocyte transplantation. N Engl J Med 1998; 338: 1422–1426.

    Article  PubMed  CAS  Google Scholar 

  4. Li Q, Murphree SS, Willer SS, Bolli R, French BA. Gene therapy with bilirubinUDP-glucuronyltransferase in the Gunn rat model of Crigler-Najjar syndrome type 1. Hum Gen Ther 1998; 9: 497–505.

    Article  CAS  Google Scholar 

  5. Brittberg M, Lindahl A, Nilsson A, Ohlsson C, Isaksson O, Peterson L. Treatment of deep articular cartilage defects in the knee with autologous chondrocyte transplantation. N Engl J Med 1994; 331: 889–895.

    Article  PubMed  CAS  Google Scholar 

  6. Binette F, McQuaid DP, Haudenschild DR, Yaeger PC, McPherson JM, Tubo R. Expression of a stable articular cartilage phenotype without evidence of hypertrophy by adult human articular chondrocytes in vitro. J Ortop Res 1998; 28: 241–251.

    Google Scholar 

  7. Lindvall O, Sawle G, Widner H, et al. Evidence for long-term survival and function of dopaminergic grafts in progressive Parkinson’s disease. Ann Neurol 1994; 35: 172–180.

    Article  PubMed  CAS  Google Scholar 

  8. Lindvall O. Neural transplantation: a hope for patients with Parkinson’s disease. Neuroreport 1997; 8:iii-x.

    Article  Google Scholar 

  9. Ellias SA, Palmer EP, Kott HS, et al. Fetal porcine ventral mesencephalic transplantation for Parkinson’ s Disease: preliminary results. Mov Disord 1997; 12: 839–840.

    Google Scholar 

  10. Hillaire MS, Shannon K, Schumacher J, Starr et al. Transplantation of fetal porcine striatal cells in Huntington’s disease: preliminary safety and efficacy resuts. Neurology 1998; 50: 510. 008.

    Google Scholar 

  11. Archer DR, Cudden PA, Lipshitz D, Duncan LD. Myelination of the canine central nervous system by glial cell transplantation: a model for repair of human myelin disease. Nat Med 1997; 3: 54–59.

    Article  PubMed  CAS  Google Scholar 

  12. Kessler PD, Byrne BJ. Myoblast cell grafting into heart muscle: cellular biology and potential applications. Ann Rev Physiol 1999; 61: 219–242.

    Article  CAS  Google Scholar 

  13. Groth CG, Korsgren O, Tibell A, et al. Transplantation of porcine fetal pancreas to diabetic patients. Lancet 1994; 344: 1402–1404.

    Article  PubMed  CAS  Google Scholar 

  14. Gibson T. Zoografting - A curious chapter in the history of plastic surgery. Br J Plast Surg 1955; 8: 234.

    Article  PubMed  CAS  Google Scholar 

  15. Liu X, Federlin KF, Bretzel RG, Hering BJ, Brendel MD. Persistant reversal of diabetes by transplantation of fetal pig proislets into nude mice. Diabetes 1991; 40: 858–866.

    Article  PubMed  CAS  Google Scholar 

  16. Li H, Ricordi C, Demetris AJ, et al. Mixed xenogeneic chimerism (mouse + rat to mouse) to indice donor-specific tolerance to sequential or simultaneous islet xenografts. Transplantation 1994; 57: 592–598.

    PubMed  CAS  Google Scholar 

  17. Sachs DH. The pig as a potential xenograft donor. Pathol Biol 1994; 42: 217.

    PubMed  CAS  Google Scholar 

  18. Fishman J. Miniature swine as organ donors for man: strategies for prevention of xenotransplant-associated infections. Xenotransplantation 1994; 1: 47–57.

    Article  Google Scholar 

  19. Shamblott MJ, Axelman J, Wang M, et al. Derivation of pluripotential stem cells from cultured human primordial germ cells. Proc Natl Acad Sci USA 1998; 95:13, 726–13, 731.

    Google Scholar 

  20. Thomson JA, Itskovutz-Eldor J, Shapiro SS, et al. Embryonic stem cell lines derived from human blastocysts. Science 1998; 282: 1145–1147.

    Article  PubMed  CAS  Google Scholar 

  21. Makimo S, Fukuda K, Miyoshi S, et al. Cardiomyocytes can be generated from marrow stromal cells in vitro. J Clin Invest 1999; 103: 697–705.

    Article  Google Scholar 

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

    Article  PubMed  CAS  Google Scholar 

  23. Azizi SA, Stokes D, Augelli BJ, DiGirolamo C, Prockop DJ. Engraftment and migration of human bone marrow stromal cells implanted in the brains of albino rats–similarities to astrocyte grafts. Proc Natl Acad Sci USA 1998; 95: 3908–3913.

