Skip to main content
SpringerLink
Log in
Book cover

Mesenchymal Stromal Cells pp 237–258Cite as

MSC Studies in Large-Animal Models

  • Chapter
  • First Online:

  • 1437 Accesses

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

Abstract

Mesenchymal stromal cells found within bone marrow, fat, and other tissues are a population of cells with the potential to mediate therapeutic outcomes based on differentiation into multiple cell lineages or through paracrine-mediated mechanisms that influence angiogenesis, apoptosis, or immune response. Currently, mesenchymal stromal cells are being widely investigated for numerous tissue engineering and regenerative medicine applications. Appropriate animal models will be crucial to the development and evaluation of regenerative medicine-based treatments and eventual cures for debilitating diseases. Here, we summarize the ongoing research focused on studying the biological and therapeutic potential of mesenchymal stromal cells in large-animal models.

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

Chapter
USD   29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD   169.00
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD   219.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD   219.99
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

Learn about institutional subscriptions

References

  1. Fischer EM, Layrolle P, Van Blitterswijk CA, De Bruijn JD (2003) Bone formation by ­mesenchymal progenitor cells cultured on dense and microporous hydroxyapatite particles. Tissue Eng 9(6):1179–1188

    Article  PubMed  CAS  Google Scholar 

  2. Murphy JM, Fink DJ, Hunziker EB, Barry FP (2003) Stem cell therapy in a caprine model of osteoarthritis. Arthritis Rheum 48(12):3464–3474

    Article  PubMed  Google Scholar 

  3. Kadiyala S, Young RG, Thiede MA, Bruder SP (1997) Culture expanded canine mesenchymal stem cells possess osteochondrogenic potential in vivo and in vitro. Cell Transplant 6(2):125–134

    Article  PubMed  CAS  Google Scholar 

  4. Martin DR, Cox NR, Hathcock TL, Niemeyer GP, Baker HJ (2002) Isolation and characterization of multipotential mesenchymal stem cells from feline bone marrow. Exp Hematol 30(8):879–886

    Article  PubMed  CAS  Google Scholar 

  5. Jessop HL, Noble BS, Cryer A (1994) The differentiation of a potential mesenchymal stem cell population within ovine bone marrow. Biochem Soc Trans 22(3):248S

    PubMed  CAS  Google Scholar 

  6. McCarty RC, Gronthos S, Zannettino AC, Foster BK, Xian CJ (2009) Characterisation and developmental potential of ovine bone marrow derived mesenchymal stem cells. J Cell Physiol 219(2):324–333

    Article  PubMed  CAS  Google Scholar 

  7. Weir C, Morel-Kopp MC, Gill A, Tinworth K, Ladd L, Hunyor SN et al (2008) Mesenchymal stem cells: isolation, characterisation and in vivo fluorescent dye tracking. Heart Lung Circ 17(5):395–403

    Article  PubMed  Google Scholar 

  8. Bosch P, Pratt SL, Stice SL (2006) Isolation, characterization, gene modification, and nuclear reprogramming of porcine mesenchymal stem cells. Biol Reprod 74(1):46–57

    Article  PubMed  CAS  Google Scholar 

  9. Vacanti V, Kong E, Suzuki G, Sato K, Canty JM, Lee T (2005) Phenotypic changes of adult porcine mesenchymal stem cells induced by prolonged passaging in culture. J Cell Physiol 205(2):194–201

    Article  PubMed  CAS  Google Scholar 

  10. Arnhold SJ, Goletz I, Klein H, Stumpf G, Beluche LA, Rohde C et al (2007) Isolation and characterization of bone marrow-derived equine mesenchymal stem cells. Am J Vet Res 68(10):1095–1105

    Article  PubMed  CAS  Google Scholar 

  11. Vidal MA, Kilroy GE, Johnson JR, Lopez MJ, Moore RM, Gimble JM (2006) Cell growth characteristics and differentiation frequency of adherent equine bone marrow-derived mesenchymal stromal cells: adipogenic and osteogenic capacity. Vet Surg 35(7):601–610

    Article  PubMed  Google Scholar 

  12. Bosnakovski D, Mizuno M, Kim G, Takagi S, Okumura M, Fujinaga T (2005) Isolation and multilineage differentiation of bovine bone marrow mesenchymal stem cells. Cell Tissue Res 319(2):243–253

    Article  PubMed  Google Scholar 

  13. Izadpanah R, Joswig T, Tsien F, Dufour J, Kirijan JC, Bunnell BA (2005) Characterization of multipotent mesenchymal stem cells from the bone marrow of rhesus macaques. Stem Cells Dev 14(4):440–451

