Skip to main content

Advertisement

Log in

Tendon-Derived Stem Cells (TDSCs): From Basic Science to Potential Roles in Tendon Pathology and Tissue Engineering Applications

  • Published:
Stem Cell Reviews and Reports Aims and scope Submit manuscript

Abstract

Traditionally, tendons are considered to only contain tenocytes that are responsible for the maintenance, repair and remodeling of tendons. Stem cells, which are termed tendon-derived stem cells (TDSCs), have recently been identified in tendons. This review aims to summarize the current information about the in vitro characteristics of TDSCs, including issues related to TDSC isolation and culture, their cell morphology, immunophenotypes, proliferation and differentiation characteristics and senescence during in vitro passaging. The challenges in studying the functions of these cells are also discussed. The niche where TDSCs resided essentially provides signals that are conducive to the maintenance of definitive stem cell properties of TDSCs. Yet the niche may also induce pathologies by imposing an aberrant function on TDSCs or other targets. The possible niche factors of TDSCs are herein discussed. We presented current evidences supporting the potential pathogenic role of TDSCs in the development of tendinopathy with reference to the recent findings on the altered biological responses of these cells in response to their potential niche factors. The use of resident stem cells may promote engraftment and differentiation of transplanted cells in tendon and tendon–bone junction repair because the tendon milieu is an ideal and familiar environment to the transplanted cells. Evidences are presented to show the potential advantages and results of using TDSCs as a new cell source for tendon and tendon–bone junction repair. Issues pertaining to the use of TDSCs for tissue repair are also discussed.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Fig. 1
Fig. 2

Similar content being viewed by others

References

  1. Salingcarnboriboon, R., Yoshitake, H., Tsuji, K., et al. (2003). Establishment of tendon-derived cell lines exhibiting pluripotent mesenchymal stem-like property. Experimental Cell Research, 287, 289–300.

    Article  PubMed  CAS  Google Scholar 

  2. Scutt, N., Rolf, C. G., & Scutt, A. (2006). Glucocorticoids inhibit tenocyte proliferation and tendon progenitor cell recruitment. Journal of Orthopaedic Research, 24(2), 173–182.

    Article  PubMed  CAS  Google Scholar 

  3. Strassburg, S., Smith, R., Goodship, A., Hardingham, T., & Clegg, P. (2006). Adult and late fetal equine tendons contain cell populations with weak progenitor properties in comparison to bone marrow derived mesenchymal stem cells. Transection of Orthopaedic Research Society Annual Meeting, 31, 1113.

    Google Scholar 

  4. de Mos, M., Koevoet, W. J., Jahr, H., et al. (2007). Intrinsic differentiation potential of adolescent human tendon tissue: an in-vitro cell differentiation study. BMC Musculoskeletal Disorder, 8, 16.

    Article  Google Scholar 

  5. Hashimoto, Y., Yoshida, G., Toyoda, H., & Takaoka, K. (2007). Generation of tendon-to-bone interface ‘enthesis’ with the use of recombinant BMP-2 in a rabbit model. Journal of Orthopaedic Research, 25, 1415–1424.

    Article  PubMed  Google Scholar 

  6. Bi, Y., Ehirchiou, D., Kilts, T. M., et al. (2007). Identification of tendon stem / progenitor cells and the role of the extracellular matrix in their niche. Nature Medicine, 13(10), 1219–1227.

    Article  PubMed  CAS  Google Scholar 

  7. Zhang, J., & Wang, J. H. C. (2010). Characterization of differential properties of rabbit tendon stem cells and tenocytes. BMC Musculoskeletal Disorder, 11, 10.

    Article  CAS  Google Scholar 

  8. Rui, Y. F., Lui, P. P. Y., Li, G., Fu, S. C., Lee, Y. W., & Chan, K. M. (2010). Isolation and characterization of multi-potent rat tendon-derived stem cells. Tissue Engineering Part A, 16(5), 1549–1558.

    Article  PubMed  CAS  Google Scholar 

  9. Yin, Z., Chen, X., Chen, J. L., et al. (2010). The regulation of tendon stem cell differentiation by the alignment of nanofibers. Biomaterials, 31(8), 2163–2175.

    Article  PubMed  CAS  Google Scholar 

  10. Zhang, J., Pan, T., Liu, Y., & Wang, J. H. (2010). Mouse treadmill running enhances tendons by expanding the pool of tendon stem cells (TSCs) and TSC-related cellular production of collagen. Journal of Orthopaedic Research, 28(9), 1178–1183.

    Article  PubMed  Google Scholar 

  11. Zhang, J., & Wang, J. H. (2010). Platelet-rich plasma releasate promotes differentiation of tendon stem cells into active tenocytes. American Journal of Sports Medicine, 38(12), 2477–2486.

    Article  PubMed  Google Scholar 

  12. Colter, D. C., Clas, R., DiGirolamo, C. M., & Prockop, D. J. (2000). Rapid expansion of recycling stem cells in cultures of plastic-adherent cells from human bone marrow. Proceedings of the National Academy of Sciences of the United States of America, 97(7), 3213–3218.

    Article  PubMed  CAS  Google Scholar 

  13. Dezawa, M., Ishikawa, H., Itokazu, Y., et al. (2005). Bone marrow stromal cells generate muscle cells and repair muscle degeneration. Science, 309(5732), 314–317.

