Advanced search
Publication Cover
Expert Opinion on Biological Therapy Volume 16, 2016 - Issue 3
Submit an article Journal homepage
393
Views
30
CrossRef citations to date
0
Altmetric
Reviews

Gene therapy strategies to improve strength and quality of flexor tendon healing

Jin Bo TangDepartment of Hand Surgery, The Hand Surgery Research Center, Affiliated Hospital of Nantong University, Nantong, Jiangsu, ChinaCorrespondence[email protected]
,
You Lang ZhouDepartment of Hand Surgery, The Hand Surgery Research Center, Affiliated Hospital of Nantong University, Nantong, Jiangsu, China
,
Ya Fang WuDepartment of Hand Surgery, The Hand Surgery Research Center, Affiliated Hospital of Nantong University, Nantong, Jiangsu, China
,
Paul Y. LiuDepartment of Plastic Surgery, Rhode Island Hospital, The Alpert Medical School of Brown University, Providence, RI, USA
&
Xiao Tian WangDepartment of Plastic Surgery, Rhode Island Hospital, The Alpert Medical School of Brown University, Providence, RI, USA
Pages 291-301 | Received 06 Aug 2015, Accepted 17 Dec 2015, Published online: 06 Feb 2016

References

  • Papers of special note have been highlighted as either of interest (•) or of considerable interest (••) to readers.
  • Savage R. The search for the ideal tendon repair in zone 2: strand number, anchor points and suture thickness. J Hand Surg Eur Vol. 2014;39(1):20–29. doi:10.1177/1753193413508699. [PubMed: 24162453]
  • Wu YF, Tang JB. Recent developments in flexor tendon repair techniques and factors influencing strength of the tendon repair. J Hand Surg Eur Vol. 2014;39(1):6–19. doi:10.1177/1753193413492914. [PubMed: 23792441]
  • Tang JB, Chang J, Elliot D, et al. IFSSH Flexor Tendon Committee Report 2014: from the IFSSH Flexor Tendon Committee (Chairman: Jin Bo Tang). J Hand Surg Eur Vol. 2014;39(1):107–115. DOI:10.1177/1753193413500768. [PubMed: 23962872]
  • Tang JB, Cao Y, Zhu B, et al. Adeno-associated virus-2-mediated bFGF gene transfer to digital flexor tendons significantly increases healing strength. An in vivo study. J Bone Joint Surg Am. 2008;90(5):1078–1089. DOI:10.2106/JBJS.F.01188. [PubMed: 18451401]

•• This is a report of adeno-associated viral type 2-bFGF in enhancing tendon healing strength. The important findings include increases in the healing strength from week 2 and 8, and this therapy method did not increase tendon adhesions.

  • Tang JB. Clinical outcomes associated with flexor tendon repair. Hand Clin. 2005;21(2):199–210. doi:10.1016/j.hcl.2004.11.005. [PubMed: 15882599]
  • Branford OA, Klass BR, Grobbelaar AO, et al. The growth factors involved in flexor tendon repair and adhesion formation. J Hand Surg Eur Vol. 2014;39(1):60–70. doi:10.1177/1753193413509231. [PubMed: 24162452]
  • Moriya K, Yoshizu T, Maki Y, et al. Clinical outcomes of early active mobilization following flexor tendon repair using the six-strand technique: short- and long-term evaluations. J Hand Surg Eur Vol. 2015;40(3):250–258. DOI:10.1177/1753193414551682. [PubMed: 25249185]
  • Branski LK, Pereira CT, Herndon DN, et al. Gene therapy in wound healing: present status and future directions. Gene Ther. 2007;14(1):1–10. DOI:10.1038/sj.gt.3302837. [PubMed: 16929353]
  • Thomopoulos S, Das R, Silva MJ, et al. Enhanced flexor tendon healing through controlled delivery of PDGF-BB. J Orthop Res. 2009;27(9):1209–1215. DOI:10.1002/jor.20875. [PubMed: 19322789]

• One of the earliest report of using controlled release method to deliver growth factors to the healing tendons. Delivery of growth factor up to 6 or 7 weeks was shown to be possible in this study.

