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Synovial mesenchymal stem cells accelerate early remodeling of tendon-bone healing

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Abstract

Tendon-bone healing is important for the successful reconstruction of the anterior cruciate ligament by using the hamstring tendon. Mesenchymal stem cells (MSCs) have attracted much interest because of their self-renewing potential and multipotentiality for possible clinical use. We previously reported that MSCs derived from synovium had a higher proliferation and differentiation potential than the other MSCs that we examined. The purpose of this study was to investigate the effect and mechanism of the implantation of the synovial MSCs on tendon-bone healing in rats. Half of the Achilles’ tendon grafts of rats were inserted into a bone tunnel from the tibial plateau to the tibial tuberosity with a suture-post fixation. The bone tunnel was filled with MSCs labeled with fluorescent marker DiI or without MSCs as the control. The tendon-bone interface was analyzed histologically, and collagen fibers were quantified. At 1 week, the tendon-bone interface was filled with abundant DiI-positive cells, and the proportion of collagen fiber area was significantly higher in the MSC group than in the control group. By 2 weeks, the proportion of oblique collagen fibers, which appeared to be Sharpey’s fibers, was significantly higher in the MSC group than in the control group. At 4 weeks, the interface tissue disappeared, and the implanted tendon appeared to attach to the bone directly in both groups. DiI-labeled cells could no longer be observed. Implantation of synovial MSCs into bone tunnel thus accelerated early remodeling of tendon-bone healing, as shown histologically.

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References

  • Al-Khaldi A, Al-Sabti H, Galipeau J, Lachapelle K (2003) Therapeutic angiogenesis using autologous bone marrow stromal cells: improved blood flow in a chronic limb ischemia model. Ann Thorac Surg 75:204–209

    Article  PubMed  Google Scholar 

  • Anderson K, Seneviratne AM, Izawa K, Atkinson BL, Potter HG, Rodeo SA (2001) Augmentation of tendon healing in an intraarticular bone tunnel with use of a bone growth factor. Am J Sports Med 29:689–698

    PubMed  CAS  Google Scholar 

  • Camargo FD, Chambers SM, Goodell MA (2004) Stem cell plasticity: from transdifferentiation to macrophage fusion. Cell Prolif 37:55–65

    Article  PubMed  CAS  Google Scholar 

  • Caplan AI, Dennis J (2006) Mesenchymal stem cells as trophic mediators. J Cell Biochem 98:1076–1084

    Article  PubMed  CAS  Google Scholar 

  • Caterson EJ, Li WJ, Nesti LJ, Albert T, Danielson K, Tuan RS (2002) Polymer/alginate amalgam for cartilagetissue engineering. Ann N Y Acad Sci 961:134–138

    Article  PubMed  CAS  Google Scholar 

  • Crawford JM, Braunwald NS (1991) Toxicity in vital fluorescence microscopy: effect of dimethylsulfoxide, rhodamine-123, and DiI-low density lipoprotein on fibroblast growth in vitro. In Vitro Cell Dev Biol 27A:633–638

    Article  PubMed  CAS  Google Scholar 

  • Direkze NC, Forbes SJ, Brittan M, Hunt T, Jeffery R, Preston SL, Poulsom R, Hodivala-Dillke K, Alison MR, Wrght NA (2003) Multiple organ engraftment by bone-marrow-derived myofibroblasts and fibroblasts in bone marrow-transplanted mice. Stem Cells 21:514–520

    Article  PubMed  Google Scholar 

  • Direkze NC, Jeffery R, Hodivala-Dilke K, Hunt T, Playford RJ, Elia G, Poulsom R, Wright NA, Alison MR (2004) Bone marrow contribution to tumor-associated myofibroblasts and fibroblasts. Cancer Res 64:8492–8495

    Article  PubMed  CAS  Google Scholar 

  • Goldblatt JP, Fitzsimmons SE, Balk E, Richmond JC (2005) Reconstruction of the anterior cruciate ligament: meta-analysis of patellar tendon versus hamstring tendon autograft. Arthroscopy 21:791–798

