FREE SHIPPING over $40
OVER 9000 FIVE-STAR REVIEWS
5% OFF ALL SUBSCRIPTIONS
100% HAPPINESS GUARANTEE
Analyze Diet
0
Home / Equine Research Bank / J Bone Joint Surg Br / Genetic modification of chondrocytes with insulin-like growt...
The Journal of bone and joint surgery. British volume2007; 89(5); 672-685; doi: 10.1302/0301-620X.89B5.18343

Genetic modification of chondrocytes with insulin-like growth factor-1 enhances cartilage healing in an equine model.

Abstract: Gene therapy with insulin-like growth factor-1 (IGF-1) increases matrix production and enhances chondrocyte proliferation and survival in vitro. The purpose of this study was to determine whether arthroscopically-grafted chondrocytes genetically modified by an adenovirus vector encoding equine IGF-1 (AdIGF-1) would have a beneficial effect on cartilage healing in an equine femoropatellar joint model. A total of 16 horses underwent arthroscopic repair of a single 15 mm cartilage defect in each femoropatellar joint. One joint received 2 x 10(7) AdIGF-1 modified chondrocytes and the contralateral joint received 2 x 10(7) naive (unmodified) chondrocytes. Repairs were analysed at four weeks, nine weeks and eight months after surgery. Morphological and histological appearance, IGF-1 and collagen type II gene expression (polymerase chain reaction, in situ hybridisation and immunohistochemistry), collagen type II content (cyanogen bromide and sodium dodecyl sulphate-polyacrylamide gel electrophoresis), proteoglycan content (dimethylmethylene blue assay), and gene expression for collagen type I, matrix metalloproteinase (MMP)-1, MMP-3, MMP-13, aggrecanase-1, tissue inhibitor of matrix metalloproteinase-1 (TIMP-1) and TIMP-3 were evaluated. Genetic modification of chondrocytes significantly increased IGF-1 mRNA and ligand production in repair tissue for up to nine weeks following transplantation. The gross and histological appearance of IGF-1 modified repair tissue was improved over control defects. Gross filling of defects was significantly improved at four weeks, and a more hyaline-like tissue covered the lesions at eight months. Histological outcome at four and nine weeks post-transplantation revealed greater tissue filling of defects transplanted with genetically modified chondrocytes, whereas repair tissue in control defects was thin and irregular and more fibrous. Collagen type II expression in IGF-1 gene-transduced defects was increased 100-fold at four weeks and correlated with increased collagen type II immunoreaction up to eight months. Genetic modification of chondrocytes with AdIGF-1 prior to transplantation improved early (four to nine weeks), and to a lesser degree long-term, cartilage healing in the equine model. The equine model of cartilage healing closely resembles human clinical cartilage repair. The results of this study suggest that cartilage healing can be enhanced through genetic modification of chondrocytes prior to transplantation.
Get Full Text
Publication Date: 2007-06-02 PubMed ID: 17540757DOI: 10.1302/0301-620X.89B5.18343Google Scholar: Lookup
The Equine Research Bank provides access to a large database of publicly available scientific literature. Inclusion in the Research Bank does not imply endorsement of study methods or findings by Mad Barn.
LinkedInCopy
  • Evaluation Study
  • Journal Article
  • Research Support
  • N.I.H.
  • Extramural
  • Research Support
  • Non-U.S. Gov't

Summary

This research summary has been generated with artificial intelligence and may contain errors and omissions. Refer to the original study to confirm details provided. Submit correction.

The research is about using gene therapy to improve the healing of cartilage in horses. By altering chondrocytes (cartilage cells) with a gene coding for the Insulin-like Growth Factor-1 (IGF-1), the recovery of damaged cartilage is reportedly enhanced.

Objective and Methodology

  • The research aimed to observe whether chondrocytes genetically modified to produce Insulin-like Growth Factor-1 (IGF-1) would improve cartilage repair in horses.
  • 16 horses with single cartilage defects in their femoropatellar joint were chosen. One joint in each horse was treated with genetically modified chondrocytes while the opposite one was treated with unmodified cells for comparison.
  • The modified cells were altered using an adenovirus vector to encode for equine IGF-1. Adenovirus vectors are common tools in gene therapy, used to deliver the desired genes into cells.

