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Cytotechnology

, Volume 59, Issue 1, pp 55–64 | Cite as

Human mesenchymal stem cells implantation into the degenerated coccygeal disc of the rat

  • Je Hoon Jeong
  • Eun Sun Jin
  • Joong Kee Min
  • Sang Ryong Jeon
  • Chan-Sik Park
  • Hyun Soo Kim
  • Kyoung Hyo ChoiEmail author
Original Research

Abstract

In this study, the authors explored the effect of human mesenchymal stem cell (MSC) implantation on the restoration of degenerative intervertebral discs (IVDs) in the rat. A unique rat coccygeal model was used to investigate the effects of transplanting human MSCs and to examine MSC survival in degenerative discs. MSC implantations into rat coccygeal IVDs were performed at 2 weeks post-injury. Radiologic and histologic evaluations were performed at 2, 4, 6, and 8 weeks post-injury. MSC-injected segments (TS) retained disc height and signal intensity, but injured non-injected segment (IS) progressively lost disc height. Pathological results revealed that the TS group showed relative restoration of the inner annulus structure; however, the IS group showed destruction of the inner annulus structure. Immunohistochemical staining using Anti-Human Nucleic Antibody (#MAB1281 Chemicon) revealed positive staining in the TS group at 2 weeks post-transplantation (4 weeks post-injury). This study shows that human MSCs survive for 2 weeks after transplantation into the IVDs of rats, and that MSCs increased the heights and signal intensities of intervertebral disc.

Keywords

Mesenchymal stem cell Animal model Intervertebral Disc Degeneration 

Notes

Acknowledgments

Financial support was provided by a grant from the Asan institude for life science