    PubMed  Google Scholar 

  • Jakowlew SB (2006) Transforming growth factor-b in cancer and metastasis. Cancer Metastasis Rev 25:435–457

    Article  PubMed  CAS  Google Scholar 

  • Kartus J, Movin T, Karlsson J (2001) Donor-site morbidity and anterior knee problems after anterior cruciate ligament reconstruction using autografts. Arthroscopy 17:971–980

    PubMed  CAS  Google Scholar 

  • Liechty KW, MacKenzie TC, Shaaban AF, Radu A, Moseley AM, Deans R, Marshak DR, Flake AW (2000) Human mesenchymal stem cells engraft and demonstrate site-specific differentiation after in utero transplantation in sheep. Nat Med 6:1282–1286

    Article  PubMed  CAS  Google Scholar 

  • 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 for anterior cruciate ligament reconstruction. Arthroscopy 20:899–910

    PubMed  Google Scholar 

  • Lovell MJ, Mathur A (2002) The role of stem cells for treatment of cardiovascular disease. Cell Prolif 37:67–87

    Article  Google Scholar 

  • MacKenzie TC, Flake AW (2002) Human mesenchymal stem cells: insights from a surrogate in vivo assay system. Cells Tissues Organs 171:90–95

    Article  PubMed  Google Scholar 

  • Martinek V, Latterman C, Usas A, Abramowitch S, Woo SL, Fu FH, Huard J (2002) Enhancement of tendon-bone integration of anterior cruciate ligament grafts with bone morphogenetic protein-2 gene transfer: a histological and biomechanical study. J Bone Joint Surg Am 84-A:1123–1131

    PubMed  Google Scholar 

  • Mochizuki T, Muneta T, Sakaguchi Y, Nimura A, Yokoyama A, Koga H, Sekiya I (2006) Higher chondrogenic potential of fibrous synovium- and adipose synovium-derived cells compared with subcutaneous fat-derived cells: distinguishing properties of mesenchymal stem cells in humans. Arthritis Rheum 54:843–853

    Article  PubMed  CAS  Google Scholar 

  • Mothe AJ, Tator CH (2005) Proliferation, migration, and differentiation of endogenous ependymal region stem/progenitor cells following minimal spinal cord injury in the adult rat. Neuroscience 131:177–187

    Article  PubMed  CAS  Google Scholar 

  • Ouyang HW, Goh JCH, Lee EH (2004) Use of bone marrow stromal cells for tendon graft-to-bone healing. Am J Sports Med 32:321–327

    Article  PubMed  Google Scholar 

  • Petite H, Viateau V, Bensaid W, Meunier A, de Pollak C, Bourguignon M, Oudina K, Sedel L, Guillemin G (2000) Tissue-engineered bone regeneration. Nat Biotechnol 18:959–963

    Article  PubMed  CAS  Google Scholar 

  • Ponticiello MS, Schinagl RM, Kadiyala S, Barry FP (2000) Gelatin-based resorbable sponge as a carrier matrix for human mesenchymal stem cells in cartilage regeneration therapy. J Biomed Mater Res 52:246–255

    Article  PubMed  CAS  Google Scholar 

  • Prockop DJ (1997) Marrow stromal cells as stem cells for nonhematopoietic tissues. Science 276:71–74

    Article  PubMed  CAS  Google Scholar 

  • Rodeo SA, Suzuki K, Deng XH, Wozney J, Warren RF (1999) Use of recombinant human bone morphogenetic protein-2 to enhance tendon healing in a bone tunnel. Am J Sports Med 27:476–488

    PubMed  CAS  Google Scholar 

  • Sachs RA, Daniel DM, Stone ML, Garfein RF (1989) Patellofemoral problems after anterior cruciate ligament reconstruction. Am J Sports Med 17:760–765

    Article  PubMed  CAS  Google Scholar 

  • 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 Rheum 52:2521–2529

    Article  PubMed  Google Scholar 

  • Sekiya I, Colter DC, Prockop DJ (2001) BMP-6 enhances chondrogenesis in a subpopulation of human marrow stromal cells. Biochem Biophys Res Commun 2284:411–418

