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Review article: Biomedical intelligence

Vol. 144 No. 3132 (2014)

Cell therapies for tendons: Old cell choice for modern innovation

  • Lee Laurent-Applegate
  • Anthony Grognuz
  • Nathalie Hirt-Burri
  • Ilias Petrou
  • Wassim Raffoul
DOI
https://doi.org/10.4414/smw.2014.13989
Cite this as:
Swiss Med Wkly. 2014;144:w13989
Published
27.07.2014

Abstract

Although tissue engineering and cell therapies are becoming realistic approaches for medical therapeutics, it is likely that musculoskeletal applications will be among the first to benefit on a large scale. Cell sources for tissue engineering and cell therapies for tendon pathologies are reviewed with an emphasis on small defect tendon injuries as seen in the hand which could adapt well to injectable cell administration. Specifically, cell sources including tenocytes, tendon sheath fibroblasts, bone marrow or adipose-derived stem cells, amniotic cells, placenta cells and platelet-derivatives have been proposed to enhance tendon regeneration. The associated advantages and disadvantages for these different strategies will be discussed and evolving regulatory requirements for cellular therapies will also be addressed. Human progenitor tenocytes, along with their clinical cell banking potential, will be presented as an alternative cell source solution. Similar cell banking techniques have already been described with other progenitor cell types in the 1950’s for vaccine production, and these “old” cell types incite potentially interesting therapeutic options that could be improved with modern innovation for tendon regeneration and repair.

