Abstract
The repair of tendon and ligament injuries or even entire joint replacements after trauma, inflammation, or degeneration still presents a major clinical challenge to orthopaedic medicine. Soft tissues like cartilage, tendons and ligaments are poorly vascularized and heal slowly. In addition, healing often leads to the formation of fibrous, scarry tissue which lacks the original flexibility and biomechanical properties. Tendon-to-bone healing is a rather slow process and involves complex biological activities between these nonhomogenous soft and hard tissues. We will here review recent progress in the management of musculo-skeletal disorders of the joints specifically focussing on stem cell-dependent approaches for the repair of tendon-to-bone junctions.
This is a preview of subscription content, log in via an institution.
Buying options
Tax calculation will be finalised at checkout
Purchases are for personal use only
Learn about institutional subscriptionsReferences
Bedi A, Kovacevic D, Hettrich C, Gulotta LV, Ehteshami JR, Warren RF, Rodeo SA (2010) The effect of matrix metalloproteinase inhibition on tendon-to-bone healing in a rotator cuff repair model. J Shoulder Elbow Surg 19:384–391
Benjamin M, Kumai T, Milz S, Boszczyk BM, Boszczyk AA, Ralphs JR (2002) The skeletal attachment of tendons – tendon “entheses”. Comp Biochem Physiol A Mol Integr Physiol 133:931–945
Benjamin M, Moriggl B, Brenner E, Emery P, McGonagle D, Redman S (2004) The “enthesis organ” concept: why enthesopathies may not present as focal insertional disorders. Arthritis Rheum 50:3306–3313
Bi Y, Ehirchiou D, Kilts TM, Inkson CA, Embree MC, Sonoyama W, Li L, Leet AI, Seo BM, Zhang L, Shi S, Young MF (2007) Identification of tendon stem/progenitor cells and the role of the extracellular matrix in their niche. Nat Med 13:1219–1227
Blitz E, Viukov S, Sharir A, Shwartz Y, Galloway JL, Pryce BA, Johnson RL, Tabin CJ, Schweitzer R, Zelzer E (2009) Bone ridge patterning during musculoskeletal assembly is mediated through SCX regulation of Bmp4 at the tendon-skeleton junction. Dev Cell 17:861–873
Brent AE, Schweitzer R, Tabin CJ (2003) A somitic compartment of tendon progenitors. Cell 113:235–248
Crisan M, Yap S, Casteilla L, Chen CW, Corselli M, Park TS, Andriolo G, Sun B, Zheng B, Zhang L, Norotte C, Teng PN, Traas J, Schugar R, Deasy BM, Badylak S, Buhring HJ, Giacobino JP, Lazzari L, Huard J, Peault B (2008) A perivascular origin for mesenchymal stem cells in multiple human organs. Cell Stem Cell 3:301–313
Demirag B, Sarisozen B, Ozer O, Kaplan T, Ozturk C (2005) Enhancement of tendon-bone healing of anterior cruciate ligament grafts by blockage of matrix metalloproteinases. J Bone Joint Surg Am 87:2401–2410
Friedenstein AJ, Piatetzky-Shapiro II, Petrakova KV (1966) Osteogenesis in transplants of bone marrow cells. J Embryol Exp Morphol 16:381–390
Gulotta LV, Kovacevic D, Ying L, Ehteshami JR, Montgomery S, Rodeo SA (2008) Augmentation of tendon-to-bone healing with a magnesium-based bone adhesive. Am J Sports Med 36:1290–1297
Gulotta LV, Kovacevic D, Ehteshami JR, Dagher E, Packer JD, Rodeo SA (2009) Application of bone marrow-derived mesenchymal stem cells in a rotator cuff repair model. Am J Sports Med 37:2126–2133
Gulotta LV, Kovacevic D, Montgomery S, Ehteshami JR, Packer JD, Rodeo SA (2010) Stem cells genetically modified with the developmental gene MT1-MMP improve regeneration of the supraspinatus tendon-to-bone insertion site. Am J Sports Med 38:1429–1437