    Article  PubMed  CAS  Google Scholar 

  14. Izadpanah R, Trygg C, Patel B, Kriedt C, Dufour J, Gimble JM et al (2006) Biologic properties of mesenchymal stem cells derived from bone marrow and adipose tissue. J Cell Biochem 99(5):1285–1297

    Article  PubMed  CAS  Google Scholar 

  15. Lee CC, Ye F, Tarantal AF (2006) Comparison of growth and differentiation of fetal and adult rhesus monkey mesenchymal stem cells. Stem Cells Dev 15(2):209–220

    Article  PubMed  CAS  Google Scholar 

  16. Pearce AI, Richards RG, Milz S, Schneider E, Pearce SG (2007) Animal models for implant biomaterial research in bone: a review. Eur Cell Mater 13:1–10

    PubMed  CAS  Google Scholar 

  17. Aerssens J, Boonen S, Lowet G, Dequeker J (1998) Interspecies differences in bone composition, density, and quality: potential implications for in vivo bone research. Endocrinology 139(2):663–670

    Article  PubMed  CAS  Google Scholar 

  18. Mankani MH, Kuznetsov SA, Shannon B, Nalla RK, Ritchie RO, Qin Y et al (2006) Canine cranial reconstruction using autologous bone marrow stromal cells. Am J Pathol 168(2):542–550

    Article  PubMed  Google Scholar 

  19. Cui L, Liu B, Liu G, Zhang W, Cen L, Sun J et al (2007) Repair of cranial bone defects with adipose derived stem cells and coral scaffold in a canine model. Biomaterials 28(36):5477–5486

    Article  PubMed  CAS  Google Scholar 

  20. Bruder SP, Kraus KH, Goldberg VM, Kadiyala S (1998) The effect of implants loaded with autologous mesenchymal stem cells on the healing of canine segmental bone defects. J Bone Joint Surg Am 80(7):985–996

    PubMed  CAS  Google Scholar 

  21. Arinzeh TL, Peter SJ, Archambault MP, van den Bos C, Gordon S, Kraus K et al (2003) Allogeneic mesenchymal stem cells regenerate bone in a critical-sized canine segmental defect. J Bone Joint Surg Am 85-A(10):1927–1935

    PubMed  Google Scholar 

  22. Jang BJ, Byeon YE, Lim JH, Ryu HH, Kim WH, Koyama Y et al (2008) Implantation of canine umbilical cord blood-derived mesenchymal stem cells mixed with beta-tricalcium phosphate enhances osteogenesis in bone defect model dogs. J Vet Sci 9(4):387–393

    Article  PubMed  Google Scholar 

  23. Yamazoe K, Mishima H, Torigoe K, Iijima H, Watanabe K, Sakai H et al (2007) Effects of atelocollagen gel containing bone marrow-derived stromal cells on repair of osteochondral defect in a dog. J Vet Med Sci 69(8):835–839

    Article  PubMed  CAS  Google Scholar 

  24. An Y, Friedman R (1999) Animal selections in orthopaedic research. In: An Y, Friedman R (eds) Animal models in orthopaedic research. CRC Press, Boca Raton, pp 39–57

    Google Scholar 

  25. An YH, Woolf SK, Friedman RJ (2000) Pre-clinical in vivo evaluation of orthopaedic bioabsorbable devices. Biomaterials 21(24):2635–2652

    Article  PubMed  CAS  Google Scholar 

  26. Martini L, Fini M, Giavaresi G, Giardino R (2001) Sheep model in orthopedic research: a literature review. Comp Med 51(4):292–299

    PubMed  CAS  Google Scholar 

  27. Newman E, Turner AS, Wark JD (1995) The potential of sheep for the study of osteopenia: current status and comparison with other animal models. Bone 16(4 Suppl):277S–284S

    PubMed  CAS  Google Scholar 

  28. Anderson ML, Dhert WJ, de Bruijn JD, Dalmeijer RA, Leenders H, van Blitterswijk CA et al (1999) Critical size defect in the goat’s os ilium. A model to evaluate bone grafts and substitutes. Clin Orthop Relat Res 364:231–239

    Article  PubMed  Google Scholar 

  29. van der Donk S, Buma P, Aspenberg P, Schreurs BW (2001) Similarity of bone ingrowth in rats and goats: a bone chamber study. Comp Med 51(4):336–340

    PubMed  Google Scholar 

  30. Cancedda R, Giannoni P, Mastrogiacomo M (2007) A tissue engineering approach to bone repair in large animal models and in clinical practice. Biomaterials 28(29):4240–4250