    Article  PubMed  CAS  Google Scholar 

  14. Rui, Y. F., Lui, P. P. Y., Ni, M., Chan, L. S., Lee, Y. W., & Chan, K. M. (2011). Mechanical loading increased BMP-2 expression which promoted osteogenic differentiation of tendon-derived stem cells. Journal of Orthopaedic Research, 29(3), 390–396.

    Article  PubMed  CAS  Google Scholar 

  15. Rui, Y. F., Lui, P. P. Y., Ni, M., et al. (2010). Higher expression of BMP receptors and BMP-2-induced osteogenesis in tendon-derived stem cells compared to bone marrow-derived stem cells. 7th Combined Meeting of the Orthopaedic Research Societies. 16th–20th Oct, 2010, Kyoto International Conference Centre, Kyoto, Japan.

  16. Zhou, Z., Akinbiyi, T., Xu, L., et al. (2010). Tendon-derived stem / progenitor cell aging: defective self-renewal and altered fate. Aging Cell, 9(5), 911–915.

    Article  PubMed  CAS  Google Scholar 

  17. Stenderup, K., Justesen, J., Eriksen, E. F., Rattan, S. I., & Kassem, M. (2001). Number and proliferative capacity of osteogenic stem cells are maintained during aging and in patients with osteoporosis. Journal of Bone and Mineral Research, 16, 1120–1129.

    Article  PubMed  CAS  Google Scholar 

  18. Pittenger, M. F., Mackay, A. M., Beck, S. C., et al. (1999). Multilineage potential of adult human mesenchymal stem cells. Science, 284, 143–047.

    Article  PubMed  CAS  Google Scholar 

  19. Halfon, S., Abramov, N., Grinblat, B., & Ginis, I. (2011). Markers distinguishing mesenchymal stem cells from fibroblasts are downregulated with passaging. Stem Cells and Development, 20(1), 53–66.

    Article  PubMed  CAS  Google Scholar 

  20. Rombouts, W. J., & Ploemacher, R. E. (2003). Primary murine MSC show highly efficient homing to the bone marrow but lose homing ability following culture. Leukemia, 17(1), 160–170.

    Article  PubMed  CAS  Google Scholar 

  21. Azizi, S. A., Stokes, D., Augelli, B. J., DiGirolamo, C., & Prockop, D. J. (1998). Engraftment and migration of human bone marrow stromal cells implanted in the brains of albino rats—similarities to astrocyte grafts. Proceedings of the National Academy of Sciences of the United States of America, 95, 3908–3913.

    Article  PubMed  CAS  Google Scholar 

  22. Kopen, G. C., Prockop, D. J., & Phinney, D. G. (1999). Marrow stromal cells migrate throughout forebrain and cerebellum, and they differentiate into astrocytes after injection into neonatal mouse brains. Proceedings of the National Academy of Sciences of the United States of America, 96, 10711–10716.

    Article  PubMed  CAS  Google Scholar 

  23. Fukuda, K. (2002). Molecular characterization of regenerated cardiomyocytes derived from adult mesenchymal stem cells. Congenital Anomalies (Kyoto), 42, 1–9.

    Article  CAS  Google Scholar 

  24. Makino, S., Fukuda, K., Miyoshi, S., et al. (1999). Cardiomyocytes can be generated from marrow stromal cells in vitro. Journal of Clinical Investigation, 103, 697–705.

    Article  PubMed  CAS  Google Scholar 

  25. Kuo, T. K., Ho, J. H., & Lee, O. K. (2009). Mesenchymal stem cell therapy for nonmusculoskeletal diseases: emerging applications. Cell Transplantation, 18, 1013–1028.

    Article  PubMed  Google Scholar 

  26. Wang, J. S., Shum-Tim, D., Galipeau, J., Chedrawy, E., Eliopoulos, N., & Chiu, R. C. (2000). Marrow stromal cells for cellular cardiomyoplasty: feasibility and potential clinical advantages. The Journal of Thoracic and Cardiovascular Surgery, 120, 999–1005.

    Article  PubMed  CAS  Google Scholar 

  27. Lee, K. D., Kuo, T. K., Whang-Peng, J., et al. (2004). In vitro hepatic differentiation of human mesenchymal stem cells. Hepatology, 40, 1275–1284.

    Article  PubMed  CAS  Google Scholar 

  28. Izadpanah, R., Kaushal, D., Kriedt, C., et al. (2008). Long-term in vitro expansion alters the biology of adult mesenchymal stem cells. Cancer Research, 68(11), 4229–4238.

    Article  PubMed  CAS  Google Scholar 

  29. Izadpanah, R., Trygg, C., Patel, B., et al. (2006). Biologic properties of mesenchymal stem cells derived from bone marrow and adipose tissue. Journal of Cellular Biochemistry, 99, 1285–1297.

    Article  PubMed  CAS  Google Scholar 

  30. Jiang, Y., Jahagirdar, B. N., Reinhardt, R. L., et al. (2002). Pluripotency of mesenchymal stem cells derived from adult marrow. Nature, 418(6893), 41–49.

    Article  PubMed  CAS  Google Scholar 

  31. Bonab, M. M., Alimoghaddam, K., Talebian, F., Ghaffari, S. H., Ghavamzadeh, A., & Nikbin, B. (2006). Aging of mesenchymal stem cell in vitro. BMC Cell Biology, 7, 14.

