Skip to main content

Advertisement

SpringerLink
Log in

Mesenchymal Stem Cells in the Musculoskeletal System: From Animal Models to Human Tissue Regeneration?

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

Abstract

The musculoskeletal system includes tissues that have remarkable regenerative capabilities. Bone and muscle sustain micro-damage throughout the lifetime, yet they continue to provide the body with the support that is needed for everyday activities. Our current understanding is that the regenerative capacity of the musculoskeletal system can be attributed to the mesenchymal stem/ stromal cells (MSCs) that reside within its different anatomical compartments. These MSCs can replenish various tissues with progenitor cells to form functional cells, such as osteoblasts, chondrocytes, myocytes, and others. However, with aging and in certain disorders of the musculoskeletal system such as osteoarthritis or osteoporosis, this regenerative capacity of MSCs appears to be lost or diverted for the production of other non-functional cell types, such as adipocytes and fibroblasts. In this review, we shed light on the tissue sources and subpopulations of MSCs in the musculoskeletal system that have been identified in animal models, discuss the mechanisms of their anti-inflammatory action as a prerequisite for their tissue regeneration and their current applications in regenerative medicine. While providing up-to-date evidence of the role of MSCs in different musculoskeletal pathologies, in particular in osteoporosis and osteoarthritis, we share some thoughts on their potential as diagnostic markers in musculoskeletal health and disease.

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

Access this article

Log in via an institution

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

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2

Similar content being viewed by others

References

  1. Walmsley, G. G., Ransom, R. C., Zielins, E. R., et al. (2015). Stem cells in bone regeneration. Stem Cell Reviews and Reports. https://doi.org/10.1007/s12015-016-9665-5.

    Article  Google Scholar 

  2. Tedesco, F. S., Dellavalle, A., Diaz-Manera, J., Messina, G., & Cossu, G. (2010). Repairing skeletal muscle: regenerative potential of skeletal muscle stem cells. Journal of Clinical Investigation. https://doi.org/10.1172/JCI40373.

    Article  PubMed  PubMed Central  Google Scholar 

  3. Friedenstein, A. J., Chailakhjan, R. K., & Lalykina, K. S. (1970). The development of a fibroblast colonies in monolayer cultures of guinea pig bone marrow and spleen cells. Cell Proliferation. https://doi.org/10.1111/j.1365-2184.1970.tb00347.x.

    Article  Google Scholar 

  4. Pittenger, M., Mackay, A., Beck, S., et al. (1999). Multilineage potential of adult human mesenchymal stem cells. Science. https://doi.org/10.1126/science.284.5411.143.

    Article  PubMed  Google Scholar 

  5. Hass, R., Kasper, C., Böhm, S., & Jacobs, R. (2011). Different populations and sources of human mesenchymal stem cells (MSCs): a comparison of adult and neonatal tissue-derived MSC. Cell Communication and Signaling: CCS. https://doi.org/10.1186/1478-811X-9-12.

    Article  Google Scholar 

  6. Grcevic, D., Pejda, S., Matthews, B. G., et al. (2012). In vivo fate mapping identifies mesenchymal progenitor cells. Stem Cells. https://doi.org/10.1002/stem.780.

    Article  PubMed  PubMed Central  Google Scholar 

  7. Tuli, R., Seghatoleslami, M. R., Tuli, S., et al. (2003). A simple, high-yield method for obtaining multipotential mesenchymal progenitor cells from trabecular bone. Molecular Biotechnology. https://doi.org/10.1385/MB:23:1:37.

    Article  PubMed  Google Scholar 

  8. Worthley, D. L., Churchill, M., Compton, J. T., et al. (2015). Gremlin 1 identifies a skeletal stem cell with bone, cartilage, and reticular stromal potential. Cell. https://doi.org/10.1016/j.cell.2014.11.042.

    Article  PubMed  PubMed Central  Google Scholar 

  9. Méndez-Ferrer, S., Michurina, T. V., Ferraro, F., et al. (2010). Mesenchymal and haematopoietic stem cells form a unique bone marrow niche. Nature. https://doi.org/10.1038/nature09262.