    Article  PubMed  CAS  Google Scholar 

  31. Reichert JC, Epari DR, Wullschleger ME, Saifzadeh S, Steck R, Lienau J et al (2009) Establishment of a preclinical ovine model for tibial segmental bone defect repair by applying bone tissue engineering strategies. Tissue Eng Part B Rev 16(1):93–104

    Article  Google Scholar 

  32. Muschler GF, Raut VP, Patterson TE, Wenke JC, Hollinger JO (2010) The design and use of animal models for translational research in bone tissue engineering and regenerative medicine. Tissue Eng Part B Rev 16(1):123–145

    Article  PubMed  Google Scholar 

  33. Shang Q, Wang Z, Liu W, Shi Y, Cui L, Cao Y (2001) Tissue-engineered bone repair of sheep cranial defects with autologous bone marrow stromal cells. J Craniofac Surg 12(6):586–593, discussion 94–95

    Article  PubMed  CAS  Google Scholar 

  34. Xi Q, Bu RF, Liu HC, Mao TQ (2006) Reconstruction of caprine mandibular segmental defect by tissue engineered bone reinforced by titanium reticulum. Chin J Traumatol 9(2):67–71

    PubMed  CAS  Google Scholar 

  35. Marei MK, Saad MM, El-Ashwah AM, Ei-Backly RM, Al-Khodary MA (2009) Experimental formation of periodontal structure around titanium implants utilizing bone marrow mesenchymal stem cells: a pilot study. J Oral Implantol 35(3):106–129

    Article  PubMed  Google Scholar 

  36. Sauerbier S, Stubbe K, Maglione M, Haberstroh J, Kuschnierz J, Oshima T et al (2010) Mesenchymal stem cells and bovine bone mineral in sinus lift procedures – an experimental study in sheep. Tissue Eng Part C Methods 16(5):1033–1039

    Article  PubMed  CAS  Google Scholar 

  37. Kon E, Muraglia A, Corsi A, Bianco P, Marcacci M, Martin I et al (2000) Autologous bone marrow stromal cells loaded onto porous hydroxyapatite ceramic accelerate bone repair in critical-size defects of sheep long bones. J Biomed Mater Res 49(3):328–337

    Article  PubMed  CAS  Google Scholar 

  38. Bensaid W, Oudina K, Viateau V, Potier E, Bousson V, Blanchat C et al (2005) De novo reconstruction of functional bone by tissue engineering in the metatarsal sheep model. Tissue Eng 11(5-6):814–824

    Article  PubMed  CAS  Google Scholar 

  39. Lucarelli E, Fini M, Beccheroni A, Giavaresi G, Di Bella C, Aldini NN, et al (2005) Stromal stem cells and platelet-rich plasma improve bone allograft integration. Clin Orthop Relat Res 435:62–68

    Google Scholar 

  40. Zhu L, Liu W, Cui L, Cao Y (2006) Tissue-engineered bone repair of goat-femur defects with osteogenically induced bone marrow stromal cells. Tissue Eng 12(3):423–433

    Article  PubMed  CAS  Google Scholar 

  41. Nair MB, Varma HK, Menon KV, Shenoy SJ, John A (2009) Tissue regeneration and repair of goat segmental femur defect with bioactive triphasic ceramic-coated hydroxyapatite scaffold. J Biomed Mater Res A 91(3):855–865

    PubMed  Google Scholar 

  42. Niemeyer P, Schonberger TS, Hahn J, Kasten P, Fellenberg J, Suedkamp N et al (2010) Xenogenic transplantation of human mesenchymal stem cells in a critical size defect of the sheep tibia for bone regeneration. Tissue Eng Part A 16(1):33–43

    Article  PubMed  CAS  Google Scholar 

  43. Niemeyer P, Fechner K, Milz S, Richter W, Suedkamp NP, Mehlhorn AT et al (2010) Comparison of mesenchymal stem cells from bone marrow and adipose tissue for bone regeneration in a critical size defect of the sheep tibia and the influence of platelet-rich plasma. Biomaterials 31(13):3572–3579

    Article  PubMed  CAS  Google Scholar 

  44. Rodrigues MT, Gomes ME, Viegas CA, Azevedo JT, Dias IR, Guzon FM et al (2010) Tissue-engineered constructs based on SPCL scaffolds cultured with goat marrow cells: functionality in femoral defects. J Tissue Eng Regen Med 5(1):41–49