    Article  PubMed  CAS  Google Scholar 

  32. Muraglia, A., Cancedda, R., & Quarto, R. (2000). Clonal mesenchymal progenitors from human bone marrow differentiate in vitro according to a hierarchical model. Journal of Cell Science, 113(Pt. 7), 1161–1166.

    PubMed  CAS  Google Scholar 

  33. Banfi, A., Muraglia, A., Dozin, G., Mastrogiacomo, M., Cancedda, R., & Quarto, R. (2000). Proliferation kinetics and differentiation potential of ex vivo expanded human bone marrow stromal cells: implications for their use in cell therapy. Experimental Hematology, 28, 707–715.

    Article  PubMed  CAS  Google Scholar 

  34. Bruder, S. P., Jaiswal, N., & Haynesworth, S. E. (1997). Growth kinetics, self-renewal, and the osteogenic potential of purified human mesenchymal stem cells during extensive subcultivation and following cryopreservation. Journal of Cellular Biochemistry, 64, 278–294.

    Article  PubMed  CAS  Google Scholar 

  35. Baxter, M. A., Wynn, R. F., Jowitt, S. N., Wraith, J. E., Fairbairn, L. J., & Bellantuono, I. (2004). Study of telomere length reveals rapid aging of human marrow stromal cells following in vitro expansion. Stem Cells, 22, 675–682.

    Article  PubMed  CAS  Google Scholar 

  36. Tan, Q., Rui, Y. F., Lee, Y. W., & Lui, P. P. Y. (2011). Effect of in vitro passages on the biological properties of tendon-derived stem cells (TDSCs)—Implication in musculoskeletal tissue engineering. In Proceedings of International Symposium of Ligament and Tendon (ISL&T) XI, 12th January, 2011, Long Beach, California, USA.

  37. Levesque, J. P., Helwani, F. M., & Winkler, I. G. (2010). The endosteal ‘osteoblastic’ niche and its role in hematopoietic stem cell homing and mobilization. Leukemia, 24(12), 1979–1992.

    Article  PubMed  Google Scholar 

  38. Zhang, J., & Wang, J. H. C. (2010). Mechanical response of tendon stem cells: implications of tendon homeostasis and pathogenesis of tendinopathy. Journal of Orthopaedic Research, 28(5), 639–643.

    PubMed  Google Scholar 

  39. Wang, J. C., & Thampatty, B. P. (2008). Mechanobiology of adult of stem cells. International Review of Cell and Molecular Biology, 271, 297–342.

    Article  CAS  Google Scholar 

  40. Chuen, F. S., Chuk, C. Y., Ping, W. Y., Nar, W. W., Kim, H. L., & Ming, C. K. (2004). Immunohistochemical characterization of cells in adult human patella tendons. Journal of Histochemisty & Cytochemistry, 52(9), 1151–1157.

    Article  CAS  Google Scholar 

  41. Yoshizawa, T., Takizawa, F., Iizawa, F., et al. (2004). Homeobox protein MSX2 acts as a molecular defense mechanism for preventing ossification in ligament fibroblasts. Molecular and Cellular Biology, 24, 3460–3472.

    Article  PubMed  CAS  Google Scholar 

  42. Hoffmann, A., Pelled, G., Turgeman, G., et al. (2006). Neotendon formation induced by manipulation of the Smad8 signalling pathway in mesenchymal stem cells. Journal of Clinical Investigation, 116, 940–952.

    Article  PubMed  CAS  Google Scholar 

  43. McNeilly, C. M., Banes, A. J., Benjamin, M., & Ralphs, J. R. (1996). Tendon cells in vivo form a three dimensional network of cell processes linked by gap junctions. Journal of Anatomy, 189(Pt 3), 593–600.

    PubMed  Google Scholar 

  44. Luo, Q., Song, G., Song, Y., Xu, B., Qin, J., & Shi, Y. (2009). Indirect co-culture with tenocytes promotes proliferation and mRNA expression of tendon/ligament related genes in rat bone marrow mesenchymal stem cells. Cytotechnology, 61(1–2), 1–10.

    Article  PubMed  Google Scholar 

  45. Crisan, M., Yap, S., Casteilla, L., et al. (2008). A perivascular origin for mesenchymal stem cells in multiple human organs. Cell Stem Cell, 3(11), 301–313.

    Article  PubMed  CAS  Google Scholar 

  46. Caplan, A. I. (2008). All MSCs are pericytes? Cell Stem Cell, 3(3), 229–230.

    Article  PubMed  CAS  Google Scholar 

  47. da Silva Meirelles, L., Chagastelles, P. C., & Nardi, N. B. (2006). Mesenchymal stem cells reside in virtually all post-natal organs and tissues. Journal of Cell Science, 119(Pt 11), 2204–2213.

    Article  PubMed  CAS  Google Scholar 

  48. Tempfer, H., Wagner, A., Gehwolf, R., et al. (2009). Perivascular cells of the supraspinatus tendon express both tendon- and stem cell-related markers. Histochemistry and Cell Biology, 131, 733–741.

    Article  PubMed  CAS  Google Scholar 

  49. Helm, G. A., Li, J. Z., Alden, T. D., et al. (2001). A light and electron microscopic study of ectopic tendon and ligament formation induced by bone morphogenetic protein-13 adenoviral gene therapy. Journal of Neurosurgery, 95, 298–307.

    Article  PubMed  CAS  Google Scholar 

  50. Wong, Y. P., Fu, S. C., Cheuk, Y. C., Lee, K. M., Wong, M. W., & Chan, K. M. (2005). Bone morphogenetic protein 13 stimulates cell proliferation and production of collagen in human patellar tendon fibroblasts. Acta Orthopaedica, 76(3), 421–427.