References

  1. Service de centralization des statistiques de l’assurance accident LAA. http://www.unfallstatistik.ch
  2. Verdan CE. Half a century of flexor-tendon surgery. Current status and changing philosophies. J Bone Joint Surg Am. 1972;54(3):472–91.
  3. Sharma P, Maffulli N. Tendon injury and tendinopathy: healing and repair. J Bone Joint Surg Am. 2005;87(1):187–202.
  4. Voleti PB, Buckley MR, Soslowsky LJ. Tendon healing: repair and regeneration. Annual Rev Biomed Eng. 2012;14:47–71.
  5. Kannus P. Structure of the tendon connective tissue. Scand J Med Sci Sports. 2000;10(6):312–20.
  6. O’Brien M. Structure and metabolism of tendons. Scand J Med Sci Sports. 1997;7(2):55–61.
  7. Tai CC, Williams A. Ligaments and tendons, in Basic Orthopaedic Sciences, Ed. Ramachandram, CRC Press 2006, chapter 8, pp. 71–78.
  8. James R, Kesturu G, Balian G, Chhabra AB. Tendon: biology, biomechanics, repair, growth factors, and evolving treatment options. J Hand Surg Am. 2008;33(1):102–12
  9. Chen X, Song XH, Yin Z, Zou X-Y, Wang L-L, Hu H, et al. Stepwise differentiation of human embryonic stem cells promotes tendon regeneration by secreting fetal tendon matrix and differentiation factors. Stem Cells. 2009;27(6):1276–1287.
  10. Watts AE, Yeager AE, Kopyov OV, Nixon AJ. Fetal derived embryonic-like stem cells improve healing in a large animal flexor tendonitis model. Stem Cell Res Ther. 2011;2(1):4.
  11. Ferrara JL, Cooke KR, Teshima T. The pathophysiology of acute graft-versus-host disease. Int J Hematol. 2003;78(3):181–7.
  12. Petersdorf EW, Shuler KB, Longton GM, Spies T, Hansen JA. Population study of allelic diversity in the human MHC class I-related MIC-A gene. Immunogenetics. 1999;49(7–8):605–12.
  13. Mack GS. Osiris seals billion-dollar deal with Genzyme for cell therapy. Nature Biotech. 2009;27(2):106–7.
  14. Klar AS, Güven S, Biedermann T, Luginbühl J, Böttcher-Haberzeth S, Meuli-Simmen C, Meuli M, Martin I, Scherberich A, Reichmann E. Tissue-engineered dermo-epidermal skin grafts prevascularized with adipose-derived cells. Biomaterials. 2014;35(19):5065–78.
  15. Böttcher-Haberzeth S, Biedermann T, Klar AS, Pontiggia L, Rac J, Nadal D, et al. Tissue engineering of skin: human tonsil-derived mesenchymal cells can function as dermal fibroblasts. Pediatr Surg Int. 2014;30(2):213–22.
  16. Daniela Marino, Joachim Luginbühl, Simonetta Scola, Martin Meuli, Ernst Reichmann. Bioengineering Dermo-Epidermal Skin Grafts with Blood and Lymphatic Capillaries. Sci Transl Med. 2014;6(221): 221ra14 DOI: 10.1126/scitranslmed.3006894.
  17. Pontiggia L, Klar AS, Böttcher-Haberzeth S, Biedermann T, Meuli M, Reichmann E. Optimizing in vitro culture conditions leads to a significantly shorter production time of human dermo-epidermal skin substitutes. Pediatr Surg Int. 2013;29(3):249–56.
  18. Ju YJ, Muneta T, Yoshimura H, Koga H, Sekiya I. Synovial mesenchymal stem cells accelerate early remodeling of tendon-bone healing. Cell Tissue Res. 2008;332(3):469–78.
  19. Lacitignola L, Crovace A, Rossi G, Francioso E. Cell therapy for tendinitis, experimental and clinical report. Vet Res Commun. 2008;32:s33–38.
  20. Nixon AJ, Dahlgren LA, Haupt JL, Yeager AE, Ward DL. Effect of adipose-derived nucleated cell fractions on tendon repair in horses with collagenase-induced tendinitis. Am J Vet Res. 2008;69(7):928–37.
  21. Smith RK. Mesenchymal stem cell therapy for equine tendinopathy. Disabil Rehabil. 2008;30(20–22 ):1752–8.
  22. Favata M, Beredjiklian PK, Zgonis MH, Beason DP, Crombleholme TM, Jawad AF, Soslowsky LJ. Regenerative properties of fetal sheep tendon are not adversely affected by transplantation into an adult environment. J Orthop Res. 2006;24(11):2124–32.
  23. Beredjiklian PK, Favata M, Cartmell JS, Flanagan CL, Crombleholme TM, Soslowsky LJ. Regenerative versus reparative healing in tendon: a study of biomechanical and histological properties in fetal sheep. Annals of Biom Eng. 2003;31(10):1143–52.
  24. Kryger GS, Chong AKS, Costa M, Pham H, Bates SJ, Chang J. A comparison of tenocytes and mesenchymal stem cells for use in flexor tendon tissue engineering. J Hand Surg. 2007;32(5):597–605.
  25. Ouyang HW,Goh JCH, Thambyah A, Teoh SH, Lee EH. Knitted poly-lactide-co-glycolide scaffold loaded with bone marrow stromal cells in repair and regeneration of rabbit achilles tendon. Tissue Eng. 2003;9(3):431–9.
  26. Chong AKS, Ang AD, Goh JCH, Hui JHP, Lim AYT, Lee EH, et al. Bone marrow derived mesenchymal stem cells influence early tendon-healing in a rabbit Achilles tendon model. J Bone Joint Surgery A. 2007;89(1):74–81.
  27. Gulotta LV, Kovacevic D, Packer JD, Deng XH, Rodeo SA. Bone marrow-derived mesenchymal stem cells transduced with scleraxis improve rotator cuff healing in a rat model. Am J Sports Med. 2011;39(6):1282–9.
  28. Ellera Gomes JL, Canquerini da Silva R, Silla LMR, Abreu MR, Pellanda R. Conventional rotator cuff repair complemented by the aid of mononuclear autologous stem cells. Knee Surg Sports Traumatol Arthrosc. 2012;20(2):373–7.
  29. Bi Y, Ehirchiou D, Kilts TM, Inkson CA, Embree MC, Sonoyama W, et al. Identification of tendon stem/progenitor cells and the role of the extracellular matrix in their niche. Nature Med. 2007;13(10):1219–27.
  30. Fernández-Sarmiento JA, Domínguez JM, Granados MM, Morgaz J, Navarrete R, Carrillo JM, et al. Histological study of the influence of plasma rich in growth factors (PRGF) on the healing of divided Achilles tendons in sheep. J Bone Joint Surg Am. 2013;95(3):246–55.