    Article  CAS  Google Scholar 

  45. Feitosa ML, Fadel L, Beltrao-Braga PC, Wenceslau CV, Kerkis I, Kerkis A et al (2010) Successful transplant of mesenchymal stem cells in induced osteonecrosis of the ovine femoral head: preliminary results. Acta Cir Bras 25(5):416–422

    Article  PubMed  Google Scholar 

  46. Boos AM, Loew JS, Deschler G, Arkudas A, Bleiziffer O, Gulle H et al (2011) Directly auto-transplanted mesenchymal stem cells induce bone formation in a ceramic bone substitute in an ectopic sheep model. J Cell Mol Med 15:1364–1378

    Article  PubMed  CAS  Google Scholar 

  47. Guo X, Wang C, Zhang Y, Xia R, Hu M, Duan C et al (2004) Repair of large articular cartilage defects with implants of autologous mesenchymal stem cells seeded into beta-tricalcium phosphate in a sheep model. Tissue Eng 10(11–12):1818–1829

    Article  PubMed  CAS  Google Scholar 

  48. Mrugala D, Bony C, Neves N, Caillot L, Fabre S, Moukoko D et al (2008) Phenotypic and functional characterisation of ovine mesenchymal stem cells: application to a cartilage defect model. Ann Rheum Dis 67(3):288–295

    Article  PubMed  CAS  Google Scholar 

  49. Zscharnack M, Hepp P, Richter R, Aigner T, Schulz R, Somerson J et al (2010) Repair of chronic osteochondral defects using predifferentiated mesenchymal stem cells in an ovine model. Am J Sports Med 38(9):1857–1869

    Article  PubMed  Google Scholar 

  50. Korda M, Blunn G, Goodship A, Hua J (2008) Use of mesenchymal stem cells to enhance bone formation around revision hip replacements. J Orthop Res 26(6):880–885

    Article  PubMed  Google Scholar 

  51. Kandziora F, Pflugmacher R, Scholz M, Schnake K, Lucke M, Schroder R et al (2001) Comparison between sheep and human cervical spines: an anatomic, radiographic, bone mineral density, and biomechanical study. Spine (Phila Pa 1976) 26(9):1028–1037

    Article  CAS  Google Scholar 

  52. Tan KK, Tan GH, Shamsul BS, Chua KH, Ng MH, Ruszymah BH et al (2005) Bone graft substitute using hydroxyapatite scaffold seeded with tissue engineered autologous osteoprogenitor cells in spinal fusion: early result in a sheep model. Med J Malaysia 60(Suppl C):53–58

    PubMed  Google Scholar 

  53. Kruyt MC, Wilson CE, de Bruijn JD, van Blitterswijk CA, Oner CF, Verbout AJ et al (2006) The effect of cell-based bone tissue engineering in a goat transverse process model. Biomaterials 27(29):5099–5106

    Article  PubMed  CAS  Google Scholar 

  54. Goldschlager T, Rosenfeld JV, Young IR, Jenkin G (2009) Anterior cervical discectomy and fusion in the ovine model. J Vis Exp 32:1548

    Google Scholar 

  55. Struillou X, Boutigny H, Soueidan A, Layrolle P (2010) Experimental animal models in periodontology: a review. Open Dent J 4:37–47

    Article  PubMed  Google Scholar 

  56. Jafarian M, Eslaminejad MB, Khojasteh A, Mashhadi Abbas F, Dehghan MM, Hassanizadeh R et al (2008) Marrow-derived mesenchymal stem cells-directed bone ­regeneration in the dog mandible: a comparison between biphasic calcium phosphate and natural bone mineral. Oral Surg Oral Med Oral Pathol Oral Radiol Endod 105(5):e14–e24

    Article  PubMed  Google Scholar 

  57. Ito K, Yamada Y, Naiki T, Ueda M (2006) Simultaneous implant placement and bone regeneration around dental implants using tissue-engineered bone with fibrin glue, mesenchymal stem cells and platelet-rich plasma. Clin Oral Implants Res 17(5):579–586

    Article  PubMed  Google Scholar 

  58. Borenstein N, Chetboul V, Bruneval P, Hekmati M, Tissier R, Behr L et al (2007) ­Non-cultured cell transplantation in an ovine model of non-ischemic heart failure. Eur J Cardiothorac Surg 31(3):444–451

    Article  PubMed  Google Scholar 

  59. Borenstein N, Jian Z, Fromont G, Bruneval P, Hekmati M, Behr L et al (2005) Noncultured cell transplantation in an ovine model of right ventricular preparation. J Thorac Cardiovasc Surg 129(5):1119–1127