    Article  PubMed  CAS  Google Scholar 

  24. Bjornson CRR, Rietze RL, Reynolds BA, Magli MC, Vescovi AL. Turning brain into blood: a hematopoietic fate adopted by adult neural stem cells in vivo. Science 1999; 283: 534–537.

    Article  PubMed  CAS  Google Scholar 

  25. Isacson O, Deacon T. Neural transplantation studies reveal the brain’s capacity for continuous reconstruction. TINS 1997; 20: 477–482.

    PubMed  CAS  Google Scholar 

  26. Deacon T, Schumacher J, Dinsmore J, et al. Histological evidence of fetal pig neural cell survival after transplantation into a patient with Parkinson’s disease. Nat Med 1997; 3: 350–353.

    Article  PubMed  CAS  Google Scholar 

  27. Galpern WR, Burns LH, Deacon TW, Dinsmore J, Isacson O. Xenotransplantation of porcine fetal ventral mesencephalon in a rat model of Parkinson’s disease: functional recovery and graft morphology. Exp Neurol 1996; 140: 1–13.

    Article  PubMed  CAS  Google Scholar 

  28. Isacson O, Deacon TW, Pakzaban P, Galpern WR, Dinsmore J, Burns LH. Transplanted xenogeneic neural cells in neurodegenerative disease models exhibit remarkable axonal target specificity and distinct growth patterns of glial axonal fibers. Nat Med 1995; 1: 1189–1194.

    Article  PubMed  CAS  Google Scholar 

  29. Bluestone JA. New perspectives of CD28–B7-mediated T cell costimulation. Immunity 1995; 2: 555–559.

    Article  PubMed  CAS  Google Scholar 

  30. Kirk AD, Harlan DM, Armstrong NN, et al. CTLA4-Ig and anti-CD40 ligand prevent renal allograft rejection in primates. Proc Natl Acad Sci USA 1997; 94: 8789–8794.

    Article  PubMed  CAS  Google Scholar 

  31. Larsen CP, Elwood ET, Alexander DZ, et al. Long-Term Acceptance Of Skin and Cardiac Allografts After Blocking Cd40 and Cd28 Pathways. Nature 1996; 381: 434–438.

    Article  PubMed  CAS  Google Scholar 

  32. Lau HT, Yu M, Fontana A, Stoeckert CJ. Prevention of islet allograft rejection with engineered myoblasts expressing FasL in mice. Science 1996; 273: 109–112.

    Article  PubMed  CAS  Google Scholar 

  33. Allison J, Georgiou HM, Strasser A, Vaux DL. Transgenic expression of CD95 ligand on islet beta cells induces a granulocytic infiltration but does not confer immune privilege upon islet allografts. Proc Natl Acad Sci USA 1997; 94: 3943–3947.

    Article  PubMed  CAS  Google Scholar 

  34. Kang SM, Schneider DB, Lin ZH, et al. FAS ligand expression in Islets of Langerhans does not confer immune privilege and instead targets them for rapid destruction. Nat Med 1997; 3: 738–743.

    Article  PubMed  CAS  Google Scholar 

  35. Muruve DA, Nicolson AG, Manfro RC, Strom TB, Sukhatme VP, Libermann TA. Adenovirus-mediated expression of FAS ligand induces hepatic apoptosis after systemic administration and apoptosis of ex-vivo infected pancreatic islet allografts and isografts. Hum Gene Ther 1997; 8: 955–963.

    Article  PubMed  CAS  Google Scholar 

  36. Chen JJ, Sun Y, Nabel GJ. Regulation of the proinflammatory effects of Fas Ligand (CD95L). Science 1998; 282: 1714–1717.

    Article  PubMed  CAS  Google Scholar 

  37. Sloan-Lancaster J, Evavold BD, Allen PM. Induction of T-cell anergy by altered T-cell-receptor lignad on live antigen-presenting cells. Nature 1993; 363: 156–159.

    Article  PubMed  CAS  Google Scholar 

  38. Smith DM, Bluestone JA, Jeyarajah DR, et al. Inhibition of T cell activation by a monoclonal antibody reactive against the a3 domain of human MHC class I molecules. J Immunol 1994; 153: 1054–1063.

    PubMed  CAS  Google Scholar 

  39. Stock PG, Ascher NL, Bumgardner GL, Field MJ, Sutherland DER. Modulation of MHC class I antigen decreases pancreatic islet immunogenicity. J Surg Res 1989; 46: 317–321.

    Article  PubMed  CAS  Google Scholar 

  40. DerSimonian H, Yatko C, Kohnson E, Rodrigue-Way A, Edge ASB. Human anti-porcine T cell response: the role of anti-class I antibody masking in graft tolerance to cell transplantation. J Immunol 1999; 162: 6993–7001.