  • Yin Z, Chen X, Chen J-L, et al. Stem cells for tendon tissue engineering and regeneration. Expert Opin Biol Ther. 2010;10(5):689–700. DOI:10.1517/14712591003769824. [PubMed: 20367125]
  • Chen CH, Zhou YL, Wu YF, et al. Effectiveness of microRNA in down-regulation of TGF-beta gene expression in digital flexor tendons of chickens: in vitro and in vivo study. J Hand Surg Am. 2009;34(10):1777–84 e1. DOI:10.1016/j.jhsa.2009.07.015. [PubMed: 19969188]
  • Wang XT, Liu PY, Xin K-Q, et al. Tendon healing in vitro: bFGF gene transfer to tenocytes by adeno-associated viral vectors promotes expression of collagen genes. J Hand Surg Am. 2005;30(6):1255–1261. DOI:10.1016/j.jhsa.2005.06.001. [PubMed: 16344185]
  • Shen W, Xiao C, Chen J, et al. The effect of incorporation of exogenous stromal cell-derived factor-1 alpha within a knitted silk-collagen sponge scaffold on tendon regeneration. Biomaterials. 2010;31(28):7239–7249. DOI:10.1016/j.biomaterials.2010.01.042. [PubMed: 20615544]
  • Reed SA, Leahy ER. Growth and Development Symposium: stem cell therapy in equine tendon injury. J Anim Sci. 2013;91(1):59–65. DOI:10.2527/jas.2012-5736. [PubMed: 23100589]
  • Harvey DM, Caskey CT. Inducible control of gene expression: prospects for gene therapy. Curr Opin Chem Biol. 1998;2(4):512–518. [PubMed: 9736925]
  • Evans CH, Huard J Gene therapy approaches to regenerating the musculoskeletal system. Nat Rev Rheumatol. 2015;11(4): 234–242. DOI:10.1038/nrrheum.2015.28. [PubMed: 25776949]

• This review highlights what are unique in gene therapy for musculoskeletal system. The requirement in this system is very different from treatment of genetic diseases or tumors which have been discussed intensively thus far.

  • Zhu B, Cao Y, Xin K-Q, et al. Tissue reactions of adenoviral, adeno-associated viral, and liposome-plasmid vectors in tendons and comparison with early-stage healing responses of injured flexor tendons. J Hand Surg Am. 2006;31(10):1652–1660. DOI:10.1016/j.jhsa.2006.09.007. [PubMed: 17145387]
  • Wang XT, Liu PY, Tang JB, et al. Tendon healing in vitro: adeno-associated virus-2 effectively transduces intrasynovial tenocytes with persistent expression of the transgene, but other serotypes do not. Plast Reconstr Surg. 2007;119(1):227–234. DOI:10.1097/01.prs.0000244861.57040.3f. [PubMed: 17255678]
  • Bolt P, Clerk AN, Luu HH, et al. BMP-14 gene therapy increases tendon tensile strength in a rat model of Achilles tendon injury. J Bone Joint Surg Am. 2007;89(6):1315–1320. DOI:10.2106/JBJS.F.00257. [PubMed: 17545436]
  • Uggen JC, Dines J, Uggen CW, et al. Tendon gene therapy modulates the local repair environment in the shoulder. J Am Osteopath Assoc. 2005;105(1):20–21. [PubMed: 15710662]
  • Chen CH, Cao Y, Wu YF, et al. Tendon healing in vivo: gene expression and production of multiple growth factors in early tendon healing period. J Hand Surg Am. 2008;33(10):1834–1842. DOI:10.1016/j.jhsa.2008.07.003. [PubMed: 19084187]
  • Rickert M, Wang H, Wieloch P, et al. Adenovirus-mediated gene transfer of growth and differentiation factor-5 into tenocytes and the healing rat Achilles tendon. Connect Tissue Res. 2005;46(4–5):175–183. DOI:10.1080/03008200500237120. [PubMed: 16546820]
  • Jueren L, Yizheng T, Meghan B, et al. BMP-12 gene transfer augmentation of lacerated tendon repair. J Orthop Res. 2001;19(6):1199–202(4). DOI:10.1016/S0736-0266(01)00042-0. [PubMed: 11781024]
  • Park HJ, Lee J, Kim MJ, et al. Sonic hedgehog intradermal gene therapy using a biodegradable poly(beta-amino esters) nanoparticle to enhance wound healing. Biomaterials. 2012;33(35):9148–9156. DOI:10.1016/j.biomaterials.2012.09.005. [PubMed: 23018131]
  • Figueroa ER, Lin AY, Yan J, et al. Optimization of PAMAM-gold nanoparticle conjugation for gene therapy. Biomaterials. 2014;35(5):1725–1734. DOI:10.1016/j.biomaterials.2013.11.026. [PubMed: 24286816]
  • Xu W, Wang Y, Li S, et al. Efficient gene and siRNA delivery with cationic polyphosphoramide with amino moieties in the main chain. RSC Advances. 2015;125(1):25–32. [PubMed: 17976853]
  • Lo YL, Lo PC, Chiu CC, et al. Folic acid linked chondroitin sulfate-polyethyleneimine copolymer based gene delivery system. J Biomed Nanotechnol. 2015;11:1385–1400(1316). [PubMed: 26295140]
  • Yin H, Kanasty RL, Eltoukhy AA, et al. Non-viral vectors for gene-based therapy. Nat Rev Genet. 2014;15(8):541–555. DOI:10.1038/nrg3763. [PubMed: 25022906]
  • Jin S, Ye K. Nanoparticle-mediated drug delivery and gene therapy. Biotechnol Prog. 2007;23(1):32–41. doi:10.1021/bp060348j. [PubMed: 17269667]
  • Ramamoorth M, Narvekar A. Non viral vectors in gene therapy - an overview. J Clin Diagn Res. 2015;9(1):GE01–6. DOI:10.7860/JCDR/2015/10443.5394. [PubMed: 25738007]
  • Suwalski A, Dabboue H, Delalande A, et al. Accelerated Achilles tendon healing by PDGF gene delivery with mesoporous silica nanoparticles. Biomaterials. 2010;31(19):5237–5245. DOI:10.1016/j.biomaterials.2010.02.077. [PubMed: 20334910]
  • Brevet D, Hocine O, Delalande A, et al. Improved gene transfer with histidine-functionalized mesoporous silica nanoparticles. Int J Pharm. 2014;471(1–2):197–205. DOI:10.1016/j.ijpharm.2014.05.020. [PubMed: 24853464]
  • Zhou YL, Zhang LZ, Zhao WX, et al. Nanoparticle-mediated delivery of TGF-β1 miRNA plasmid for preventing flexor tendon adhesion formation. Biomaterials. 2013;34(33):8269–8278. DOI:10.1016/j.biomaterials.2013.07.072. [PubMed: 23924908]
  • Zhou YL, Zhu CL, Wu YF, et al. Effective modulation of transforming growth factor-β1 expression through engineered microRNA-based plasmid-loaded nanospheres. Cytotherapy. 2014;17(3):320–329. DOI:10.1016/j.jcyt.2014.09.004. [PubMed: 25457276]