Measurements and Analysis

  • The analysis took place at four weeks, nine weeks, and eight months after the surgery.
  • Aspects like the morphological and histological appearance, gene expression for IGF-1 and collagen type II, content of collagen type II and proteoglycans, and expressions for other genes related to cartilage health were evaluated.
  • The researchers used various laboratory techniques, such as Polymerase Chain Reaction (PCR), in situ hybridization, immunohistochemistry, cyanogen bromide and sodium dodecyl sulphate-polyacrylamide gel electrophoresis (SDS-PAGE), and dimethylmethylene blue assay.

Observations and Findings

  • The modified chondrocytes produced increased levels of IGF-1 mRNA and ligand for up to nine weeks, which suggests that the gene therapy was successful.
  • The genetically altered chondrocytes produced cartilage that was histologically and morphologically healthier than the control case.
  • Collagen type II expression was 100 times increased in the genetically enhanced cells at four weeks, also indicating healthier cartilage.
  • The experimental group showed significant enhancement in the cartilage healing process in four to nine weeks healing phases and a slight improvement in the long-term healing.

Implications and Conclusions

  • It is worth noting that the healing model of cartilage in horses closely matches human cartilage repair.
  • Thus, this study has implications for human health, potentially pointing to a gene therapy method that could accelerate and enhance cartilage repair.
  • The study concludes that genetically modifying chondrocytes with the IGF-1 gene before transplantation can improve cartilage healing.

Cite This Article

APA
Goodrich LR, Hidaka C, Robbins PD, Evans CH, Nixon AJ. (2007). Genetic modification of chondrocytes with insulin-like growth factor-1 enhances cartilage healing in an equine model. J Bone Joint Surg Br, 89(5), 672-685. https://doi.org/10.1302/0301-620X.89B5.18343

Publication

The Journal of bone and joint surgery. British volume
ISSN: 0301-620X
NlmUniqueID: 0375355
Country: England
Language: English
Volume: 89
Issue: 5
Pages: 672-685

Researcher Affiliations

Goodrich, L R
  • Colorado State University, College of Veterinary Medicine, Fort Collins, Colorado 80523, USA.
Hidaka, C
    Robbins, P D
      Evans, C H
        Nixon, A J

          MeSH Terms

          • Adenoviridae / genetics
          • Animals
          • Arthroscopy
          • Cartilage, Articular / injuries
          • Cartilage, Articular / metabolism
          • Cartilage, Articular / pathology
          • Cartilage, Articular / surgery
          • Chondrocytes / metabolism
          • Chondrocytes / transplantation
          • Collagen Type II / biosynthesis
          • Collagen Type II / genetics
          • Disease Models, Animal
          • Female
          • Gene Expression
          • Genetic Therapy / methods
          • Genetic Vectors
          • Horses
          • Insulin-Like Growth Factor I / biosynthesis
          • Insulin-Like Growth Factor I / genetics
          • Insulin-Like Growth Factor I / physiology
          • Male
          • Proteoglycans / metabolism
          • RNA, Messenger / genetics
          • Transduction, Genetic
          • Wound Healing