    PubMed  Google Scholar 

  51. Theobald, P., Benjamin, M., Nokes, L., & Pugh, N. (2005). Review of the vascularisation of the human Achilles tendon. Injury, 36(11), 1267–1272.

    Article  PubMed  CAS  Google Scholar 

  52. Arnoczky, S. P., Lavagnino, M., & Egerbacher, M. T. (2007). The response of tendon cells to changing loads: Implications in the etiopathogenesis of tendinopathy. In S. L. Y. Woo, P. A. F. H. Renstrom, & S. P. Arnoczky (Eds.), Tendinopathy in athletes (pp. 46–59). USA: Blackwell.

    Chapter  Google Scholar 

  53. Riley, G. P., Harrall, R. L., Constant, C. R., Cawston, T. E., & Hazlman, B. L. (1996). Prevalence and possible pathological significance of calcium phosphate salt accumulation in tendon matrix degeneration. Annals of the Rheummatic Diseases, 55, 109–115.

    Article  CAS  Google Scholar 

  54. Fu, S. C., Chan, B. P., Wang, W., Pau, H. M., Chan, K. M., & Rolf, C. G. (2002). Increase expression of matrix metalloproteinase 1(MMP1) in 11 patients with patellar tendinosis. Acta Orthopaedica Scandinavica, 73(6), 658–662.

    Article  PubMed  Google Scholar 

  55. Fu, S. C., Wang, W., Pau, H. M., Wong, Y. P., Chan, K. M., & Rolf, C. G. (2002). Increased expression of transforming growth factor-beta1 in patellar tendinosis. Clinical Orthopaedics and Related Research, 400, 174–183.

    Article  PubMed  Google Scholar 

  56. Jones, G. C., Corps, A. N., Pennington, C. J., et al. (2006). Expression profiling of metalloproteinases and tissue inhibitors of metalloproteinases in normal and degenerate human Achilles tendon. Arthritis & Rheumatism, 54(3), 832–842.

    Article  CAS  Google Scholar 

  57. Maffulli, N., Reaper, J., Ewen, S. W. B., Waterston, S. W., & Barrass, V. (2006). Chondral metaplasia in calcific tendinopathy of the Achilles tendon. Clinical Journal of Sport Medicine, 16, 329–334.

    Article  PubMed  Google Scholar 

  58. Karousou, E., Ronga, M., Vigetti, D., Passi, A., & Maffulli, N. (2008). Collagens, proteoglycans, MMP-2, MMP-9 and TIMPs in human Achilles tendon rupture. Clinical Orthopaedics and Related Research, 466, 1577–1582.

    Article  PubMed  Google Scholar 

  59. Karousou, E., Ronga, M., Vigetti, D., Passi, A., & Maffulli, N. (2010). Molecular interactions in extracellular matrix of tendon. Frontiers in Bioscience (Elite Edition), 2, 1–12.

    Article  Google Scholar 

  60. Fu, S. C., Chan, K. M., & Rolf, C. G. (2007). Increased deposition of sulfated glycosaminoglycans in human patellar tendinopathy. Clinical Journal of Sport Medicine, 17(2), 129–134.

    Article  PubMed  Google Scholar 

  61. Fenwick, S., Harrall, R., Hackney, R., et al. (2002). Endochondral ossification in Achilles and patella tendinopathy. Rheumatology (Oxford), 41, 474–476.

    Article  CAS  Google Scholar 

  62. Rui, Y. F., Lui, P. P. Y., Chan, L. S., Chan, K. M., Fu, S. C., & Li, G. (2011). Does erroneous differentiation of tendon-derived stem cells contribute to the pathogenesis of calcifying tendinopathy? Chinese Medical Journal (English), 124(4), 606–610.

    Google Scholar 

  63. Lui, P. P. Y., Fu, S. C., Chan, L. S., Hung, L. K., & Chan, K. M. (2009). Chondrocyte phenotype and ectopic ossification in collagenase-induced tendon degeneration. Journal of Histochemistry & Cytochemistry, 57(2), 91–100.

    Article  CAS  Google Scholar 

  64. Rui, Y. F., Lui, P. P. Y., Wong, Y. M., et al. (2011). Impaired differentiation and proliferation of tendon-derived stem cells (TDSCs) isolated from collagenase-induced tendon injury model—A potential mechanism for the chondro-ossification and failed healing tendinopathy. In Proceedings of 57th Annual Meeting of the Orthopaedic Research Society, 13th–16th January, 2011, Long Beach, California, USA.

  65. Archambault, J. M., Jelinsky, S. A., Lake, S. P., Hill, A. A., Glaser, D. L., & Soslowsky, L. J. (2007). Rat supraspinatus tendon expresses cartilage markers with overuse. Journal of Orthopaedic Research, 25, 617–624.

    Article  PubMed  CAS  Google Scholar 

  66. Clegg, P. D., Strassburg, S., & Smith, R. K. (2007). Cell phenotypic variation in normal and damaged tendons. International Journal of Experimental Pathology, 88, 227–235.

    Article  PubMed  Google Scholar 

  67. Speer, M. Y., Yang, H. Y., Brabb, T., et al. (2009). Smooth muscle cells give rise to osteochondrogenic precursors and chondrocytes in calcifying arteries. Circulation Research, 104(6), 733–741.