• A report showing possibility and efficiency of delivery of micro-RNA through poly(D, L-lactide-co-glycolide)-nanoparticle system in a controlled release system.

  • Panyam J, Zhou WZ, Prabha S, et al. Rapid endo-lysosomal escape of poly(DL-lactide-co-glycolide) nanoparticles: implications for drug and gene delivery. FASEB J. 2002;16(10):1217–1226. DOI:10.1096/fj.02-0088com. [PubMed: 12153989]
  • Yalamanchi N, Klein MB, Pham HM, et al. Flexor tendon wound healing in vitro: lactate up-regulation of TGF-beta expression and functional activity. Plast Reconstr Surg. 2004;113(2):625–632. DOI:10.1097/01.PRS.0000101529.47062.34. [PubMed: 14758225]
  • Kashiwagi K, Mochizuki Y, Yasunaga Y, et al. Effects of transforming growth factor-beta 1 on the early stages of healing of the Achilles tendon in a rat model. Scand J Plast Reconstr Surg Hand Surg. 2004;38(4):193–197. DOI:10.1080/02844310410029110. [PubMed: 15370799]
  • Yang G, Crawford RC, Wang JH. Proliferation and collagen production of human patellar tendon fibroblasts in response to cyclic uniaxial stretching in serum-free conditions. J Biomech. 2004;37(10):1543–1550. DOI:10.1016/j.jbiomech.2004.01.005. [PubMed: 15336929]
  • Sporn MB, Roberts AB. Transforming growth factor-beta: recent progress and new challenges. J Cell Biol. 1992;119(5):1017–1021. [PubMed: 1332976]
  • Chan KM, Fu SC, Wong YP, et al. Expression of transforming growth factor β isoforms and their roles in tendon healing. Wound Repair Regen. 2008;16(3):399–407. DOI:10.1111/j.1524-475X.2008.00379.x. [PubMed: 18471258]
  • Bates SJ, Morrow E, Zhang AY, et al. Mannose-6-phosphate, an inhibitor of transforming growth factor-beta, improves range of motion after flexor tendon repair. J Bone Joint Surg Am. 2006;88(11):2465–2472. DOI:10.2106/JBJS.E.00143. [PubMed: 17079405]
  • Jorgensen HG, McLellan SD, Crossan JF, et al. Neutralisation of TGF beta or binding of VLA-4 to fibronectin prevents rat tendon adhesion following transection. Cytokine. 2005;30(4):195–202. DOI:10.1016/j.cyto.2004.12.017. [PubMed: 15863394]
  • Chen CH, Zhou YL, Wu YF, et al. Effectiveness of microRNA in down-regulation of TGF-β gene expression in digital flexor tendons of chickens: in vitro and in vivo study. J Hand Surg Am. 2009;34(10):1777–1784. DOI:10.1016/j.jhsa.2009.07.015. [PubMed: 19969188]
  • Loiselle AE, Yukata K, Geary MB, et al. Development of antisense oligonucleotide (ASO) technology against TGF-β signaling to prevent scarring during flexor tendon repair. J Orthop Res. 2015;33(6):859–866. DOI:10.1002/jor.22890. [PubMed: 25761254]
  • Tang Y, Leng Q, Xiang X, et al. Use of ultrasound-targeted microbubble destruction to transfect IGF-1 cDNA to enhance the regeneration of rat wounded Achilles tendon in vivo. Gene Ther. 2015. 22 610–618 DOI:10.1038/gt.2015.32. [PubMed: 25840275]
  • Massague J, Blain SW, Lo RS. TGF-beta signaling in growth control, cancer, and heritable disorders. Cell. 2000;103(2):295–309. [PubMed: 11057902]
  • Derynck R, Akhurst RJ. Differentiation plasticity regulated by TGF-beta family proteins in development and disease. Nat Cell Biol. 2007;9(9):1000–1004. DOI:10.1038/ncb434. [PubMed: 17762890]