References

  1. An HS, Takegami K, Kamada H, Nguyen CM, Thonar EJ, Singh K, Andersson GB, Masuda K (2005) Intradiscal administration of osteogenic protein-1 increases intervertebral disc height and proteoglycan content in the nucleus pulposus in normal adolescent rabbits. Spine 30:25–31 (discussion 31–22)Google Scholar
  2. Antoniou J, Steffen T, Nelson F, Winterbottom N, Hollander AP, Poole RA, Aebi M, Alini M (1996) The human lumbar intervertebral disc: evidence for changes in the biosynthesis and denaturation of the extracellular matrix with growth, maturation, ageing, and degeneration. J Clin Invest 98:996–1003. doi: 10.1172/JCI118884 CrossRefGoogle Scholar
  3. Bang OY, Lee JS, Lee PH, Lee G (2005) Autologous mesenchymal stem cell transplantation in stroke patients. Ann Neurol 57:874–882. doi: 10.1002/ana.20501 CrossRefGoogle Scholar
  4. Barry FP (2003) Biology and clinical applications of mesenchymal stem cells. Birth Defects Res C Embryo Today 69:250–256. doi: 10.1002/bdrc.10021 CrossRefGoogle Scholar
  5. Bjorklund A, Lindvall O (2000) Cell replacement therapies for central nervous system disorders. Nat Neurosci 3:537–544. doi: 10.1038/75705 CrossRefGoogle Scholar
  6. Chen X, Katakowski M, Li Y et al (2002) Human bone marrow stromal cell cultures conditioned by traumatic brain tissue extracts: growth factor production. J Neurosci Res 69:687–691. doi: 10.1002/jnr.10334 CrossRefGoogle Scholar
  7. Cheung KMC, Ho G, Leung VYL, Chan D (2005) The effect of severity of disc degeneration on mesenchymal stem cells’ ability to regenerate the intervertebral disc: a rabbit model. Eur Cell Mater (Suppl 3): 45Google Scholar
  8. Chopp M, Li Y (2002) Treatment of neural injury with marrow stromal cells. Lancet Neurol 1:92–100. doi: 10.1016/S1474-4422(02)00040-6 CrossRefGoogle Scholar
  9. Cizkova D, Rosocha J, Vanicky I, Jergova S, Cizek M (2006) Transplants of human mesenchymal stem cells improve functional recovery after spinal cord injury in the rat. Cell Mol Neurobiol 26:1167–1180. doi: 10.1007/s10571-006-9093-1 CrossRefGoogle Scholar
  10. Crevensten G, Walsh AJ, Ananthakrishnan D, Page P, Wahba GM, Lotz JC, Berven S (2004) Intervertebral disc cell therapy for regeneration: mesenchymal stem cell implantation in rat intervertebral discs. Ann Biomed Eng 32:430–434. doi: 10.1023/B:ABME.0000017545.84833.7c CrossRefGoogle Scholar
  11. Deans RJ, Moseley AB (2000) Mesenchymal stem cells: biology and potential clinical uses. Exp Hematol 28:875–884. doi: 10.1016/S0301-472X(00)00482-3 CrossRefGoogle Scholar
  12. Ganey T, Libera J, Moos V, Alasevic O, Fritsch KG, Meisel HJ, Hutton WC (2003) Disc chondrocyte transplantation in a canine model: a treatment for degenerated or damaged intervertebral disc. Spine 28:2609–2620. doi: 10.1097/01.BRS.0000097891.63063.78 CrossRefGoogle Scholar
  13. Gimble J, Guilak F (2003) Adipose-derived adult stem cells: isolation, characterization, and differentiation potential. Cytotherapy 5:362–369. doi: 10.1080/14653240310003026 CrossRefGoogle Scholar
  14. Gruber HE, Johnson TL, Leslie K et al (2002) Autologous intervertebral disc cell implantation: a model using Psammomys obesus, the sand rat. Spine 27:1626–1633. doi: 10.1097/00007632-200208010-00007 CrossRefGoogle Scholar
  15. Horwitz EM, Prockop DJ, Fitzpatrick LA et al (1999) Transplantability and therapeutic effects of bone marrow-derived mesenchymal cells in children with osteogenesis imperfecta. Nat Med 5:309–313. doi: 10.1038/6529 CrossRefGoogle Scholar
  16. Im GI, Kim DY, Shin JH, Hyun C, Cho WH (2001) Repair of cartilage defect in the rabbit with cultured mesenchymal stem cells from bone marrow. J Bone Jt Surg Br 83:289–294. doi: 10.1302/0301-620X.83B2.10495 CrossRefGoogle Scholar
  17. Jendelova P, Herynek V, Urdzikova L et al (2004) Magnetic resonance tracking of transplanted bone marrow and embryonic stem cells labeled by iron oxide nanoparticles in rat brain and spinal cord. J Neurosci Res 76:232–243. doi: 10.1002/jnr.20041 CrossRefGoogle Scholar
  18. Jiang Y, Jahagirdar BN, Reinhardt RL et al (2002) Pluripotency of mesenchymal stem cells derived from adult marrow. Nature 418:41–49. doi: 10.1038/nature00870 CrossRefGoogle Scholar