          Grant Funding

          • AR049159-02 / NIAMS NIH HHS

          Citations

          This article has been cited 57 times.
          1. Nagelli CV, Evans CH, De la Vega RE. Gene Delivery to Chondrocytes.. Adv Exp Med Biol 2023;1402:95-105.
            doi: 10.1007/978-3-031-25588-5_7pubmed: 37052849google scholar: lookup
          2. Thampi P, Samulski RJ, Grieger JC, Phillips JN, McIlwraith CW, Goodrich LR. Gene therapy approaches for equine osteoarthritis.. Front Vet Sci 2022;9:962898.
            doi: 10.3389/fvets.2022.962898pubmed: 36246316google scholar: lookup
          3. Evans CH, Ghivizzani SC, Robbins PD. Orthopaedic Gene Therapy: Twenty-Five Years On.. JBJS Rev 2021 Aug 26;9(8).
            doi: 10.2106/JBJS.RVW.20.00220pubmed: 34437305google scholar: lookup
          4. Shi S, Wang C, Trippel SB. Hyaluronic acid-binding insulin-like growth factor-1: Creation of a gene encoding a bifunctional fusion protein.. Mol Biol Rep 2020 Dec;47(12):9749-9756.
            doi: 10.1007/s11033-020-06034-wpubmed: 33263932google scholar: lookup
          5. Madry H, Venkatesan JK, Carballo-Pedrares N, Rey-Rico A, Cucchiarini M. Scaffold-Mediated Gene Delivery for Osteochondral Repair.. Pharmaceutics 2020 Sep 29;12(10).
            doi: 10.3390/pharmaceutics12100930pubmed: 33003607google scholar: lookup
          6. Weißenberger M, Weißenberger MH, Wagenbrenner M, Heinz T, Reboredo J, Holzapfel BM, Rudert M, Groll J, Evans CH, Steinert AF. Different types of cartilage neotissue fabricated from collagen hydrogels and mesenchymal stromal cells via SOX9, TGFB1 or BMP2 gene transfer.. PLoS One 2020;15(8):e0237479.
            doi: 10.1371/journal.pone.0237479pubmed: 32790806google scholar: lookup
          7. Szwedowski D, Szczepanek J, Paczesny Ł, Pękała P, Zabrzyński J, Kruczyński J. Genetics in Cartilage Lesions: Basic Science and Therapy Approaches.. Int J Mol Sci 2020 Jul 30;21(15).
            doi: 10.3390/ijms21155430pubmed: 32751537google scholar: lookup
          8. Orth P, Eldracher M, Cucchiarini M, Madry H. Small-Diameter Subchondral Drilling Improves DNA and Proteoglycan Content of the Cartilaginous Repair Tissue in a Large Animal Model of a Full-Thickness Chondral Defect.. J Clin Med 2020 Jun 18;9(6).
            doi: 10.3390/jcm9061903pubmed: 32570841google scholar: lookup
          9. Yan X, Chen YR, Song YF, Yang M, Ye J, Zhou G, Yu JK. Scaffold-Based Gene Therapeutics for Osteochondral Tissue Engineering.. Front Pharmacol 2019;10:1534.
            doi: 10.3389/fphar.2019.01534pubmed: 31992984google scholar: lookup
          10. Venkatesan JK, Rey-Rico A, Cucchiarini M. Current Trends in Viral Gene Therapy for Human Orthopaedic Regenerative Medicine.. Tissue Eng Regen Med 2019 Aug;16(4):345-355.
            doi: 10.1007/s13770-019-00179-xpubmed: 31413939google scholar: lookup
          11. Rodriguez-Merchan EC, Valentino LA. The Role of Gene Therapy in Cartilage Repair.. Arch Bone Jt Surg 2019 Mar;7(2):79-90.
            pubmed: 31211186
          12. Stewart RC, Nelson BB, Kawcak CE, Freedman JD, Snyder BD, Goodrich LR, Grinstaff MW. Contrast-Enhanced Computed Tomography Scoring System for Distinguishing Early Osteoarthritis Disease States: A Feasibility Study.. J Orthop Res 2019 Oct;37(10):2138-2148.
            doi: 10.1002/jor.24382pubmed: 31136003google scholar: lookup
          13. Barbon S, Stocco E, Macchi V, Contran M, Grandi F, Borean A, Parnigotto PP, Porzionato A, De Caro R. Platelet-Rich Fibrin Scaffolds for Cartilage and Tendon Regenerative Medicine: From Bench to Bedside.. Int J Mol Sci 2019 Apr 5;20(7).
            doi: 10.3390/ijms20071701pubmed: 30959772google scholar: lookup
          14. Shi S, Mercer S, Eckert GJ, Trippel SB. Regulation of articular chondrocyte catabolic genes by growth factor interaction.. J Cell Biochem 2019 Jul;120(7):11127-11139.
            doi: 10.1002/jcb.28389pubmed: 30809855google scholar: lookup
          15. Cucchiarini M, Madry H. Biomaterial-guided delivery of gene vectors for targeted articular cartilage repair.. Nat Rev Rheumatol 2019 Jan;15(1):18-29.