    Article  PubMed  Google Scholar 

  60. Gulbins H, Meiser BM, Reichenspurner H, Reichart B (2002) Cell transplantation – a potential therapy for cardiac repair in the future? Heart Surg Forum 5(4):E28–E34

    PubMed  Google Scholar 

  61. Stamm C, Liebold A, Steinhoff G, Strunk D (2006) Stem cell therapy for ischemic heart disease: beginning or end of the road? Cell Transplant 15(Suppl 1):S47–S56

    Article  PubMed  Google Scholar 

  62. Silva GV, Litovsky S, Assad JA, Sousa AL, Martin BJ, Vela D et al (2005) Mesenchymal stem cells differentiate into an endothelial phenotype, enhance vascular density, and improve heart function in a canine chronic ischemia model. Circulation 111(2):150–156

    Article  PubMed  CAS  Google Scholar 

  63. Bartunek J, Croissant JD, Wijns W, Gofflot S, de Lavareille A, Vanderheyden M et al (2007) Pretreatment of adult bone marrow mesenchymal stem cells with cardiomyogenic growth factors and repair of the chronically infarcted myocardium. Am J Physiol Heart Circ Physiol 292(2):H1095–H1104

    Article  PubMed  CAS  Google Scholar 

  64. Mathieu M, Bartunek J, El Oumeiri B, Touihri K, Hadad I, Thoma P et al (2009) Cell therapy with autologous bone marrow mononuclear stem cells is associated with superior cardiac recovery compared with use of nonmodified mesenchymal stem cells in a canine model of chronic myocardial infarction. J Thorac Cardiovasc Surg 138(3):646–653

    Article  PubMed  Google Scholar 

  65. Perin EC, Silva GV, Assad JA, Vela D, Buja LM, Sousa AL et al (2008) Comparison of intracoronary and transendocardial delivery of allogeneic mesenchymal cells in a canine model of acute myocardial infarction. J Mol Cell Cardiol 44(3):486–495

    Article  PubMed  CAS  Google Scholar 

  66. Vincentelli A, Wautot F, Juthier F, Fouquet O, Corseaux D, Marechaux S et al (2007) In vivo autologous recellularization of a tissue-engineered heart valve: are bone marrow mesenchymal stem cells the best candidates? J Thorac Cardiovasc Surg 134(2):424–432

    Article  PubMed  Google Scholar 

  67. Hamamoto H, Gorman JH 3rd, Ryan LP, Hinmon R, Martens TP, Schuster MD et al (2009) Allogeneic mesenchymal precursor cell therapy to limit remodeling after myocardial infarction: the effect of cell dosage. Ann Thorac Surg 87(3):794–801

    Article  PubMed  Google Scholar 

  68. Lim JH, Byeon YE, Ryu HH, Jeong YH, Lee YW, Kim WH et al (2007) Transplantation of canine umbilical cord blood-derived mesenchymal stem cells in experimentally induced spinal cord injured dogs. J Vet Sci 8(3):275–282

    Article  PubMed  Google Scholar 

  69. Ryu HH, Lim JH, Byeon YE, Park JR, Seo MS, Lee YW et al (2009) Functional recovery and neural differentiation after transplantation of allogenic adipose-derived stem cells in a canine model of acute spinal cord injury. J Vet Sci 10(4):273–284

    Article  PubMed  Google Scholar 

  70. Lee JH, Chang HS, Kang EH, Chung DJ, Choi CB, Lee JH et al (2009) Percutaneous transplantation of human umbilical cord blood-derived multipotent stem cells in a canine model of spinal cord injury. J Neurosurg Spine 11(6):749–757

    Article  PubMed  Google Scholar 

  71. Chung DJ, Choi CB, Lee SH, Kang EH, Lee JH, Hwang SH et al (2009) Intraarterially delivered human umbilical cord blood-derived mesenchymal stem cells in canine cerebral ischemia. J Neurosci Res 87(16):3554–3567

    Article  PubMed  CAS  Google Scholar 

  72. Ding F, Wu J, Yang Y, Hu W, Zhu Q, Tang X et al (2010) Use of tissue-engineered nerve grafts consisting of a chitosan/poly(lactic-co-glycolic acid)-based scaffold included with bone marrow mesenchymal cells for bridging 50-mm dog sciatic nerve gaps. Tissue Eng Part A 16(12):3779–3790

    Article  PubMed  CAS  Google Scholar 

  73. Ke H, Wang P, Yu W, Liu X, Liu C, Yang F et al (2009) Derivation, characterization and gene modification of cynomolgus monkey mesenchymal stem cells. Differentiation 77(3):256–262