  19. Kawakami M, Matsumoto T, Hashizume H, Kuribayashi K, Chubinskaya S, Yoshida M (2005) Osteogenic protein-1 (osteogenic protein-1/bone morphogenetic protein-7) inhibits degeneration and pain-related behavior induced by chronically compressed nucleus pulposus in the rat. Spine 30:1933–1939. doi: 10.1097/01.brs.0000176319.78887.64 CrossRefGoogle Scholar
  20. Kraemer J (1995) Natural course and prognosis of intervertebral disc diseases. International society for the study of the lumbar spine Seattle, Washington, June 1994. Spine 20:635–639. doi: 10.1097/00007632-199503150-00001 CrossRefGoogle Scholar
  21. Le Visage C, Kim SW, Tateno K, Sieber AN, Kostuik JP, Leong KW (2006) Interaction of human mesenchymal stem cells with disc cells: changes in extracellular matrix biosynthesis. Spine 31:2036–2042. doi: 10.1097/01.brs.0000231442.05245.87 CrossRefGoogle Scholar
  22. Leung VY, Chan D, Cheung KM (2006) Regeneration of intervertebral disc by mesenchymal stem cells: potentials, limitations, and future direction. Eur Spine J 15(Suppl 3):S406–S413. doi: 10.1007/s00586-006-0183-z CrossRefGoogle Scholar
  23. Li Y, Chen J, Chen XG et al (2002) Human marrow stromal cell therapy for stroke in rat: neurotrophins and functional recovery. Neurology 59:514–523Google Scholar
  24. Li WY, Choi YJ, Lee PH et al (2008) Mesenchymal stem cells for ischemic stroke: changes in effects after ex vivo culturing. Cell Transplant 17:1045–1059. doi: 10.3727/096368908786991551 CrossRefGoogle Scholar
  25. Liechty KW, Mackenzie TC, Shaaban AF, Radu A, Moseley AM, Deans R, Marshak DR, Flake AW (2000) Human mesenchymal stem cells engraft and demonstrate site-specific differentiation after in utero transplantation in sheep. Nat Med 6:1282–1286. doi: 10.1038/81395 CrossRefGoogle Scholar
  26. Lu DS, Shono Y, Oda I, Abumi K, Kaneda K (1997) Effects of chondroitinase ABC and chymopapain on spinal motion segment biomechanics. An in vivo biomechanical, radiologic, and histologic canine study. Spine 22:1828–1834. doi: 10.1097/00007632-199708150-00006 (discussion 1834–1825)CrossRefGoogle Scholar
  27. Mahmood A, Lu D, Chopp M (2004) Intravenous administration of marrow stromal cells (MSCs) increases the expression of growth factors in rat brain after traumatic brain injury. J Neurotrauma 21:33–39. doi: 10.1089/089771504772695922 CrossRefGoogle Scholar
  28. Martin MD, Boxell CM, Malone DG (2002) Pathophysiology of lumbar disc degeneration: a review of the literature. Neurosurg Focus 13:E1. doi: 10.3171/foc.2002.13.2.2 CrossRefGoogle Scholar
  29. Nishida K, Kang JD, Gilbertson LG, Moon SH, Suh JK, Vogt MT, Robbins PD, Evans CH (1999) Modulation of the biologic activity of the rabbit intervertebral disc by gene therapy: an in vivo study of adenovirus-mediated transfer of the human transforming growth factor beta 1 encoding gene. Spine 24:2419–2425. doi: 10.1097/00007632-199912010-00002 CrossRefGoogle Scholar
  30. Nishimura K, Mochida J (1998) Percutaneous reinsertion of the nucleus pulposus. An experimental study. Spine 23:1531–1538. doi: 10.1097/00007632-199807150-00006 (discussion 1539)CrossRefGoogle Scholar
  31. Nomura T, Mochida J, Okuma M, Nishimura K, Sakabe K (2001) Nucleus pulposus allograft retards intervertebral disc degeneration. Clin Orthop Relat Res 389:94–101. doi: 10.1097/00003086-200108000-00015 CrossRefGoogle Scholar
  32. Okano H (2002) Stem cell biology of the central nervous system. J Neurosci Res 69:698–707. doi: 10.1002/jnr.10343 CrossRefGoogle Scholar
  33. Okuma M, Mochida J, Nishimura K, Sakabe K, Seiki K (2000) Reinsertion of stimulated nucleus pulposus cells retards intervertebral disc degeneration: an in vitro and in vivo experimental study. J Orthop Res 18:988–997. doi: 10.1002/jor.1100180620 CrossRefGoogle Scholar
  34. Paul R, Haydon RC, Cheng H et al (2003) Potential use of Sox9 gene therapy for intervertebral degenerative disc disease. Spine 28:755–763. doi: 10.1097/00007632-200304150-00006 CrossRefGoogle Scholar
  35. Preston SL, Alison MR, Forbes SJ, Direkze NC, Poulsom R, Wright NA (2003) The new stem cell biology: something for everyone. Mol Pathol 56:86–96. doi: 10.1136/mp.56.2.86 CrossRefGoogle Scholar