    Article  PubMed  CAS  Google Scholar 

  68. Kim, S. Y., Choi, H. Y., Myung, K. B., & Choi, Y. W. (2008). The expression of molecular mediators in the idiopathic cutaneous calcification and ossification. Journal of Cutaneous Pathology, 35(9), 826–831.

    Article  PubMed  Google Scholar 

  69. Lounev, V. Y., Ramachandran, R., Wosczyna, M. N., et al. (2009). Identification of progenitor cells that contribute to heterotopic skeletogenesis. The Journal of Bone and Joint Surgery American, 91(3), 652–663.

    Article  Google Scholar 

  70. Bajada, S., Marshall, M. J., Wright, K. T., Richardson, J. B., & Johnson, W. E. (2009). Decreased osteogenesis, increased cell senescence and elevated Dickkopf-1 secretion in human fracture nonunion stromal cells. Bone, 45(4), 726–735.

    Article  PubMed  CAS  Google Scholar 

  71. Langberg, H., Skovgaard, D., Karamouzis, M., Bulow, J., & Kjaer, M. (1999). Metabolism and inflammatory mediators in the peritendinous space measured by microdialysis during intermittent isometric exercise in humans. The Journal of Physiology, 515(Pt 3), 919–927.

    Article  PubMed  CAS  Google Scholar 

  72. Zhang, J., & Wang, J. H. (2010). Production of PGE(2) increases in tendons subjected to repetitive mechanical loading and induces differentiation of tendon stem cells into non-tenocytes. Journal of Orthopaedic Research, 28(2), 198–203.

    PubMed  Google Scholar 

  73. Kuo, C. K., & Tuan, R. S. (2008). Mechanoactive tenogenic differentiation of human mesenchymal stem cells. Tissue Engineering Part A, 14(10), 1615–1627.

    Article  PubMed  CAS  Google Scholar 

  74. Almekinders, L. C., Banes, A. J., & Ballenger, C. A. (1993). Effects of repetitive motion on human fibroblasts. Medicine & Science in Sports & Exercise, 25, 603–607.

    CAS  Google Scholar 

  75. Wang, J. H., Jia, F., Yang, G., et al. (2003). Cyclic mechanical stretching of human tendon fibroblasts increases the production of prostaglandin E(2) and levels of cyclooxygenase expression: a novel in vitro model study. Connective Tissue Research, 44, 128–133.

    PubMed  CAS  Google Scholar 

  76. Rodeo, S. A., Suzuki, K., Deng, X. H., Wozney, J., & Warren, R. F. (1999). Use of recombinant human bone morphogenetic protein-2 to enhance tendon healing in a bone tunnel. American Journal of Sports Medicine, 27, 476–488.

    PubMed  CAS  Google Scholar 

  77. Ma, C. B., Kawamura, S., Deng, X. H., et al. (2007). Bone morphogenetic proteins-signaling plays a role in tendon-to-bone healing: a study of rhBMP-2 and noggin. American Journal of Sports Medicine, 35, 597–604.

    Article  PubMed  Google Scholar 

  78. Tang, Y., Tang, W., Lin, Y., et al. (2008). Combination of bone tissue engineering and BMP-2 gene transfection promotes bone healing in osteoporotic rats. Cell Biology International, 32, 1150–1157.

    Article  PubMed  CAS  Google Scholar 

  79. Martinek, V., Latterman, C., Usas, A., et al. (2002). Enhancement of tendon-bone integration of anterior cruciate ligament grafts with bone morphogenetic protein-2 gene transfer: a histological and biomechanical study. Journal of Bone & Joint Surgery American, 84, 1123–1131.

    Google Scholar 

  80. Chen, C. H., Liu, H. W., Tsai, C. L., Yu, C. M., Lin, I. H., & Hsiue, G. H. (2008). Photoencapsulation of bone morphogenetic protein-2 and periosteal progenitor cells improve tendon graft healing in a bone tunnel. American Journal of Sports Medicine, 36, 461–473.

    PubMed  Google Scholar 

  81. Jiang, Y., Chen, L. K., Zhu, D. C., et al. (2010). The inductive effect of bone morphogenetic protein-4 on chondral-lineage differentiation and in situ cartilage repair. Tissue Engineering Part A, 16(5), 1621–1632.

    Article  PubMed  CAS  Google Scholar 

  82. Neuwirth, J., Fuhrmann, R. A. E., Veit, A., et al. (2006). Expression of bioactive bone morphogenetic proteins in the subacromial bursa of patients with chronic degeneration of the rotator cuff. Arthritis Research & Therapy, 8, R92.

    Article  CAS  Google Scholar 

  83. Sato, R., Uchida, K., Kobayashi, S., et al. (2007). Ossification of the posterior longitudinal ligament of the cervical spine: histopathological findings around the calcification and ossification front. Journal of Neurosurgery: Spine, 7, 174–183.

    Article  PubMed  Google Scholar 

  84. Li, H., Jiang, L. S., & Dai, L. Y. (2007). Hormones and growth factors in the pathogenesis of spinal ligament ossification. European Spine Journal, 16, 1075–1084.

    Article  PubMed  Google Scholar 

  85. Tanno, M., Furukawa, K. I., Ueyama, K., Harata, S., & Motomura, S. (2003). Uniaxial cyclic stretch induces osteogenic differentiation and synthesis of bone morphogenetic proteins of spinal ligament cells derived from patients with ossification of the posterior longitudinal ligaments. Bone, 33, 475–484.