            doi: 10.1038/s41584-018-0125-2pubmed: 30514957google scholar: lookup
          16. Chen M, Guo W, Gao S, Hao C, Shen S, Zhang Z, Wang Z, Wang Z, Li X, Jing X, Zhang X, Yuan Z, Wang M, Zhang Y, Peng J, Wang A, Wang Y, Sui X, Liu S, Guo Q. Biochemical Stimulus-Based Strategies for Meniscus Tissue Engineering and Regeneration.. Biomed Res Int 2018;2018:8472309.
            doi: 10.1155/2018/8472309pubmed: 29581987google scholar: lookup
          17. Bellavia D, Veronesi F, Carina V, Costa V, Raimondi L, De Luca A, Alessandro R, Fini M, Giavaresi G. Gene therapy for chondral and osteochondral regeneration: is the future now?. Cell Mol Life Sci 2018 Feb;75(4):649-667.
            doi: 10.1007/s00018-017-2637-3pubmed: 28864934google scholar: lookup
          18. Shi S, Wang C, Chan A, Kirmani K, Eckert GJ, Trippel SB. Comparative Effectiveness of Structural versus Regulatory Protein Gene Transfer on Articular Chondrocyte Matrix Gene Expression.. Cartilage 2019 Jan;10(1):102-110.
            doi: 10.1177/1947603517719317pubmed: 28703018google scholar: lookup
          19. Aguilar IN, Trippel S, Shi S, Bonassar LJ. Customized biomaterials to augment chondrocyte gene therapy.. Acta Biomater 2017 Apr 15;53:260-267.
            doi: 10.1016/j.actbio.2017.02.008pubmed: 28185909google scholar: lookup
          20. Gugjoo MB, Sharma GT, Aithal HP, Kinjavdekar P. Cartilage tissue engineering: Role of mesenchymal stem cells along with growth factors & scaffolds.. Indian J Med Res 2016 Sep;144(3):339-347.
            doi: 10.4103/0971-5916.198724pubmed: 28139532google scholar: lookup
          21. Sacitharan PK, Vincent TL. Cellular ageing mechanisms in osteoarthritis.. Mamm Genome 2016 Aug;27(7-8):421-9.
            doi: 10.1007/s00335-016-9641-zpubmed: 27215642google scholar: lookup
          22. Goodrich LR, Chen AC, Werpy NM, Williams AA, Kisiday JD, Su AW, Cory E, Morley PS, McIlwraith CW, Sah RL, Chu CR. Addition of Mesenchymal Stem Cells to Autologous Platelet-Enhanced Fibrin Scaffolds in Chondral Defects: Does It Enhance Repair?. J Bone Joint Surg Am 2016 Jan 6;98(1):23-34.
            doi: 10.2106/JBJS.O.00407pubmed: 26738900google scholar: lookup
          23. Schwarz ML, Schneider-Wald B, Brade J, Schleich D, Schütte A, Reisig G. Instruments for reproducible setting of defects in cartilage and harvesting of osteochondral plugs for standardisation of preclinical tests for articular cartilage regeneration.. J Orthop Surg Res 2015 Jul 28;10:117.
            doi: 10.1186/s13018-015-0257-xpubmed: 26215154google scholar: lookup
          24. McIlwraith CW, Fortier LA, Frisbie DD, Nixon AJ. Equine Models of Articular Cartilage Repair.. Cartilage 2011 Oct;2(4):317-26.
            doi: 10.1177/1947603511406531pubmed: 26069590google scholar: lookup
          25. Madry H, Orth P, Cucchiarini M. Gene Therapy for Cartilage Repair.. Cartilage 2011 Jul;2(3):201-25.
            doi: 10.1177/1947603510392914pubmed: 26069580google scholar: lookup
          26. Goodrich LR, Grieger JC, Phillips JN, Khan N, Gray SJ, McIlwraith CW, Samulski RJ. scAAVIL-1ra dosing trial in a large animal model and validation of long-term expression with repeat administration for osteoarthritis therapy.. Gene Ther 2015 Jul;22(7):536-45.
            doi: 10.1038/gt.2015.21pubmed: 25902762google scholar: lookup
          27. Evans CH, Huard J. Gene therapy approaches to regenerating the musculoskeletal system.. Nat Rev Rheumatol 2015 Apr;11(4):234-42.
            doi: 10.1038/nrrheum.2015.28pubmed: 25776949google scholar: lookup
          28. Shi S, Wang C, Acton AJ, Eckert GJ, Trippel SB. Role of sox9 in growth factor regulation of articular chondrocytes.. J Cell Biochem 2015 Jul;116(7):1391-400.
            doi: 10.1002/jcb.25099pubmed: 25708223google scholar: lookup
          29. Zhao R, Peng X, Li Q, Song W. Effects of phosphorylatable short peptide-conjugated chitosan-mediated IL-1Ra and igf-1 gene transfer on articular cartilage defects in rabbits.. PLoS One 2014;9(11):e112284.