    Article  PubMed  PubMed Central  Google Scholar 

  10. Zhou, B. O., Yue, R., Murphy, M. M., Peyer, J. G., & Morrison, S. J. (2014). Leptin-receptor-expressing mesenchymal stromal cells represent the main source of bone formed by adult bone marrow. Cell Stem Cell. https://doi.org/10.1016/j.stem.2014.06.008.

    Article  PubMed  PubMed Central  Google Scholar 

  11. Chan, C. K. F., Seo, E. Y., Chen, J. Y., et al. (2015). Identification and specification of the mouse skeletal stem cell. Cell. https://doi.org/10.1016/j.cell.2014.12.002.

    Article  PubMed  PubMed Central  Google Scholar 

  12. De Bari, C., Dell’Accio, F., Tylzanowski, P., Luyten, F. P. (2001) Multipotent mesenchymal stem cells from adult human synovial membrane. Arthritis and Rheumatism, https://doi.org/10.1002/1529-0131(200108)44:8<1928::AID-ART331>3.0.CO;2-P

    Article  PubMed  Google Scholar 

  13. 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 and Rheumatism. https://doi.org/10.1002/art.21212.

    Article  PubMed  Google Scholar 

  14. Roelofs, A. J., Zupan, J., Riemen, A. H. K., et al. (2017). Joint morphogenetic cells in the adult synovium. Nature Communications. https://doi.org/10.1038/ncomms15040.

    Article  PubMed  PubMed Central  Google Scholar 

  15. Kurth, T. B., Dell’Accio, F., Crouch, V., Augello, A., Sharpe, P. T., & De Bari, C. (2011). Functional mesenchymal stem cell niches in adult mouse knee joint synovium in vivo. Arthritis and Rheumatism. https://doi.org/10.1002/art.30234.

    Article  PubMed  Google Scholar 

  16. Tan, Q., Lui, P. P., Rui, Y. F., & Wong, Y. M. (2012). Comparison of potentials of stem cells isolated from tendon and bone marrow for musculoskeletal tissue engineering. Tissue Engineering Part A. https://doi.org/10.1089/ten.TEA.2011.0362.

    Article  PubMed  Google Scholar 

  17. Lui, P. P. (2015). Markers for the identification of tendon-derived stem cells in vitro and tendon stem cells in situ – update and future development. Stem Cell Research & Therapy. https://doi.org/10.1186/s13287-015-0097-y.

    Article  Google Scholar 

  18. Sienkiewicz, D., Kulak, W., Okurowska-Zawada, B., Paszko-Patej, G., Kawnik, K (2015). Duchenne muscular dystrophy: current cell therapies. Therapeutic Advances in Neurological Disorders. https://doi.org/10.1177/1756285615586123.

    Article  PubMed  PubMed Central  Google Scholar 

  19. De Bari, C., Dell’Accio, F., Vandenabeele, F., Vermeesch, J. R., Raymackers, J. M., & Luyten, F. P. (2003). Skeletal muscle repair by adult human mesenchymal stem cells from synovial membrane. The Journal of Cell Biology. https://doi.org/10.1083/jcb.200212064.

    Article  PubMed  PubMed Central  Google Scholar 

  20. Chen, C., Qu, Z., Yin, X., et al. (2016). Efficacy of umbilical cord-derived mesenchymal stem cell-based therapy for osteonecrosis of the femoral head: a three-year follow-up study. Molecular Medicine Reports. https://doi.org/10.3892/mmr.2016.5745.

    Article  PubMed  PubMed Central  Google Scholar 

  21. Daltro, G. C., Fortuna, V., de Souza, E. S., et al. (2012). Efficacy of autologous stem cell-based therapy for osteonecrosis of the femoral head in sickle cell disease: a five-year follow-up study. Stem Cell Research & Therapy. https://doi.org/10.1186/s13287-015-0105-2.

    Article  Google Scholar 

  22. Aoyama, T., Goto, K., Kakinoki, R., et al. (2014). An exploratory clinical trial for idiopathic osteonecrosis of femoral head by cultured autologous multipotent mesenchymal stromal cells augmented with vascularized bone grafts. Tissue Engineering Part B. https://doi.org/10.1089/ten.teb.2014.0090.

    Article  Google Scholar 

  23. Rastogi, S., Sankineani, S. R., Nag, H. L., et al. (2013). Intralesional autologous mesenchymal stem cells in management of osteonecrosis of femur: a preliminary study. Musculoskeletal Surgery. https://doi.org/10.1007/s12306-013-0273-0.