    Article  PubMed  CAS  Google Scholar 

  86. Lui, P. P. Y., Chan, L. S., Cheuk, Y. C., Lee, Y. W., & Chan, K. M. (2009). Expression of bone morphogenetic protein-2 in the chondrogenic and ossifying sites of calcific tendinopathy and traumatic tendon injury rat models. Journal of Orthopaedic Surgery and Research, 21(4), 27.

    Article  Google Scholar 

  87. Yee Lui, P. P., Wong, Y. M., Rui, Y. F., Lee, Y. W., Chan, L. S., & Chan, K. M. (2011). Expression of osteogenic BMPs in calcified failed tendon healing model of tendinopathy. Journal of Orthopaedic Research, 29(6): 816–821.

    Google Scholar 

  88. Rui, Y. F., Lui, P. P. Y., Rolf, C. G., Wong, Y. M., Lee, Y. W., & Chan, K M. (2011). Expression of chondro-osteogenic BMPs in clinical samples of calcifying and uncalcifying patellar tendinopathy—A histopathological study. In Proceedings of International Symposium of Ligament and Tendon (ISL&T) XI, 12th January, 2011, Long Beach, California, USA.

  89. Csiszar, A., Smith, K. E., Koller, A., Kaley, G., Edwards, J. G., & Ungvari, Z. (2005). Regulation of bone morphogenetic protein-2 expression in endothelial cells: role of nuclear factor-kappaB activation by tumor necrosis factor-alpha, H2O2, and high intra-vascular pressure. Circulation, 111, 2364–2372.

    Article  PubMed  CAS  Google Scholar 

  90. Csiszar, A., Labinskyy, N., Smith, K. E., et al. (2007). Downregulation of bone morphogenetic protein 4 expression in coronary arterial endothelial cells-Role of shear stress and the cAMP/protein kinase A pathway. Arteriosclerosis, Thrombosis, and Vascular Biology, 27, 776–782.

    Article  PubMed  CAS  Google Scholar 

  91. Rath, B., Nam, J., Knobloch, T. J., Lannutti, J. J., & Agarwal, S. (2008). Compressive forces induce osteogenic gene expression in calvarial osteoblasts. Journal of Biomechanics, 41(5), 1095–1103.

    Article  PubMed  Google Scholar 

  92. Lui, P. P. Y., Chan, L. S., Lee, Y. W., Fu, S. C., & Chan, K. M. (2010). Sustained expression of proteoglycans and collagen type III / Type I ratio in a calcified tendinopathy model. Rheumatology, 49(2), 231–239.

    Article  PubMed  CAS  Google Scholar 

  93. Seib, F. P., Franke, M., Jing, D., Werner, C., & Bornhauser, M. (2009). Endogenous bone morphogenetic proteins in human bone marrow-derived multipotent mesenchymal stromal cells. European Journal of Cell Biology, 88, 257–271.

    Article  PubMed  CAS  Google Scholar 

  94. Lui, P. P. Y., Chan, L. S., Fu, S. C., & Chan, K. M. (2010). Expression of sensory neuropeptides in tendon is associated with failed healing and activity-related tendon pain in collagenase-induced tendon injury. American Journal of Sports Medicine, 38(4), 757–764.

    Article  PubMed  Google Scholar 

  95. Shih, C., & Bernard, G. W. (1997). Neurogenic substance P stimulates osteogenesis in vitro. Peptides, 18, 323–326.

    Article  PubMed  CAS  Google Scholar 

  96. Xu, Y., & Murrell, G. A. (2008). The basic science of tendinopathy. Clinical Orthopaedics and Related Research, 466, 1528–1538.

    Article  PubMed  Google Scholar 

  97. Tsuzaki, M., Bynum, D., Almekinders, L., Yang, X., Faber, J., & Banes, A. J. (2003). ATP modulates load-inducible IL-1beta, COX2, and MMP-3 gene expression in human tendon cells. Journal of Cellular Biochemistry, 89(3), 556–562.

    Article  PubMed  CAS  Google Scholar 

  98. Wang, J. H., Jia, F., Yang, G., et al. (2003). Cyclic mechanical stretching of human tendon fibroblasts increases the production of prostaglandin E2 and levels of cyclooxygenase expression: a novel in vitro model study. Connective Tissue Research, 44(3–4), 128–133.

    PubMed  CAS  Google Scholar 

  99. Riley, G. (2004). The pathogenesis of tendinopathy. A molecular perspective. Rheumatology (Oxford), 43(2), 131–142.

    Article  CAS  Google Scholar 

  100. Gotoh, M., Hamada, K., Yamakawa, H., Inoue, A., & Fukuda, H. (1998). Increased substance P in subacromial bursa and shoulder pain in rotator cuff diseases. Journal of Orthopaedic Research, 16(8), 618–621.

    Article  PubMed  CAS  Google Scholar 

  101. Lian, O., Dahl, J., Ackermann, P. W., Frihagen, F., Engebretsen, I., & Bahr, R. (2006). Pronociceptive and antinociceptive neuromediators in patellar tendinopathy. American Journal of Sports Medicine, 34, 1801–1808.

    Article  PubMed  Google Scholar 

  102. Schubert, T. E., Weidler, C., Lerch, K., Hofstadter, F., & Straub, R. H. (2005). Achilles tendinosis is associated with sprouting of substance P positive nerve fibers. Annals of the Rheumatic Diseases, 64, 1083–1086.