    Article  PubMed  CAS  Google Scholar 

  74. Bartholomew A, Patil S, Mackay A, Nelson M, Buyaner D, Hardy W et al (2001) Baboon mesenchymal stem cells can be genetically modified to secrete human erythropoietin in vivo. Hum Gene Ther 12(12):1527–1541

    Article  PubMed  CAS  Google Scholar 

  75. King FA, Yarbrough CJ, Anderson DC, Gordon TP, Gould KG (1988) Primates. Science 240(4858):1475–1482

    Article  PubMed  CAS  Google Scholar 

  76. Sibal L, Samson K (2001) Nonhuman primates: a critical role in current disease research. ILAR J 42(2):74–84

    PubMed  CAS  Google Scholar 

  77. van Rood JJ, Claas F (2000) Both self and non-inherited maternal HLA antigens influence the immune response. Immunol Today 21(6):269–273

    Article  PubMed  Google Scholar 

  78. Knechtle SJ, Hamawy MM, Hu H, Fechner JJH, Cho CS (2001) Tolerance and near-tolerance strategies in monkeys and their application to human renal transplantation. Immunol Rev 183(1):205–213

    Article  PubMed  CAS  Google Scholar 

  79. Montgomery SP, Hale DA, Hirshberg B, Harlan DM, Kirk AD (2001) Preclinical evaluation of tolerance induction protocols and islet transplantation in non-human primates. Immunol Rev 183(1):214–222

    Article  PubMed  CAS  Google Scholar 

  80. Wakao S, Hayashi T, Kitada M, Kohama M, Matsue D, Teramoto N et al (2010) Long-term observation of auto-cell transplantation in non-human primate reveals safety and efficiency of bone marrow stromal cell-derived Schwann cells in peripheral nerve regeneration. Exp Neurol 223(2):537–547

    Article  PubMed  CAS  Google Scholar 

  81. Deng YB, Yuan QT, Liu XG, Liu XL, Liu Y, Liu ZG et al (2005) Functional recovery after rhesus monkey spinal cord injury by transplantation of bone marrow mesenchymal-stem cell-derived neurons. Chin Med J (Engl) 118(18):1533–1541

    CAS  Google Scholar 

  82. Isakova IA, Baker K, Dufour J, Gaupp D, Phinney DG (2006) Preclinical evaluation of adult stem cell engraftment and toxicity in the CNS of rhesus macaques. Mol Ther 13(6):1173–1184

    Article  PubMed  CAS  Google Scholar 

  83. Isakova IA, Baker K, DuTreil M, Dufour J, Gaupp D, Phinney DG (2007) Age- and dose-related effects on MSC engraftment levels and anatomical distribution in the central nervous systems of nonhuman primates: identification of novel MSC subpopulations that respond to guidance cues in brain. Stem Cells 25(12):3261–3270

    Article  PubMed  CAS  Google Scholar 

  84. Li J, Zhu H, Liu Y, Li Q, Lu S, Feng M et al (2010) Human mesenchymal stem cell transplantation protects against cerebral ischemic injury and upregulates interleukin-10 expression in Macaca fascicularis. Brain Res 1334:65–72

    Article  PubMed  CAS  Google Scholar 

  85. Behr L, Hekmati M, Fromont G, Borenstein N, Noel LH, Lelievre-Pegorier M et al (2007) Intra renal arterial injection of autologous mesenchymal stem cells in an ovine model in the postischemic kidney. Nephron Physiol 107(3):p65–p76

    Article  PubMed  Google Scholar 

  86. Behr L, Hekmati M, Lucchini A, Houcinet K, Faussat AM, Borenstein N et al (2009) Evaluation of the effect of autologous mesenchymal stem cell injection in a large-animal model of bilateral kidney ischaemia reperfusion injury. Cell Prolif 42(3):284–297

    Article  PubMed  CAS  Google Scholar 

  87. 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(7):1120–1125

    Article  PubMed  CAS  Google Scholar 

  88. Hiyama A, Mochida J, Iwashina T, Omi H, Watanabe T, Serigano K et al (2008) Transplantation of mesenchymal stem cells in a canine disc degeneration model. J Orthop Res 26(5):589–600

    Article  PubMed  CAS  Google Scholar 

  89. Serigano K, Sakai D, Hiyama A, Tamura F, Tanaka M, Mochida J (2010) Effect of cell number on mesenchymal stem cell transplantation in a canine disc degeneration model. J Orthop Res 28(10):1267–1275

    Article  PubMed  Google Scholar 

  90. Flake AW, Hendrick MH, Rice HE, Tavassoli M, Zanjani ED (1995) Enhancement of human hematopoiesis by mast cell growth factor in human-sheep chimeras created by the in utero transplantation of human fetal hematopoietic cells. Exp Hematol 23(3):252–257