    Article  PubMed  Google Scholar 

  24. Zhao, D., Cui, D., Wang, B., et al. (2012). Treatment of early stage osteonecrosis of the femoral head with autologous implantation of bone marrow-derived and cultured mesenchymal stem cells. Bone. https://doi.org/10.1016/j.bone.2011.11.002.

    Article  PubMed  PubMed Central  Google Scholar 

  25. Weel, H., Mallee, W. H., van Dijk, C. N., et al. (2015). The effect of concentrated bone marrow aspirate in operative treatment of fifth metatarsal stress fractures; a double-blind randomized controlled trial. BMC Musculoskeletal Disorders. https://doi.org/10.1186/s12891-015-0649-4.

    Article  PubMed  PubMed Central  Google Scholar 

  26. Wong, K. L., Lee, K. B., Tai, B. C., Law, P., Lee, E. H., & Hui, J. H. (2013). Injectable cultured bone marrow-derived mesenchymal stem cells in varus knees with cartilage defects undergoing high tibial osteotomy: a prospective, randomized controlled clinical trial with two years’ follow-up. Arthroscopy. https://doi.org/10.1016/j.arthro.2013.09.074.

    Article  PubMed  Google Scholar 

  27. Pers, Y.-M., Rackwitz, L., Ferreira, R., et al. (2016). Adipose mesenchymal stromal cell-based therapy for severe osteoarthritis of the knee: a phase I dose-escalation trial. Stem Cells Translational Medicine. https://doi.org/10.5966/sctm.2015-0245.

    Article  PubMed  PubMed Central  Google Scholar 

  28. Orozco, L., Munar, A., Soler, R., et al. (2013). Treatment of knee osteoarthritis with autologous mesenchymal stem cells. Transplantation. https://doi.org/10.1097/TP.0b013e318291a2da.

    Article  PubMed  Google Scholar 

  29. Freitag, J., Ford, J., Bates, D., et al. (2015). Adipose derived mesenchymal stem cell therapy in the treatment of isolated knee chondral lesions: design of a randomised controlled pilot study comparing arthroscopic microfracture versus arthroscopic microfracture combined with postoperative mesenchymal. British Medical Journal Open. https://doi.org/10.1136/bmjopen-2015-009332.

    Article  Google Scholar 

  30. Jo, C., Lee, Y., & Shin, W. (2014). Intra-articular injection of mesenchymal stem cells for the treatment of osteoarthritis of the knee: a proof-of-concept clinical trial. Stem Cells. https://doi.org/10.1002/stem.1634.

    Article  PubMed  Google Scholar 

  31. Davatchi, F., Sadeghi Abdollahi, B., Mohyeddin, M., Nikbin, B. (2016). Mesenchymal stem cell therapy for knee osteoarthritis: five years follow-up of three patients. International Journal Rheumatic Diseases. https://doi.org/10.1111/1756-185X.12670.

    Article  Google Scholar 

  32. Davatchi, F., Abdollahi, B. S., Mohyeddin, M., Shahram, F., & Nikbin, B. (2011). Mesenchymal stem cell therapy for knee osteoarthritis. Preliminary report of four patients. International Journal Rheumatic Diseases. https://doi.org/10.1111/j.1756-185X.2011.01599.x.

    Article  Google Scholar 

  33. Vega, A., Martín-Ferrero, M. A., Del Canto, F., et al. (2015). Treatment of knee osteoarthritis with allogeneic bone marrow mesenchymal stem cells. Transplantation. https://doi.org/10.1097/TP.0000000000000678.

    Article  PubMed  Google Scholar 

  34. Vangsness, C. T., Farr, J., Boyd, J., Dellaero, D. T., Mills, C. R., & LeRoux-Williams, M. (2014). Adult human mesenchymal stem cells delivered via intra-articular injection to the knee following partial medial menisectomy. The Journal of Bone and Joint Surgery. https://doi.org/10.2106/JBJS.M.00058.

    Article  PubMed  Google Scholar 

  35. Centeno, C. J., Al-Sayegh, H., Bashir, J., Goodyear, S. H., & Freeman, M. D. (2015). A prospective multi-Site registry study of a specific protocol of autologous bone marrow concentrate for the treatment of shoulder rotator cuff tears and osteoarthritis. Journal of Pain Research. https://doi.org/10.2147/JPR.S80872.