    Article  PubMed  CAS  Google Scholar 

  103. Lerner, U. H. (2002). Neuropeptidergic regulation of bone resorption and bone formation. Journal of Musculoskeletal & Neuronal Interactions, 2, 440–447.

    CAS  Google Scholar 

  104. Maffulli, N., Wong, J., & Almekinders, L. C. (2003). Types and epidemiology of tendinopathy. Clinics in Sports Medicine, 22(4), 675–692.

    Article  PubMed  Google Scholar 

  105. Butler, D. L., Juncosa, N., & Dressler, M. R. (2004). Functional efficacy of tendon repair processes. Annual Review of Biomedical Engineering, 6, 303–329.

    Article  PubMed  CAS  Google Scholar 

  106. Proctor, C. S., Jackson, D. W., & Simon, T. M. (1997). Characterization of the repair tissue after removal of the central one-third of the patellar ligament: an experimental study in a goat model. Journal of Bone and Joint Surgery American Volume, 79(7), 997–1006.

    CAS  Google Scholar 

  107. Hampson, K., Forsyth, N. R., El Haj, A., & Maffulli, N. (2008). Tendon tissue engineering. In N. Ashammakhi, R. Reis & F. Chiellini (Ed.), E-book: Topics in tissue engineering Vol 4 (chapter 3). http://www.oulu.fi/spareparts/ebook_topics_in_t_e_vol4/index.html

  108. Awad, H. A., Butler, D. L., Boivin, G. P., et al. (1999). Autologous mesenchymal stem cell-mediated repair of tendon. Tissue Engineering, 5(3), 267–277.

    Article  PubMed  CAS  Google Scholar 

  109. Awad, H. A., Butler, D. L., Dressler, M. R., Smith, F., Boivin, G. P., & Young, R. G. (2003). Repair of patellar tendon injuries using mesenchymal stem cells and collagen scaffolds. Journal of Orthopaedic Research, 21(3), 420–431.

    Article  PubMed  CAS  Google Scholar 

  110. Young, R. G., Butler, D. L., Weber, W., Caplan, A. I., Gordon, S. L., & Fink, D. J. (1998). Use of mesenchymal stem cells in a collagen matrix for Achilles tendon repair. Journal of Orthopaedic Research, 16(4), 406–413.

    Article  PubMed  CAS  Google Scholar 

  111. Ouyang, H. W., Goh, J. C., Thambyah, A., Teoh, S. H., & Le, E. H. (2003). Knitted poly-lactide-co-glycolide scaffold loaded with bone marrow stromal cells in repair and regeneration of rabbit Achilles tendon. Tissue Engineering, 9(3), 431–439.

    Article  PubMed  CAS  Google Scholar 

  112. Kryger, G. S., Chong, A. K., Costa, M., Pham, H., Bates, S. J., & Chang, J. A. (2007). Comparison of tenocytes and mesenchymal stem cells for use in flexor tendon tissue engineering. Journal of Hand Surgery American Volume, 32(5), 597–605.

    Article  Google Scholar 

  113. Juncosa-Melvin, N., Boivin, G. P., Galloway, M. T., Gooch, C., West, J. R., Sklenka, A. M., et al. (2005). Effects of cell-to-collagen ratio in mesenchymal stem cell-seeded implants on tendon repair biomechanics and histology. Tissue Engineering, 11(3–4), 448–457.

    Article  PubMed  CAS  Google Scholar 

  114. Juncosa-Melvin, N., Boivin, G. P., Gooch, C., et al. (2006). The effect of autologous mesenchymal stem cells on the biomechanics and histology of gel-collagen sponge constructs used for rabbit patellar tendon repair. Tissue Engineering, 12(2), 369–379.

    Article  PubMed  CAS  Google Scholar 

  115. Chong, A. K., Ang, A. D., Goh, J. C., Hui, J. H., Lim, A. Y., Lee, E. H., et al. (2007). Bone marrow-derived mesenchymal stem cells influence early tendon-healing in a rabbit Achilles tendon model. Journal of Bone and Joint Surgery American Volume, 89(1), 74–81.

    Article  Google Scholar 

  116. Hankemeier, S., van Griensven, M., Ezechieli, M., et al. (2007). Tissue engineering of tendons and ligaments by human bone marrow stromal cells in a liquid fibrin matrix in immunodeficient rats: results of a histologic study. Archives of Orthopaedic and Trauma Surgery, 127(9), 815–821.

    Article  PubMed  Google Scholar 

  117. Chen, X., Song, X., Yin, Z., et al. (2009). Stepwise differentiation of human embryonic stem cells promotes tendon regeneration by secreting fetal tendon matrix and differentiation factors. Stem Cells, 27(6), 1276–1287.

    Article  PubMed  CAS  Google Scholar 

  118. Harris, M. T., Butler, D. L., Boivin, G. P., Florer, J. B., Schantz, E. J., & Wenstrup, R. J. (2004). Mesenchymal stem cells used for rabbit tendon repair can form ectopic bone and express alkaline phosphatase activity in constructs. Journal of Orthopaedic Research, 22(5), 998–1003.

    Article  PubMed  CAS  Google Scholar 

  119. Tasso, R., Augell, A., Carida, M., et al. (2009). Development of sacromas in mice implanted with mesenchymal stem cells seeded onto bioscaffolds. Carcinogenesis, 30(1), 150–157.