            doi: 10.1371/journal.pone.0112284pubmed: 25390659google scholar: lookup
          30. Rey-Rico A, Frisch J, Venkatesan JK, Schmitt G, Madry H, Cucchiarini M. Determination of effective rAAV-mediated gene transfer conditions to support chondrogenic differentiation processes in human primary bone marrow aspirates.. Gene Ther 2015 Jan;22(1):50-7.
            doi: 10.1038/gt.2014.90pubmed: 25338919google scholar: lookup
          31. Ortved KF, Begum L, Mohammed HO, Nixon AJ. Implantation of rAAV5-IGF-I transduced autologous chondrocytes improves cartilage repair in full-thickness defects in the equine model.. Mol Ther 2015 Feb;23(2):363-73.
            doi: 10.1038/mt.2014.198pubmed: 25311491google scholar: lookup
          32. Hemphill DD, McIlwraith CW, Samulski RJ, Goodrich LR. Adeno-associated viral vectors show serotype specific transduction of equine joint tissue explants and cultured monolayers.. Sci Rep 2014 Jul 29;4:5861.
            doi: 10.1038/srep05861pubmed: 25069854google scholar: lookup
          33. Evans C. Using genes to facilitate the endogenous repair and regeneration of orthopaedic tissues.. Int Orthop 2014 Sep;38(9):1761-9.
            doi: 10.1007/s00264-014-2423-xpubmed: 25038968google scholar: lookup
          34. Mariani E, Pulsatelli L, Facchini A. Signaling pathways in cartilage repair.. Int J Mol Sci 2014 May 15;15(5):8667-98.
            doi: 10.3390/ijms15058667pubmed: 24837833google scholar: lookup
          35. Tuan RS, Chen AF, Klatt BA. Cartilage regeneration.. J Am Acad Orthop Surg 2013 May;21(5):303-11.
            doi: 10.5435/JAAOS-21-05-303pubmed: 23637149google scholar: lookup
          36. Madry H, Kaul G, Zurakowski D, Vunjak-Novakovic G, Cucchiarini M. Cartilage constructs engineered from chondrocytes overexpressing IGF-I improve the repair of osteochondral defects in a rabbit model.. Eur Cell Mater 2013 Apr 16;25:229-47.
            doi: 10.22203/ecm.v025a17pubmed: 23588785google scholar: lookup
          37. Schneider-Wald B, von Thaden AK, Schwarz ML. [Defect models for the regeneration of articular cartilage in large animals].. Orthopade 2013 Apr;42(4):242-53.
            doi: 10.1007/s00132-012-2044-2pubmed: 23575559google scholar: lookup
          38. Kropf LL, Madeira M, Vieira Neto L, Gadelha MR, de Farias ML. Functional evaluation of the joints in acromegalic patients and associated factors.. Clin Rheumatol 2013 Jul;32(7):991-8.
            doi: 10.1007/s10067-013-2219-1pubmed: 23512376google scholar: lookup
          39. Shi S, Mercer S, Eckert GJ, Trippel SB. Growth factor regulation of growth factor production by multiple gene transfer to chondrocytes.. Growth Factors 2013 Feb;31(1):32-8.
            doi: 10.3109/08977194.2012.750652pubmed: 23302100google scholar: lookup
          40. Cucchiarini M, Orth P, Madry H. Direct rAAV SOX9 administration for durable articular cartilage repair with delayed terminal differentiation and hypertrophy in vivo.. J Mol Med (Berl) 2013 May;91(5):625-36.
            doi: 10.1007/s00109-012-0978-9pubmed: 23149825google scholar: lookup
          41. Shi S, Mercer S, Eckert GJ, Trippel SB. Growth factor transgenes interactively regulate articular chondrocytes.. J Cell Biochem 2013 Apr;114(4):908-19.
            doi: 10.1002/jcb.24430pubmed: 23097312google scholar: lookup
          42. Ng VY, Jump SS, Santangelo KS, Russell DS, Bertone AL. Genetic engineering of juvenile human chondrocytes improves scaffold-free mosaic neocartilage grafts.. Clin Orthop Relat Res 2013 Jan;471(1):26-38.
            doi: 10.1007/s11999-012-2615-xpubmed: 23008026google scholar: lookup
          43. van Eekeren IC, Reilingh ML, van Dijk CN. Rehabilitation and return-to-sports activity after debridement and bone marrow stimulation of osteochondral talar defects.. Sports Med 2012 Oct 1;42(10):857-70.
            doi: 10.1007/BF03262299pubmed: 22963224google scholar: lookup