    PubMed  CAS  Google Scholar 

  91. Zanjani ED, Almeida-Porada G, Flake AW (1996) The human/sheep xenograft model: a large animal model of human hematopoiesis. Int J Hematol 63(3):179–192

    Article  PubMed  CAS  Google Scholar 

  92. Mackenzie TC, Flake AW (2001) Multilineage differentiation of human MSC after in utero transplantation. Cytotherapy 3(5):403–405

    Article  PubMed  CAS  Google Scholar 

  93. Almeida-Porada G, Zanjani ED (2004) A large animal noninjury model for study of human stem cell plasticity. Blood Cells Mol Dis 32(1):77–81

    Article  PubMed  Google Scholar 

  94. Frias A, Dias IR, Viegas CA, Fernandes S, Barros A, Azevedo JT et al (1995) In vivo ­engraftment potential of human bone marrow and amniotic fluid stem cells cultured under osteogenic condicitons. Tissue Eng 14:746

    Google Scholar 

  95. Shimizu Y, Ogawa M, Kobayashi M, Almeida-Porada G, Zanjani ED (1998) Engraftment of cultured human hematopoietic cells in sheep. Blood 91(10):3688–3692

    PubMed  CAS  Google Scholar 

  96. Almeida-Porada G, Crapnell K, Porada C, Benoit B, Nakauchi H, Quesenberry P et al (2005) In vivo haematopoietic potential of human neural stem cells. Br J Haematol 130(2): 276–283

    Article  PubMed  CAS  Google Scholar 

  97. Almeida-Porada G, Porada C, Gupta N, Torabi A, Thain D, Zanjani ED (2007) The human-sheep chimeras as a model for human stem cell mobilization and evaluation of hematopoietic grafts’ potential. Exp Hematol 35(10):1594–1600

    Article  PubMed  CAS  Google Scholar 

  98. Almeida-Porada G, Porada CD, Chamberlain J, Torabi A, Zanjani ED (2004) Formation of human hepatocytes by human hematopoietic stem cells in sheep. Blood 104(8):2582–2590

    Article  PubMed  CAS  Google Scholar 

  99. Troeger C, Surbek D, Schoberlein A, Schatt S, Dudler L, Hahn S et al (2007) In utero haematopoietic stem cell transplantation. Experiences in mice, sheep and humans. Swiss Med Wkly 137(Suppl 155):14S–19S

    PubMed  Google Scholar 

  100. Almeida-Porada G, Porada CD, Tran N, Zanjani ED (2000) Cotransplantation of human stromal cell progenitors into preimmune fetal sheep results in early appearance of human donor cells in circulation and boosts cell levels in bone marrow at later time points after transplantation. Blood 95(11):3620–3627

    PubMed  CAS  Google Scholar 

  101. McNiece IK, Almeida-Porada G, Shpall EJ, Zanjani E (2002) Ex vivo expanded cord blood cells provide rapid engraftment in fetal sheep but lack long-term engrafting potential. Exp Hematol 30(6):612–616

    Article  PubMed  Google Scholar 

  102. Huang L, Wong YP, Gu H, Cai YJ, Ho Y, Wang CC et al (2010) Stem cell-like properties of human umbilical cord lining epithelial cells and the potential for epidermal reconstitution. Cytotherapy 13(2):145–155

    Article  PubMed  CAS  Google Scholar 

  103. Chamberlain J, Yamagami T, Colletti E, Theise ND, Desai J, Frias A et al (2007) Efficient generation of human hepatocytes by the intrahepatic delivery of clonal human mesenchymal stem cells in fetal sheep. Hepatology 46(6):1935–1945

    Article  PubMed  CAS  Google Scholar 

  104. Airey JA, Almeida-Porada G, Colletti EJ, Porada CD, Chamberlain J, Movsesian M et al (2004) Human mesenchymal stem cells form Purkinje fibers in fetal sheep heart. Circulation 109(11):1401–1407

    Article  PubMed  Google Scholar 

  105. Colletti EJ, Airey JA, Liu W, Simmons PJ, Zanjani ED, Porada CD et al (2009) Generation of tissue-specific cells from MSC does not require fusion or donor-to-host mitochondrial/membrane transfer. Stem Cell Res 2(2):125–138

    Article  PubMed  Google Scholar 

  106. Ersek A, Pixley JS, Goodrich AD, Porada CD, Almeida-Porada G, Thain DS et al (2010) Persistent circulating human insulin in sheep transplanted in utero with human mesenchymal stem cells. Exp Hematol 38(4):311–320