    PubMed  CAS  Google Scholar 

  41. Bach FH, Winkler H, Ferran C, Hancock WW, Robson SC. Delayed xenograft rejection. Immunol Today 1996; 17: 379–384.

    Article  PubMed  CAS  Google Scholar 

  42. Galili U. Interaction of the natural anti-Gal antibody with alpha-galactosyl epitopes: a major obstacle for xenotransplantation in humans. Immunol Today 1993; 14: 480–482.

    Article  PubMed  CAS  Google Scholar 

  43. LaVecchio JL, XDunne SC, Edge ASB. Enzymatic removal of alpha-galactosyl epitopes from porcine endothelial cells diminishes the cytotoxic effect of natural antibodies. Transplantation 1995; 60: 841–847.

    PubMed  CAS  Google Scholar 

  44. Seebach JD, Comrack C, Germana S, LeGuern C, Sachs DH, DerSimonian H. HLACw3 expression on porcine endothelial cells protects against xenogeneic cytotoxicity mediated by a subset of human NK cells. J Immunol 1997; 159: 3655–3661.

    PubMed  CAS  Google Scholar 

  45. Donnelly CE, Yatko C, Johnson EW, Edge ASB. Human natural killer cells account for non-MHC class I restricted cytolysis of porcine cells. Cell Immunol 1997; 175: 171–178.

    Article  PubMed  CAS  Google Scholar 

  46. Sullivan JA, Oettinger HF, Sachs DH, Edge ASB. Analysis of ploymorphism in porcine MHC class I genes. Alterations in signals recognized by human cytotoxic lymphocytes. J Immunol 1997; 159: 2318–2326.

    PubMed  CAS  Google Scholar 

  47. Bellgrau D, Gold D, Selawry H, Moore J, Franzusoff A, Duke RC. A role for CD95 ligand in preventing graft rejection. Nature 1995; 377: 630–632.

    Article  PubMed  CAS  Google Scholar 

  48. Griffith TS, Brunner T, Fletcher SM, Green DR, Ferguson TA. Fas ligand-induced apoptosis as a mechanism of immune privilege [see comments]. Science 1995; 270: 1189–1192.

    Article  PubMed  CAS  Google Scholar 

  49. Bach FH, Robson SC, Winkler H, et al. Barriers to xenotransplantation. Nat Med 1995; 1: 869–873.

    Article  PubMed  CAS  Google Scholar 

  50. Neethling FA, Koren E, Ye Y, et al. Protection of pig kidney (PK15) cells from the cytotoxic effect of anti-pig antibodies by a-galactosyl oligosaccharides. Transplantation 1994; 57: 959–963.

    Article  PubMed  CAS  Google Scholar 

  51. Mirenda V, Le Mauff B, Cassard A, et al. Intact pig pancreatic islet function in the presence of human xenoreactive natural antibody binding and complement activation. Transplantation 1997; 63: 1452–1462.

    Article  PubMed  CAS  Google Scholar 

  52. Markmann JF, Tomaszewski J, Posselt AM, et al. The effect of islet cell culture in vitro at 24°C on graft survival and MHC antigen expression. Transplantation 1990; 49: 272–277.

    Article  PubMed  CAS  Google Scholar 

  53. Bach FH, Fineberg HV. Call for moratorium on xenotransplants. Nature 1998; 391: 326.

    Article  PubMed  CAS  Google Scholar 

  54. Patience C, Takeuchi Y, Weiss RA. Infection of human cells by an endogenous retrovirus of pigs. Nat Med 1997; 3: 282–286.

    Article  PubMed  CAS  Google Scholar 

  55. Martin U, Keisig V, Blusch JH, et al. Expression of pig endogenous retrovirus by primary porcine endothelial cells and infection of human cells. Lancet 1998; 352: 692–694.

    Article  PubMed  CAS  Google Scholar 

  56. Heheine W, Tibell A, Switzer WM, et al. No evidence of infection with porcine endogenous retrovirus in recipients of porcine islet-cell xenografts. Lancet 1998; 352: 695–699.

    Article  Google Scholar 

  57. Patience C, Patton GS, Takeuchi Y, et al. No evidence of pig DNA or retroviral infection in patients with short-term extracorporeal connection to pig kidneys. Lancet 1998; 352: 699–701.

    Article  PubMed  CAS  Google Scholar 

  58. Oettinger HF, Rodrigue-Way A, Bousquet JJ, Edge ASB. Porcine repeat element DNA: in situ detection of xenotransplanted cells. Cell Transplant 1995; 4: 253–256.

