Characterization of in vivo effects of platelet-rich plasma and biodegradable gelatin hydrogel microspheres on degenerated intervertebral discs.

We have previously shown that administration of platelet-rich plasma-impregnated gelatin hydrogel microspheres (PRP-GHMs) into a degenerated intervertebral disc (IVD) markedly suppresses progression of IVD degeneration. In the current study, we characterized the in vivo effects of PRP-GHM treatment in a degenerated IVD model in rabbit. On magnetic resonance images, the IVD height was significantly greater after treatment with PRP-GHMs compared with phosphate-buffered saline-impregnated GHMs, PRP without GHMs, and needle puncture only. Water content was also preserved in PRP-GHM-treated IVDs. Consistent with this observation, the mRNA expression of proteoglycan core protein and type II collagen was significantly higher after PRP-GHM treatment compared with other treatment groups. No proliferating cells were found in the nucleus pulposus and inner annulus fibrosus in any groups, but the number of apoptotic cells in the nucleus pulposus after PRP-GHM treatment was significantly lower than that after other treatments. These results provide an improved understanding of the therapeutic effects of PRP-GHM treatment of degenerated IVDs.

[1]  K. Fung,et al.  Evaluation of postoperative drainage with application of platelet‐rich and platelet‐poor plasma following hemithyroidectomy: A randomized controlled clinical trial , 2008, Head & neck.

[2]  M. Finkelstein,et al.  Platelet‐Rich Plasma for Pediatric Tonsillectomy Patients , 2008, The Laryngoscope.

[3]  T. Kubo,et al.  Induction of chondrogenic phenotype in synovium-derived progenitor cells by intermittent hydrostatic pressure. , 2008, Osteoarthritis and cartilage.

[4]  H. Brisby,et al.  Bone morphogenetic protein-7 protects human intervertebral disc cells in vitro from apoptosis. , 2008, The spine journal : official journal of the North American Spine Society.

[5]  Y. Tabata,et al.  Controlled release of platelet growth factors enhances bone regeneration at rabbit calvaria. , 2007, Oral surgery, oral medicine, oral pathology, oral radiology, and endodontics.

[6]  Y. Tabata,et al.  The regenerative effects of platelet-rich plasma on meniscal cells in vitro and its in vivo application with biodegradable gelatin hydrogel. , 2007, Tissue engineering.

[7]  J. Alió,et al.  Symptomatic Dry Eye Treatment with Autologous Platelet-Rich Plasma , 2007, Ophthalmic Research.

[8]  Iñigo Mujika,et al.  Comparison of Surgically Repaired Achilles Tendon Tears Using Platelet-Rich Fibrin Matrices , 2007, The American journal of sports medicine.

[9]  T. Kubo,et al.  Intervertebral disc regeneration using platelet-rich plasma and biodegradable gelatin hydrogel microspheres. , 2007, Tissue engineering.

[10]  C. Su,et al.  Tissue‐engineered intervertebral disc and chondrogenesis using human nucleus pulposus regulated through TGF‐β1 in platelet‐rich plasma , 2006, Journal of cellular physiology.

[11]  G. Andersson,et al.  Effects of Growth Differentiation Factor-5 on the Intervertebral Disc−In Vitro Bovine Study and In Vivo Rabbit Disc Degeneration Model Study , 2006, Spine.

[12]  M Attawia,et al.  Platelet-rich plasma stimulates porcine articular chondrocyte proliferation and matrix biosynthesis. , 2006, Osteoarthritis and cartilage.

[13]  D. Ruan,et al.  Effects of TGF-β1 and IGF-1 on proliferation of human nucleus pulposus cells in medium with different serum concentrations , 2006, Journal of orthopaedic surgery and research.

[14]  N. Boos,et al.  The Course of Macroscopic Degeneration in the Human Lumbar Intervertebral Disc , 2006, Spine.

[15]  J. Leong,et al.  Cervical Intervertebral Disc Degeneration Induced by Unbalanced Dynamic and Static Forces: A Novel In Vivo Rat Model , 2006, Spine.

[16]  Achim Elfering,et al.  Effect of aging and degeneration on disc volume and shape: A quantitative study in asymptomatic volunteers , 2006, Journal of orthopaedic research : official publication of the Orthopaedic Research Society.

[17]  E. Thonar,et al.  Platelet-Rich Plasma (PRP) Stimulates the Extracellular Matrix Metabolism of Porcine Nucleus Pulposus and Anulus Fibrosus Cells Cultured in Alginate Beads , 2006, Spine.

[18]  E. Thonar,et al.  Osteogenic Protein-1 Injection Into a Degenerated Disc Induces the Restoration of Disc Height and Structural Changes in the Rabbit Anular Puncture Model , 2006, Spine.

[19]  Xiaobing Fu,et al.  Possible Pathogenesis of Painful Intervertebral Disc Degeneration , 2006, Spine.

[20]  Y. Tabata,et al.  Augmented bone regeneration activity of platelet-rich plasma by biodegradable gelatin hydrogel. , 2005, Tissue engineering.

[21]  K. Ha,et al.  An Autocrine or Paracrine Fas-Mediated Counterattack: A Potential Mechanism for Apoptosis of Notochordal Cells in Intact Rat Nucleus Pulposus , 2005, Spine.