          44. Venkatesan JK, Ekici M, Madry H, Schmitt G, Kohn D, Cucchiarini M. SOX9 gene transfer via safe, stable, replication-defective recombinant adeno-associated virus vectors as a novel, powerful tool to enhance the chondrogenic potential of human mesenchymal stem cells.. Stem Cell Res Ther 2012;3(3):22.
            doi: 10.1186/scrt113pubmed: 22742415google scholar: lookup
          45. Madry H, Cucchiarini M. Clinical potential and challenges of using genetically modified cells for articular cartilage repair.. Croat Med J 2011 Jun;52(3):245-61.
            doi: 10.3325/cmj.2011.52.245pubmed: 21674822google scholar: lookup
          46. Fortier LA, Barker JU, Strauss EJ, McCarrel TM, Cole BJ. The role of growth factors in cartilage repair.. Clin Orthop Relat Res 2011 Oct;469(10):2706-15.
            doi: 10.1007/s11999-011-1857-3pubmed: 21403984google scholar: lookup
          47. Orth P, Kaul G, Cucchiarini M, Zurakowski D, Menger MD, Kohn D, Madry H. Transplanted articular chondrocytes co-overexpressing IGF-I and FGF-2 stimulate cartilage repair in vivo.. Knee Surg Sports Traumatol Arthrosc 2011 Dec;19(12):2119-30.
            doi: 10.1007/s00167-011-1448-6pubmed: 21350959google scholar: lookup
          48. Myers TJ, Granero-Molto F, Longobardi L, Li T, Yan Y, Spagnoli A. Mesenchymal stem cells at the intersection of cell and gene therapy.. Expert Opin Biol Ther 2010 Dec;10(12):1663-79.
            doi: 10.1517/14712598.2010.531257pubmed: 21058931google scholar: lookup
          49. Miller RE, Grodzinsky AJ, Cummings K, Plaas AH, Cole AA, Lee RT, Patwari P. Intraarticular injection of heparin-binding insulin-like growth factor 1 sustains delivery of insulin-like growth factor 1 to cartilage through binding to chondroitin sulfate.. Arthritis Rheum 2010 Dec;62(12):3686-94.
            doi: 10.1002/art.27709pubmed: 20722014google scholar: lookup
          50. Goodrich LR, Choi VW, Carbone BA, McIlwraith CW, Samulski RJ. Ex vivo serotype-specific transduction of equine joint tissue by self-complementary adeno-associated viral vectors.. Hum Gene Ther 2009 Dec;20(12):1697-702.
            doi: 10.1089/hum.2009.030pubmed: 19642864google scholar: lookup
          51. Zhang H, Leng P, Zhang J. Enhanced meniscal repair by overexpression of hIGF-1 in a full-thickness model.. Clin Orthop Relat Res 2009 Dec;467(12):3165-74.
            doi: 10.1007/s11999-009-0921-8pubmed: 19526274google scholar: lookup
          52. Goldring MB, Marcu KB. Cartilage homeostasis in health and rheumatic diseases.. Arthritis Res Ther 2009;11(3):224.
            doi: 10.1186/ar2592pubmed: 19519926google scholar: lookup
          53. Koch TG, Berg LC, Betts DH. Current and future regenerative medicine - principles, concepts, and therapeutic use of stem cell therapy and tissue engineering in equine medicine.. Can Vet J 2009 Feb;50(2):155-65.
            pubmed: 19412395
          54. Verwilghen DR, Vanderheyden L, Franck T, Busoni V, Enzerink E, Gangl M, Lejeune JP, van Galen G, Grulke S, Serteyn D. Variations of plasmatic concentrations of Insulin-like Growth Factor-I in post-pubescent horses affected with developmental osteochondral lesions.. Vet Res Commun 2009 Oct;33(7):701-9.
            doi: 10.1007/s11259-009-9219-2pubmed: 19319655google scholar: lookup
          55. Gomez-Camarillo MA, Almonte-Becerril M, Vasquez Tort M, Tapia-Ramirez J, Kouri Flores JB. Chondrocyte proliferation in a new culture system.. Cell Prolif 2009 Apr;42(2):207-18.
            doi: 10.1111/j.1365-2184.2008.00580.xpubmed: 19236380google scholar: lookup
          56. Evans CH, Ghivizzani SC, Robbins PD. Orthopedic gene therapy in 2008.. Mol Ther 2009 Feb;17(2):231-44.
            doi: 10.1038/mt.2008.265pubmed: 19066598google scholar: lookup
          57. Gaddy DF, Robbins PD. Current status of gene therapy for rheumatoid arthritis.. Curr Rheumatol Rep 2008 Oct;10(5):398-404.
            doi: 10.1007/s11926-008-0064-zpubmed: 18817645google scholar: lookup
          Subscribe to our newsletter
          Join 99,344 horse owners like you who receive our email updates on horse health and nutrition.