  31. Sato D, Takahara M, Narita A, Yamakawa J, Hashimoto J, Ishikawa H, Ogino T. Effect of platelet-rich plasma with fibrin matrix on healing of intrasynovial flexor tendons. J Hand Surg Am. 2012;37(7):1356–63.
  32. Cid J, Harm SK, Yazer MH. Platelet transfusion – the art and science of compromise. Transfus Med Hemother. 2013;40(3):160–71.
  33. Schepull T, Kvist J, Norrman H, Trinks M, Berlin G, Aspenberg P. Autologous platelets have no effect on the healing of human achilles tendon ruptures: a randomized single-blind study. Am J Sports Med. 2011;39(1):38–47.
  34. Akhundov K, Pietramaggiori G, Waselle L, Darwiche S, Guerid S, Scaletta C, et al. Development of a Cost-Effective Method for Platelet Rich Plasma (PRP) Preparation for Topical Wound Healing. Ann Burns Fire Disasters. 2012;25(4):207–13.
  35. Kaviani A, Guleserian K, Perry TE, Russel W, Jennings RW, Moritz M, et al. Fetal tissue engineering from amniotic fluid. J Am Coll Surg. 2003;196(4):592–7.
  36. Kadner A, Hoerstrup SP, Tracy J, Breymann C, Maurus CF, Melnitchouk S, et al. Human umbilical cord cells: A new cell source for cardiovascular tissue engineering. Ann Thorac Surg. 2002;74:S1422–8.
  37. Kaviani A, Perry TE, Barnes CM, Oh JT, Ziegler MM, Fishman SJ, et al. The placenta as a cell source in fetal tissue engineering. J Pediatr Surg. 2002;37:995–9.
  38. Applegate LA, Weber D, Simon J-P, Scaletta C, Hirt-Burri N, de Buys Roessingh A, Raffoul W. Chapter 7 – Organ donation and whole-cell bioprocessing in the Swiss Fetal Progenitor Cell Transplantation Platform. Ed. RF Saidi, Organ Donation and Organ Donors. Nova Science Publishers; 2013. p.125–147.
  39. Rosser AE, Bachoud-Lévi A-C. Clinical trials of neural transplantation in Huntington’s disease. Prog Brain Res. 2012;200:345–71.
  40. Schackel S, Pauly M-C, Piroth T, Nikkhah G, Döbrössy MD. Donor age dependent graft development and recovery in a rat model of Huntington’s disease: Histological and behavioral analysis. Behav Brain Res. 2013;256:56–63.
  41. Lindvall, O. Developing dopaminergic cell therapy for Parkinson’s disease – give up or move forward? Mov. Disord. 2013;28(3):268–73.
  42. Wirth ED 3rd, Reier PJ, Fessler RG, Thompson FJ, Uthman B, Behrman A, et al. Feasibility and safety of neural tissue transplantation in patients with syringomyelia. J Neurotrauma. 2001;18(9):911–29.
  43. Akesson E, Piao JH, Samuelsson EB, Holmberg L, Kjaeldgaard A, Falci S, et al. Long-term culture and neuronal survival after intraspinal transplantation of human spinal cord-derived neurospheres. Physiol Behav. 2007;92(1–2):60–6.
  44. Iwai H, Nori S, Nishimura S, Yasuda A, Takano M, Tsuji O, et al. Transplantation of neural stem/progenitor cells at different locations in mice with spinal cord injury. Cell Transplant. 2013 Aug 30. doi: 10.3727/096368913X670967. (Epub ahead of print)
  45. Mothe, AJ, Tator CH. Review of transplantation of neural stem/progenitor cells for spinal cord injury. Int J Dev Neurosci. 2013;31(7):701–13.
  46. Touraine JL, Raudrant D, Golfier F, Rebaud A, Sembeil R, Roncarolo MG, et al. Reappraisal of in utero stem cell transplantation based on long-term results. Fetal Diagn Ther. 2004;19(4):305–12.
  47. Montanucci P, Pennoni I, Pescara T, Basta G, Calafiore R. Treatment of diabetes mellitus with microencapsulated fetal human liver (FH-B-TPN) engineered cells. Biomaterials. 2013;34(16):4002–12.
  48. Zaret KS, Grompe M. Generation and regeneration of cells of the liver and pancreas. Science. 2008;322(5907):1490–4.
  49. Gridelli B, Vizzini G, Pietrosi G, Luca A, Spada M, Gruttadauria S, et al. Efficient human fetal liver cell isolation protocol based on vascular perfusion for liver cell–based therapy and case report on cell transplantation. Liver Transpl. 2012;18(2):226–37.
  50. Khan AA, Shaik MV, Parveen N, Rajendraprasad A, Aleem MA, Habeeb MA, et al. Human fetal liver-derived stem cell transplantation as supportive modality in the management of end-stage decompensated liver cirrhosis. Cell Transplant. 2010;19(4):409–18.
  51. Hohlfeld J, de Buys Roessingh A, Hirt-Burri N, Chaubert P, Gerber S, Scaletta C, et al. Tissue engineered fetal skin constructs for paediatric burns. Lancet. 2005;366:840–2.
  52. Ramelet A-A, Hirt-Burri N, Raffoul W, Scaletta C, Pioletti D, Offord E, et al. Chronic wound healing by fetal cell therapy may be explained by differential gene profiling observed in fetal versus old skin cells. Exp Gerontol. 2009;44:208–18.
  53. Applegate LA, Weber D, Simon J-P, Scaletta C, de Buys Roessingh A, Raffoul W. Organ donation and whole-cell bioprocessing in the swiss fetal progenitor cell transplantation program. In: Organ donation and Organ donors: Issues, challenges and perspectives. Nova Science Publishers, Ed. Saidi RF. pp 125–147, 2013.
  54. Pioletti DP, Montjovent MO, Zambelli PY, Applegate L. Bone tissue engineering using foetal cell therapy. Swiss Med Wkly. 2006;136(35–36):557–60.
  55. Darwiche S, Scaletta C, Raffoul W, Pioletti DP, Applegate LA. Epiphyseal Chondroprogenitors Provide a Stable Cell Source for Cartilage Cell Therapy. Cell Medicine. 2012;4:23–32.
  56. Tenorio DM, Scaletta C, Jaccoud S, Hirt-Burri N, Pioletti DP, Jaques B, Applegate LA. Human fetal bone cells in delivery systems for bone engineering. J Tissue Eng Regen Med. 2011;5(10):806–14.

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