[22]  E. Thonar,et al.  Intradiscal Administration of Osteogenic Protein-1 Increases Intervertebral Disc Height and Proteoglycan Content in the Nucleus Pulposus in Normal Adolescent Rabbits , 2005, Spine.

[23]  W. Hutton,et al.  ISSLS Prize Winner: LMP-1 Upregulates Intervertebral Disc Cell Production of Proteoglycans and BMPs In Vitro and In Vivo , 2004, Spine.

[24]  P. Roughley.  Biology of Intervertebral Disc Aging and Degeneration: Involvement of the Extracellular Matrix , 2004, Spine.

[25]  B. Eppley,et al.  Platelet quantification and growth factor analysis from platelet-rich plasma: implications for wound healing. , 2004, Plastic and reconstructive surgery.

[26]  S. Nishimoto,et al.  Efficacy of platelet-rich plasma in alveolar bone grafting. , 2004, Journal of oral and maxillofacial surgery : official journal of the American Association of Oral and Maxillofacial Surgeons.

[27]  Ziv Mazor,et al.  Platelet-Rich Plasma for Bone Graft Enhancement in Sinus Floor Augmentation With Simultaneous Implant Placement: Patient Series Study , 2004, Implant dentistry.

[28]  J. Lotz,et al.  In Vivo Growth Factor Treatment of Degenerated Intervertebral Discs , 2004, Spine.

[29]  E. Thonar,et al.  Recombinant osteogenic protein‐1 upregulates extracellular matrix metabolism by rabbit annulus fibrosus and nucleus pulposus cells cultured in alginate beads , 2003, Journal of orthopaedic research : official publication of the Orthopaedic Research Society.

[30]  T. Kawase,et al.  Platelet-rich plasma contains high levels of platelet-derived growth factor and transforming growth factor-beta and modulates the proliferation of periodontally related cells in vitro. , 2003, Journal of periodontology.

[31]  C. Pfirrmann,et al.  Magnetic Resonance Classification of Lumbar Intervertebral Disc Degeneration , 2001, Spine.

[32]  J. Mochida,et al.  Nucleus Pulposus Allograft Retards Intervertebral Disc Degeneration , 2001, Clinical orthopaedics and related research.

[33]  H. Gruber,et al.  Anti-Apoptotic Effects of IGF-1 and PDGF on Human Intervertebral Disc Cells In Vitro , 2000, Spine.

[34]  A. Gray,et al.  The economic burden of back pain in the UK , 1999, Pain.

[35]  Y. Ikada,et al.  Biodegradation of hydrogel carrier incorporating fibroblast growth factor. , 1999, Tissue engineering.

[36]  M Feuerstein,et al.  Health Care and Indemnity Costs Across the Natural History of Disability in Occupational Low Back Pain , 1998, Spine.

[37]  J. Mochida,et al.  Percutaneous Reinsertion of the Nucleus Pulposus: An Experimental Study , 1998, Spine.

[38]  Ikada,et al.  Protein release from gelatin matrices. , 1998, Advanced drug delivery reviews.

[39]  H E Gruber,et al.  Human intervertebral disc cells from the annulus: three-dimensional culture in agarose or alginate and responsiveness to TGF-beta1. , 1997, Experimental cell research.

[40]  M. Jayson,et al.  Nerve ingrowth into diseased intervertebral disc in chronic back pain , 1997, The Lancet.

[41]  J. P. Thompson,et al.  Stimulation of Mature Canine Intervertebral Disc by Growth Factors , 1991, Spine.

[42]  V. Dabbs,et al.  Correlation between disc height narrowing and low-back pain. , 1990, Spine.

[43]  D. Lane,et al.  Monoclonal antibody analysis of the proliferating cell nuclear antigen (PCNA). Structural conservation and the detection of a nucleolar form. , 1990, Journal of cell science.

[44]  R. Soames,et al.  Human intervertebral disc: Structure and function , 1988, The Anatomical record.

[45]  J A Buckwalter,et al.  Ultrastructure of the human intervertebral disc: II. Cells of the nucleus pulposus , 1982, The Anatomical record.

[46]  Yasuhiko Tabata,et al.  The therapeutic effects of basic fibroblast growth factor contained in gelatin hydrogel microspheres on experimental osteoarthritis in the rabbit knee. , 2006, Arthritis and rheumatism.

[47]  James D. Kang,et al.  Quantitative analysis of gene expression in a rabbit model of intervertebral disc degeneration by real-time polymerase chain reaction. , 2005, The spine journal : official journal of the North American Spine Society.

[48]  Yasuhiko Tabata,et al.  Tissue regeneration based on growth factor release. , 2003, Tissue engineering.

[49]  Y Ikada,et al.  Neovascularization effect of biodegradable gelatin microspheres incorporating basic fibroblast growth factor. , 1999, Journal of biomaterials science. Polymer edition.

[50]  Y. Ikada,et al.  Ectopic bone formation induced by biodegradable hydrogels incorporating bone morphogenetic protein. , 1998, Journal of biomaterials science. Polymer edition.

[51]  J. Urban,et al.  Swelling pressure of the inervertebral disc: influence of proteoglycan and collagen contents. , 1985, Biorheology.

[52]  J A Buckwalter,et al.  Ultrastructure of the human intervertebral disc. I. Changes in notochordal cells with age. , 1982, Tissue & cell.

[53]  H. Muir,et al.  Experimental intervertebral disc degeneration: morphologic and proteoglycan changes over time. , 1981, Arthritis and rheumatism.