    Article  PubMed  CAS  Google Scholar 

  107. Devine SM, Bartholomew AM, Mahmud N, Nelson M, Patil S, Hardy W et al (2001) Mesenchymal stem cells are capable of homing to the bone marrow of non-human primates following systemic infusion. Exp Hematol 29(2):244–255

    Article  PubMed  CAS  Google Scholar 

  108. Devine SM, Cobbs C, Jennings M, Bartholomew A, Hoffman R (2003) Mesenchymal stem cells distribute to a wide range of tissues following systemic infusion into nonhuman primates. Blood 101(8):2999–3001

    Article  PubMed  CAS  Google Scholar 

  109. Mahmud N, Pang W, Cobbs C, Alur P, Borneman J, Dodds R et al (2004) Studies of the route of administration and role of conditioning with radiation on unrelated allogeneic mismatched mesenchymal stem cell engraftment in a nonhuman primate model. Exp Hematol 32(5):494–501

    Article  PubMed  CAS  Google Scholar 

  110. Beggs KJ, Lyubimov A, Borneman JN, Bartholomew A, Moseley A, Dodds R et al (2006) Immunologic consequences of multiple, high-dose administration of allogeneic mesenchymal stem cells to baboons. Cell Transplant 15(8–9):711–721

    Article  PubMed  Google Scholar 

  111. Bartholomew A, Sturgeon C, Siatskas M, Ferrer K, McIntosh K, Patil S et al (2002) Mesenchymal stem cells suppress lymphocyte proliferation in vitro and prolong skin graft survival in vivo. Exp Hematol 30(1):42–48

    Article  PubMed  Google Scholar 

  112. Berman DM, Willman MA, Han D, Kleiner G, Kenyon NM, Cabrera O et al (2010) Mesenchymal stem cells enhance allogeneic islet engraftment in nonhuman primates. Diabetes 59(10):2558–2568

    Article  PubMed  CAS  Google Scholar 

  113. Chapel A, Bertho JM, Bensidhoum M, Fouillard L, Young RG, Frick J et al (2003) Mesenchymal stem cells home to injured tissues when co-infused with hematopoietic cells to treat a radiation-induced multi-organ failure syndrome. J Gene Med 5(12):1028–1038

    Article  PubMed  Google Scholar 

  114. Masuda S, Ageyama N, Shibata H, Obara Y, Ikeda T, Takeuchi K et al (2009) Cotransplantation with MSCs improves engraftment of HSCs after autologous intra-bone marrow transplantation in nonhuman primates. Exp Hematol 37(10):1250–1257 e1

    Article  PubMed  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Division of Regenerative Medicine, Tulane National Primate Research Center, Tulane University School of Medicine, New Orleans, LA, USA

    Bruce A. Bunnell Ph.D.

  2. Division of Regenerative Medicine, Tulane National Primate Research Center, New Orleans, LA, USA

    Bruce A. Bunnell Ph.D. & Christine Gagliardi

  3. Department of Pharmacology, Tulane University School of Medicine, New Orleans, LA, USA

    Bruce A. Bunnell Ph.D. & Christine Gagliardi

  4. Department of Veterinary Sciences, School of Agrarian and Veterinary Sciences, University of Trás-os-Montes e Alto Douro, Vila Real, Portugal

    Maria Isabel Ribeiro Dias

Authors
  1. Bruce A. Bunnell Ph.D.
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Christine Gagliardi
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Maria Isabel Ribeiro Dias
    View author publications

    You can also search for this author in PubMed Google Scholar

Editor information

Editors and Affiliations

  1. Madison School of Medicine and Public He, Department of Medicine, Hematology/Oncol, University of Wisconsin, 1111 Highland Avenue MC2275, Madison, 53705, USA

    Peiman Hematti

  2. Princess Margaret Hospital, Cell Therapy Program, University of Toronto, University Avenue 610, Toronto, M5G 2M9, Ontario, Canada

    Armand Keating

Rights and permissions

Reprints and permissions

Copyright information

© 2013 Springer Science+Business Media New York

About this chapter

Cite this chapter

Bunnell, B.A., Gagliardi, C., Dias, M.I.R. (2013). MSC Studies in Large-Animal Models. In: Hematti, P., Keating, A. (eds) Mesenchymal Stromal Cells. Stem Cell Biology and Regenerative Medicine. Humana Press, New York, NY. https://doi.org/10.1007/978-1-4614-5711-4_13

Download citation

Publish with us

Policies and ethics

Search

Navigation