Gulotta LV, Kovacevic D, Packer JD, Deng XH, Rodeo SA (2011) Bone marrow-derived mesenchymal stem cells transduced with scleraxis improve rotator cuff healing in a rat model. Am J Sports Med 39:1282–1289
Hoffmann A, Pelled G, Turgeman G, Eberle P, Zilberman Y, Shinar H, Keinan-Adamsky K, Winkel A, Shahab S, Navon G, Gross G, Gazit D (2006) Neotendon formation induced by manipulation of the Smad8 signalling pathway in mesenchymal stem cells. J Clin Invest 116:940–952
Holmbeck K, Bianco P, Caterina J, Yamada S, Kromer M, Kuznetsov SA, Mankani M, Robey PG, Poole AR, Pidoux I, Ward JM, Birkedal-Hansen H (1999) MT1-MMP-deficient mice develop dwarfism, osteopenia, arthritis, and connective tissue disease due to inadequate collagen turnover. Cell 99:81–92
Ju YJ, Muneta T, Yoshimura H, Koga H, Sekiya I (2008) Synovial mesenchymal stem cells accelerate early remodeling of tendon-bone healing. Cell Tissue Res 332:469–478
Knese H, Biermann H (1958) Knochenbildung an Sehnen- und Bandansätzen im Bereich ursprünglich chondraler Apophysen. Z Zellforsch 49:142–187
Lejard V, Blais F, Guerquin MJ, Bonnet A, Bonnin MA, Havis E, Malbouyres M, Bidaud CB, Maro G, Gilardi-Hebenstreit P, Rossert J, Ruggiero F, Duprez D (2011) EGR1 and EGR2 involvement in vertebrate tendon differentiation. J Biol Chem 286:5855–5867
Lim JK, Hui J, Li L, Thambyah A, Goh J, Lee EH (2004) Enhancement of tendon graft osteointegration using mesenchymal stem cells in a rabbit model of anterior cruciate ligament reconstruction. Arthroscopy 20:899–910
Liu W, Watson SS, Lan Y, Keene DR, Ovitt CE, Liu H, Schweitzer R, Jiang R (2010) The atypical homeodomain transcription factor Mohawk controls tendon morphogenesis. Mol Cell Biol 30:4797–4807
Lu H, Qin L, Cheung W, Lee K, Wong W, Leung K (2008) Low-intensity pulsed ultrasound accelerated bone-tendon junction healing through regulation of vascular endothelial growth factor expression and cartilage formation. Ultrasound Med Biol 34:1248–1260
Lui P, Zhang P, Chan K, Qin L (2010) Biology and augmentation of tendon-bone insertion repair. J Orthop Surg Res 5:59
Meirelles LS, Fontes AM, Covas DT, Caplan AI (2009) Mechanisms involved in the therapeutic properties of mesenchymal stem cells. Cytokine Growth Factor Rev 20:419–427
Mendez-Ferrer S, Michurina TV, Ferraro F, Mazloom AR, Macarthur BD, Lira SA, Scadden DT, Ma’ayan A, Enikolopov GN, Frenette PS (2010) Mesenchymal and haematopoietic stem cells form a unique bone marrow niche. Nature 466:829–834
Moffat KL, Sun WH, Pena PE, Chahine NO, Doty SB, Ateshian GA, Hung CT, Lu HH (2008) Characterization of the structure-function relationship at the ligament-to-bone interface. Proc Natl Acad Sci USA 105:7947–7952
Murchison ND, Price BA, Conner DA, Keene DR, Olson EN, Tabin CJ, Schweitzer R (2007) Regulation of tendon differentiation by scleraxis distinguishes force-transmitting tendons from muscle-anchoring tendons. Development 134:2697–2708
Nourissat G, Diop A, Maurel N, Salvat C, Dumont S, Pigenet A, Gosset M, Houard X, Berenbaum F (2010) Mesenchymal stem cell therapy regenerates the native bone-tendon junction after surgical repair in a degenerative rat model. PLoS One 5:e12248
Ouyang HW, Goh JC, Lee EH (2004) Use of bone marrow stromal cells for tendon graft-to-bone healing: histological and immunohistochemical studies in a rabbit model. Am J Sports Med 32:321–327