    Article  CAS  Google Scholar 

  • Shi S, Gronthos S (2003) Perivascular niche of postnatal mesenchymal stem cells in human bone marrow and dental pulp. J Bone Miner Res 18:696–704

    Article  PubMed  Google Scholar 

  • Shirasawa S, Sekiya I, Sakaguchi Y, Yagishita K, Ichinose S, Muneta T (2006) In vitro chondrogenesis of human synovium-derived mesenchymal stem cells: optimal condition and comparison with bone marrow-derived cells. J Cell Biochem 97:84–97

    Article  PubMed  CAS  Google Scholar 

  • Tolar J, O’Shaughnessy MJ, Panoskaltsis-Mortari A, McElmurry RT, Bell S, Riddle M, McIvor RS, Yant SR, Kay MA, Krause D, Verfaillie CM, Blazar BR (2006) Host factors that impact the biodistribution and persistence of multipotent adult progenitor cells. Blood 107:4182–4188

    Article  PubMed  CAS  Google Scholar 

  • Tomita F, Yasuda K, Mikami S, Sakai T, Yamazaki S, Tohyama H (2001) Comparisons of intraosseous graft healing between the doubled flexor tendon graft and the bone-patellar tendon-bone graft in anterior cruciate ligament reconstruction. Arthroscopy 17:461–476

    PubMed  CAS  Google Scholar 

  • Tse WT, Pendleton JD, Beyer WM, Egalka MC, Guinan EC (2003) Suppression of allogeneic T-cell proliferation by human marrow stromal cells: implications in transplantation. Transplantation 75:389–397

    Article  PubMed  CAS  Google Scholar 

  • Yagishita K, Sekiya I, Sakaguchi Y, Shinomiya S, Muneta T (2005) The effect of hyaluronan on tendon healing in rabbits. Arthroscopy 21:1330–1336

    PubMed  Google Scholar 

  • Yamazaki S, Yasuda K, Tomita F, Tohyama H, Minami A (2005) The effect of transforming growth factor-beta 1 on intraosseous healing of flexor tendon autograft replacement of anterior cruciate ligament in dogs. Arthroscopy 21:1034–1041

    Article  PubMed  Google Scholar 

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

    Article  PubMed  CAS  Google Scholar 

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Acknowledgements

We thank Kenichi Shinomiya, MD, PhD, for continuous support and Miyoko Ojima for expert help with histology. Recombinant human BMP2 was kindly provided by Astellas Pharma.

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Authors and Affiliations

  1. Section of Orthopedic Surgery, Graduate School, Tokyo Medical and Dental University, Tokyo, Japan

    Young-Jin Ju, Takeshi Muneta, Hideya Yoshimura & Hideyuki Koga

  2. Center of Excellence Program for Frontier Research on Molecular Destruction and Reconstruction of Tooth and Bone, Tokyo Medical and Dental University, Tokyo, Japan

    Takeshi Muneta

  3. Section of Cartilage Regeneration, Graduate School, Tokyo Medical and Dental University, 1-5-45 Yushima, Bunkyo-ku, Tokyo, 113–8519, Japan

    Ichiro Sekiya

Authors
  1. Young-Jin Ju
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  2. Takeshi Muneta
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  3. Hideya Yoshimura
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  4. Hideyuki Koga
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  5. Ichiro Sekiya
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Corresponding author

Correspondence to Ichiro Sekiya.

Additional information

This study was supported in part by grants from the Japan Society for the Promotion of Science (19591752) and from the Center of Excellence Program for Frontier Research on Molecular Destruction and Reconstruction of Tooth and Bone at Tokyo Medical and Dental University to T.M. and from the Japan Society for the Promotion of Science (18591657) to I.S.

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Ju, YJ., Muneta, T., Yoshimura, H. et al. Synovial mesenchymal stem cells accelerate early remodeling of tendon-bone healing. Cell Tissue Res 332, 469–478 (2008). https://doi.org/10.1007/s00441-008-0610-z

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  • DOI: https://doi.org/10.1007/s00441-008-0610-z

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