  36. Prockop DJ (1997) Marrow stromal cells as stem cells for nonhematopoietic tissues. Science 276:71–74. doi: 10.1126/science.276.5309.71 CrossRefGoogle Scholar
  37. Quintavalla J, Uziel-Fusi S, Yin J et al (2002) Fluorescently labeled mesenchymal stem cells (MSCs) maintain multilineage potential and can be detected following implantation into articular cartilage defects. Biomaterials 23:109–119. doi: 10.1016/S0142-9612(01)00086-2 CrossRefGoogle Scholar
  38. Risbud MV, Albert TJ, Guttapalli A, Vresilovic EJ, Hillibrand AS, Vaccaro AR, Shapiro IM (2004) Differentiation of mesenchymal stem cells towards a nucleus pulposus-like phenotype in vitro: implications for cell-based transplantation therapy. Spine 29:2627–2632. doi: 10.1097/01.brs.0000146462.92171.7f CrossRefGoogle Scholar
  39. Rousseau MA, Ulrich JA, Bass EC, Rodriguez AG, Liu JJ, Lotz JC (2007) Stab incision for inducing intervertebral disc degeneration in the rat. Spine 32:17–24. doi: 10.1097/01.brs.0000251013.07656.45 CrossRefGoogle Scholar
  40. Sakai D, Mochida J, Yamamoto Y et al (2003) Transplantation of mesenchymal stem cells embedded in Atelocollagen gel to the intervertebral disc: a potential therapeutic model for disc degeneration. Biomaterials 24:3531–3541. doi: 10.1016/S0142-9612(03)00222-9 CrossRefGoogle Scholar
  41. Sakai D, Mochida J, Iwashina T, Watanabe T, Nakai T, Ando K, Hotta T (2005) Differentiation of mesenchymal stem cells transplanted to a rabbit degenerative disc model: potential and limitations for stem cell therapy in disc regeneration. Spine 30:2379–2387. doi: 10.1097/01.brs.0000184365.28481.e3 CrossRefGoogle Scholar
  42. Sakai D, Mochida J, Iwashina T et al (2006) Regenerative effects of transplanting mesenchymal stem cells embedded in atelocollagen to the degenerated intervertebral disc. Biomaterials 27:335–345. doi: 10.1016/j.biomaterials.2005.06.038 CrossRefGoogle Scholar
  43. Steck E, Bertram H, Abel R, Chen B, Winter A, Richter W (2005) Induction of intervertebral disc-like cells from adult mesenchymal stem cells. Stem Cells 23:403–411. doi: 10.1634/stemcells.2004-0107 CrossRefGoogle Scholar
  44. Takegami K, An HS, Kumano F, Chiba K, Thonar EJ, Singh K, Masuda K (2005) Osteogenic protein-1 is most effective in stimulating nucleus pulposus and annulus fibrosus cells to repair their matrix after chondroitinase ABC-induced in vitro chemonucleolysis. Spine J 5:231–238. doi: 10.1016/j.spinee.2004.11.001 CrossRefGoogle Scholar
  45. Toma C, Pittenger MF, Cahill KS, Byrne BJ, Kessler PD (2002) Human mesenchymal stem cells differentiate to a cardiomyocyte phenotype in the adult murine heart. Circulation 105:93–98. doi: 10.1161/hc0102.101442 CrossRefGoogle Scholar
  46. Wakitani S, Goto T, Pineda SJ, Young RG, Mansour JM, Caplan AI, Goldberg VM (1994) Mesenchymal cell-based repair of large, full-thickness defects of articular cartilage. J Bone Jt Surg Am 76:579–592Google Scholar
  47. Wallach CJ, Sobajima S, Watanabe Y, Kim JS, Georgescu HI, Robbins P, Gilbertson LG, Kang JD (2003) Gene transfer of the catabolic inhibitor TIMP-1 increases measured proteoglycans in cells from degenerated human intervertebral discs. Spine 28:2331–2337. doi: 10.1097/01.BRS.0000085303.67942.94 CrossRefGoogle Scholar
  48. Yoon ST, Park JS, Kim KS, Li J, Attallah-Wasif ES, Hutton WC, Boden SD (2004) ISSLS prize winner: LMP-1 upregulates intervertebral disc cell production of proteoglycans and BMPs in vitro and in vivo. Spine 29:2603–2611. doi: 10.1097/01.brs.0000146103.94600.85 CrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media B.V. 2009

Authors and Affiliations

  • Je Hoon Jeong
    • 1
    • 2
  • Eun Sun Jin
    • 2
  • Joong Kee Min
    • 2
  • Sang Ryong Jeon
    • 2
  • Chan-Sik Park
    • 2
  • Hyun Soo Kim
    • 3
  • Kyoung Hyo Choi
    • 2
    • 4
    Email author
  1. 1.Department of Neurological Surgery, Hangang Sacred Heart Hospital, College of MedicineHallym UniversitySeoulKorea
  2. 2.Laboratory of Stem Cell Therapy, College of Medicine, Asan Medical CenterUniversity of UlsanSeoulKorea
  3. 3.FCB-PharmicellSungnam-siSouth Korea
  4. 4.Department of Rehabilitation Medicine, Asan Medical Center, College of MedicineUniversity of UlsanSongpa-gu, SeoulKorea

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