    Article  PubMed  CAS  Google Scholar 

  120. Sakaguchi, Y., Sekiya, I., Yagishita, K., & Muneta, T. (2005). Comparison of human stem cells derived from various mesenchymal tissues: superiority of synovium as a cell source. Arthritis & Rheumatism, 52(8), 2521–2529.

    Article  Google Scholar 

  121. Deans, T. L., & Elisseeff, J. H. (2009). Stem cells in musculoskeletal engineered tissue. Current Opinion in Biotechnology, 20, 537–544.

    Article  PubMed  CAS  Google Scholar 

  122. Baksh, D., Yao, R., & Tuan, R. S. (2007). Comparison of proliferative and multilineage differentiation potential of human mesenchymal stem cells derived from umbilical cord and bone marrow. Stem Cells, 25, 1384–1392.

    Article  PubMed  CAS  Google Scholar 

  123. Hayashi, O., Katsube, Y., Hirose, M., Ohgushi, H., & Ito, H. (2008). Comparison of osteogenic ability of rat mesenchymal stem cells from bone marrow, periosteum, and adipose tissue. Calcified Tissue International, 82, 238–247.

    Article  PubMed  CAS  Google Scholar 

  124. Lin, L., Shen, Q., Wei, X., et al. (2009). Comparison of osteogenic potentials of BMP4 transduced stem cells from autologous bone marrow and fat tissue in a rabbit model of calvarial defects. Calcified Tissue International, 85, 55–65.

    Article  PubMed  CAS  Google Scholar 

  125. Singh, S., Dhaliwal, N., Crawford, R., & Xiao, Y. (2009). Cellular senescence and longevity of osteophyte-derived mesenchymal stem cells compared to patient-matched bone marrow stromal cells. Journal of Cellular Biochemistry, 108, 839–850.

    Article  PubMed  CAS  Google Scholar 

  126. Wang, L., Tran, I., Seshareddy, K., Weiss, M. L., & Detamore, M. S. (2009). A comparison of human bone marrow-derived mesenchymal stem cells and human umbilical cord-derived mesenchymal stromal cells for cartilage tissue engineering. Tissue Engineering Part A, 15(8), 2259–2266.

    Article  PubMed  CAS  Google Scholar 

  127. Kolambkar, Y. M., Peister, A., Soker, S., Atala, A., & Guldberg, R. E. (2007). Chondrogenic differentiation of amniotic fluid-derived stem cells. Journal of Molecular Histology, 38, 405–413.

    Article  PubMed  CAS  Google Scholar 

  128. Kern, S., Eichler, H., Stoeve, J., Kluter, H., & Bieback, K. (2006). Comparative analysis of mesenchymal stem cells from bone marrow, umbilical cord blood, or adipose tissue. Stem Cells, 24, 1294–1301.

    Article  PubMed  CAS  Google Scholar 

  129. Cheng, M. T., Liu, C. L., Chen, T. H., & Lee, O. K. (2010). Comparison of potentials between stem cells isolated from human anterior cruciate ligament and bone marrow for ligament tissue engineering. Tissue Engineering Part A, 16(7), 2237–2235.

    Article  PubMed  CAS  Google Scholar 

  130. Yoshimura, H., Muneta, T., Nimura, A., Yokoyama, A., & Koga, H. (2007). Comparison of rat mesenchymal stem cells derived from bone marrow, synovium periosteum, adipose tissue, and muscle. Cell and Tissue Research, 327, 449–462.

    Article  PubMed  CAS  Google Scholar 

  131. Matsubara, T., Tsutsumi, S., Pan, H., et al. (2004). A new technique to expand human mesenchymal stem cells using basement membrane extracellular matrix. Biochemical and Biophysical Research Communications, 313, 503–508.

    Article  PubMed  CAS  Google Scholar 

  132. Lui, P. P. Y., Rui, Y. F., Ni, M., et al. (2011). Comparison of potentials of stem cells isolated from tendon and bone marrow for musculoskeletal tissue engineering. In Proceedings of 57th Annual Meeting of the Orthopaedic Research Society, 13th–16th January, 2011, Long Beach, California, USA.

  133. Ni, M., Lui, P. P. Y., Rui, Y. F., et al. (2011). Allogenic Tendon-derived stem cells (TDSCs) promoted tendon regeneration. In Proceedings of 57th Annual Meeting of the Orthopaedic Research Society, 13th–16th January, 2011, Long Beach, California, USA.

  134. Ni, M., Lui, P. P. Y., Rui, Y. F., et al. (2011). Tendon-derived stem cell (TDSC): A better stem cell source compared to bone marrow-derived mesenchymal stem cell (BMSC) for tendon regeneration? In Proceedings of International Symposium of Ligament and Tendon (ISL&T) XI, 12th January, 2011, Long Beach, California, USA.

Download references

Acknowledgement

This work was supported by resources donated by the Hong Kong Jockey Club Charities Trust.

Disclosures

The authors indicate no potential conflicts of interest.

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Pauline Po Yee Lui.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Lui, P.P.Y., Chan, K.M. Tendon-Derived Stem Cells (TDSCs): From Basic Science to Potential Roles in Tendon Pathology and Tissue Engineering Applications. Stem Cell Rev and Rep 7, 883–897 (2011). https://doi.org/10.1007/s12015-011-9276-0

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s12015-011-9276-0

Keywords

Navigation