Pendegrass CJ, Oddy MJ, Cannon SR, Briggs T, Goodship AE, Blunn GW (2004) A histomorphological study of tendon reconstruction to a hydroxyapatite-coated implant: regeneration of a neo-enthesis in vivo. J Orthop Res 22:1316–1324
Qin L, Wang L, Wong MW, Wen C, Wang G, Zhang G, Chan KM, Cheung WH, Leung KS (2010) Osteogenesis induced by extracorporeal shockwave in treatment of delayed osteotendinous junction healing. J Orthop Res 28:70–76
Riley G (2008) Tendinopathy–from basic science to treatment. Nat Clin Pract Rheumatol 4:82–89
Sacchetti B, Funari A, Michienzi S, Di CS, Piersanti S, Saggio I, Tagliafico E, Ferrari S, Robey PG, Riminucci M, Bianco P (2007) Self-renewing osteoprogenitors in bone marrow sinusoids can organize a hematopoietic microenvironment. Cell 131:324–336
Shahab-Osterloh S, Witte F, Hoffmann A, Winkel A, Laggies S, Neumann B, Seiffart V, Lindenmaier W, Gruber AD, Ringe J, Haupl T, Thorey F, Willbold E, Corbeau P, Gross G (2010) Mesenchymal stem cell-dependent formation of heterotopic tendon-bone insertions (osteotendinous junctions). Stem Cells 28:1590–1601
Sharma P, Maffulli N (2006) Biology of tendon injury: healing, modeling and remodeling. J Musculoskelet Neuronal Interact 6:181–190
Spalazzi JP, Doty SB, Moffat KL, Levine WN, Lu HH (2006) Development of controlled matrix heterogeneity on a triphasic scaffold for orthopedic interface tissue engineering. Tissue Eng 12:3497–3508
Thomopoulos S, Zampiakis E, Das R, Silva MJ, Gelberman RH (2008) The effect of muscle loading on flexor tendon-to-bone healing in a canine model. J Orthop Res 26:1611–1617
Thomopoulos S, Genin GM, Galatz LM (2010) The development and morphogenesis of the tendon-to-bone insertion – what development can teach us about healing -. J Musculoskelet Neuronal Interact 10:35–45
Tormin A, Li O, Brune JC, Walsh S, Schutz B, Ehinger M, Ditzel N, Kassem M, Scheding S (2011) CD146 expression on primary non-hematopoietic bone marrow stem cells correlates to in situ localization. Blood 117:5067–5077
Wong MW, Qin L, Lee KM, Leung KS (2009) Articular cartilage increases transition zone regeneration in bone-tendon junction healing. Clin Orthop Relat Res 467:1092–1100
Yamazaki K, Allen TD (1990) Ultrastructural morphometric study of efferent nerve terminals on murine bone marrow stromal cells, and the recognition of a novel anatomical unit: the “neuro-reticular complex”. Am J Anat 187:261–276
Acknowledgement
The authors gratefully acknowledge the discussions with A. Hoffmann, Department of Trauma Surgery, Medical School Hannover, Germany.
Author information
Authors and Affiliations
Corresponding author
Editor information
Editors and Affiliations
Rights and permissions
Copyright information
© 2012 Springer Science+Business Media B.V.
About this chapter
Cite this chapter
Seiffart, V., Laggies, S., Gross, G. (2012). Mesenchymal Stem Cell-Dependent Formation and Repair of Tendon-Bone Insertions. In: Hayat, M. (eds) Stem Cells and Cancer Stem Cells,Volume 3. Stem Cells and Cancer Stem Cells, vol 3. Springer, Dordrecht. https://doi.org/10.1007/978-94-007-2415-0_32
Download citation
DOI: https://doi.org/10.1007/978-94-007-2415-0_32
Published:
Publisher Name: Springer, Dordrecht
Print ISBN: 978-94-007-2414-3
Online ISBN: 978-94-007-2415-0
eBook Packages: Biomedical and Life SciencesBiomedical and Life Sciences (R0)