  • Letterio JJ, Roberts AB. Regulation of immune responses by TGF-beta. Annu Rev Immunol. 1998;16:137–161. DOI:10.1146/annurev.immunol.16.1.137. [PubMed: 9597127]
  • Assoian RK, Komoriya A, Meyers CA, et al. Transforming growth factor-beta in human platelets. Identification of a major storage site, purification, and characterization. J Biol Chem. 1983;258(11):7155–7160. [PubMed: 6602130]
  • Lebman DA, Edmiston JS. The role of TGF-beta in growth, differentiation, and maturation of B lymphocytes. Microbes Infect. 1999;1(15):1297–1304. [PubMed: 10611758]
  • Massague J. TGFbeta in Cancer. Cell. 2008;134(2):215–230. DOI:10.1016/j.cell.2008.07.001. [PubMed: 18662538]
  • Pines M. Targeting TGFβ signaling to inhibit fibroblast activation as a therapy for fibrosis and cancer: effect of halofuginone. Expert Opin Drug Discov. 2008;3(1):11–20. DOI:10.1517/17460441.3.1.11. [PubMed: 23480137]
  • Zhang YE. Non-Smad pathways in TGF-beta signaling. Cell Res. 2009;19(1):128–139. DOI:10.1038/cr.2008.328. [PubMed: 19114990]
  • Okuda K, Murata M, Sugimoto M, et al. TGF-beta1 influences early gingival wound healing in rats: an immunohistochemical evaluation of stromal remodelling by extracellular matrix molecules and PCNA. J Oral Pathol Med. 1998;27(10):463–469. [PubMed: 9831957]
  • Poppas DP, Massicotte JM, Stewart RB, et al. Human albumin solder supplemented with TGF‐β1 accelerates healing following laser welded wound closure. Lasers Surg Med. 1996;19(3):360–368. DOI:10.1002/(SICI)1096-9101(1996)19:3<360::AID-LSM13>3.0.CO;2-8. [PubMed: 8923433]
  • Chesnoy S, Lee P-Y, Huang L. Intradermal injection of transforming growth factor-beta1 gene enhances wound healing in genetically diabetic mice. Pharm Res. 2003;20(3):345–350. [PubMed: 12669952]
  • Lee PY, Li Z, Huang L. Thermosensitive hydrogel as a TGF-β1 gene delivery vehicle enhances diabetic wound healing. Pharm Res. 2003;20(12):1995–2000. [PubMed: 14725365]
  • Viger ML, Grossman M, Fomina N, et al. Low power upconverted near-IR light for efficient polymeric nanoparticle degradation and cargo release. Adv Mater. 2013;25(27):3733–3738. DOI:10.1002/adma.201300902. [PubMed: 23722298]

Reprints and Corporate Permissions

Please note: Selecting permissions does not provide access to the full text of the article, please see our help page How do I view content?

To request a reprint or corporate permissions for this article, please click on the relevant link below:

Order Reprints Request Corporate Permissions

Academic Permissions

Please note: Selecting permissions does not provide access to the full text of the article, please see our help page How do I view content?

Obtain permissions instantly via Rightslink by clicking on the button below:

Request Academic Permissions

If you are unable to obtain permissions via Rightslink, please complete and submit this Permissions form. For more information, please visit our Permissions help page.

Related research

People also read lists articles that other readers of this article have read.

Recommended articles lists articles that we recommend and is powered by our AI driven recommendation engine.

Cited by lists all citing articles based on Crossref citations.
Articles with the Crossref icon will open in a new tab.