    Article  PubMed  CAS  Google Scholar 

  59. Gupta S, Rajvanshi P, Lee C. Integration of transplanted hepatocytes into host liver plates demonstrated with dipeptidyl peptidase IV-deficient rats. Proc Natl Acad Sci USA 1995; 92: 5860–5864.

    Article  PubMed  CAS  Google Scholar 

  60. Stefan AM, Coulter S, Gray B, et al. Xenogeneic transplantation of porcine hepatocytes into the CC14 rat model. Cell Transplant 1999; 8: 649–659.

    PubMed  CAS  Google Scholar 

  61. Gupta S, Gorla GR, Irani AN. Hepatocyte transplantation: emerging insights into mechanisms of liver repopulation and their relevance to potential therapies. J Hepatol 1999; 30: 162–170.

    Article  PubMed  CAS  Google Scholar 

  62. Strom SC, Fisher RA, Thompson MT, et al. Hepatocyte transplantation as a bridge to orthotopic liver transplantation in terminal liver failure. Transplantation 1997; 63: 559–569.

    Article  PubMed  CAS  Google Scholar 

  63. Bilir BM, Guenette D, Ostrowska A, et al. Percutaneous hepatocyte transplantation (PHT) in liver failure. Hepatology 1997; 26: 252A.

    Google Scholar 

  64. Lane C, Boulton M, Marshall J. Transplantation of retinal pigment epithelium using a pars plana approach. Eye 1989; 3: 27–32.

    Article  PubMed  Google Scholar 

  65. Gouras P, Algvere P. Retinal cell transplantation in the macula: new techniques. Vision Res 1996; 36: 4121–4125.

    Article  PubMed  CAS  Google Scholar 

  66. Algvere PV, Berglin L, Gouras P, Sheng Y. Transplantation of fetal retinal pigment epithelium in age-related macular degeneration with subfoveal neovascularization. Graefe’s Arch Clin Exp Ophthalmol 1994; 232: 707–716.

    Article  PubMed  CAS  Google Scholar 

  67. Li R-K, Jia Z-Q, Weisel RD, et al. Cardiomyocyte transplantation improves heart function. Ann Thorac Surg 1996; 62: 654–661.

    Article  PubMed  CAS  Google Scholar 

  68. Steel KP. Progress in progressive hearing loss. Science 1998; 279: 1870–1871.

    Article  PubMed  CAS  Google Scholar 

  69. Ruth RA. Evaluation of sensorineural hearing loss. Comp Ther 1997; 23: 742–749.

    CAS  Google Scholar 

  70. Starr A, Picton TW, Sininger Y, Hood LJ, Berlin CI. Auditory Neuropathy Brain 1996; 119: 741–743.

    Article  Google Scholar 

  71. 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.

    Article  PubMed  CAS  Google Scholar 

  72. Oberpenning F, Meng J, Yoo JJ, Atala A. Nat Biotechnol 1999; 17: 149–155.

    Article  PubMed  CAS  Google Scholar 

  73. Beauchamp JR, Morgan JE, Pagel CN, Partridge TA. Dynamics of myoblast transplantation reveal a discrete minority of precursors with stem cell-like properties as the myogenic source. J Cell Biol 1999; 144: 1113–1121.

    Article  PubMed  CAS  Google Scholar 

  74. Qu Z, Balkir L, JDeutekom CTV, Robbins PD, Pruchnic R, Huard J. Development of approaches to improve cell survival in myoblast transfer therapy. J Cell Biol 1998; 142: 1257–1267.

    Article  PubMed  CAS  Google Scholar 

  75. Mignon A, Guidotti JE, Mitchell C, et al. Selective repopulation of normal mouse liver by Fas/CD95-resistant hepatocytes. Nat Med 1998; 10:1 185–1 188.

    Article  Google Scholar 

  76. Gussoni E, Blau HM, Kunkel LM. The fate of individual myohlasts after transplantation into muscles of DMD patients. Nat Med 1997; 3: 970–977.

    Article  PubMed  CAS  Google Scholar 

Download references

Authors

Editor information

Editors and Affiliations

Rights and permissions

Reprints and permissions

Copyright information

© 2002 Springer Science+Business Media New York

About this chapter

Cite this chapter

Edge, A.S.B. (2002). Current Applications of Cellular Xenografts. In: Platt, J.L. (eds) Xenotransplantation. Humana Press, Totowa, NJ. https://doi.org/10.1007/978-1-59259-166-4_12

Download citation

  • DOI: https://doi.org/10.1007/978-1-59259-166-4_12

  • Publisher Name: Humana Press, Totowa, NJ

  • Print ISBN: 978-1-61737-127-1

  • Online ISBN: 978-1-59259-166-4

  • eBook Packages: Springer Book Archive

Publish with us

Policies and ethics