    Article  PubMed  PubMed Central  Google Scholar 

  36. Centeno, C. J., Busse, D., Kisiday, J., et al. (2008). Increased knee cartilage volume in degenerative joint disease using percutaneously implanted, autologous mesenchymal stem cells. Pain Physician, 11(3), 343–353.

    PubMed  Google Scholar 

  37. Akgun, I., Unlu, M. C., Erdal, O. A., et al. (2015). Matrix-induced autologous mesenchymal stem cell implantation versus matrix-induced autologous chondrocyte implantation in the treatment of chondral defects of the knee: a 2-year randomized study. Archives of Orthopaedic and Trauma Surgery. https://doi.org/10.1007/s00402-014-2136-z.

    Article  PubMed  Google Scholar 

  38. Koh, Y.-G., Kwon, O.-R., Kim, Y.-S., Choi, Y.-J., & Tak, D.-H. (2016). Adipose-derived mesenchymal stem cells with microfracture versus microfracture alone: two-year follow-up of a prospective randomized trial. Arthroscopy. https://doi.org/10.1016/j.arthro.2015.09.010.

    Article  PubMed  Google Scholar 

  39. Chamberlain, C. S., Saether, E. E., Aktas, E., & Vanderby, R. (2017). Mesenchymal stem cell therapy on tendon/ ligament healing. Journal of Cytokine Biology, 2(1), 112.

    Article  PubMed  PubMed Central  Google Scholar 

  40. Lee, S. Y., Kim, W., Lim, C., & Chung, S. G. (2015). Treatment of lateral epicondylosis by using allogenic adipose-derived mesenchymal stem cells: a pilot study. Stem Cells. https://doi.org/10.1002/stem.2110.

    Article  PubMed  PubMed Central  Google Scholar 

  41. Kim, S. J., Song, D. H., Park, J. W., Park, S., & Kim, S. J. (2017). Effect of bone marrow aspirate concentrate-platelet-rich plasma on tendon-derived stem cells and rotator cuff tendon tear. Cell Transplantation. https://doi.org/10.3727/096368917X694705.

    Article  PubMed  PubMed Central  Google Scholar 

  42. Alsalameh, S., Amin, R., Gemba, T., & Lotz, M. (2004). Identification of mesenchymal progenitor cells in normal and osteoarthritic human articular cartilage. Arthritis and Rheumatism. https://doi.org/10.1002/art.20269.

    Article  PubMed  Google Scholar 

  43. Pretzel, D., Linss, S., Rochler, S., et al. (2011). Relative percentage and zonal distribution of mesenchymal progenitor cells in human osteoarthritic and normal cartilage. Arthritis Research and Therapy. https://doi.org/10.1186/ar3320.

    Article  PubMed  PubMed Central  Google Scholar 

  44. Williams, R., Khan, I. M., Richardson, K., et al. (2010). Identification and clonal characterisation of a progenitor cell sub-population in normal human articular cartilage. PLoS One. https://doi.org/10.1371/journal.pone.0013246.

    Article  PubMed  PubMed Central  Google Scholar 

  45. Sacchetti, B., Funari, A., Remoli, C., et al. (2016). No identical “mesenchymal stem cells” at different times and sites: human committed progenitors of distinct origin and differentiation potential are incorporated as adventitial cells in microvessels. Stem Cell Reports. https://doi.org/10.1016/j.stemcr.2016.05.011.

    Article  PubMed  PubMed Central  Google Scholar 

  46. Al-Nbaheen, M., Vishnubalaji, R., Ali, D., et al. (2013). Human stromal (mesenchymal) stem cells from bone marrow, adipose tissue and skin exhibit differences in molecular phenotype and differentiation potential. Stem Cell Reviews and Reports. https://doi.org/10.1007/s12015-012-9365-8.

    Article  PubMed  Google Scholar 

  47. Crisan, M., Yap, S., Casteilla, L., Chen, C. W., et al. (2008). A perivascular origin for mesenchymal stem cells in multiple human organs. Cell Stem Cell. https://doi.org/10.1016/j.stem.2008.07.003.

    Article  PubMed  Google Scholar 

  48. Guimarães-Camboa, N., Cattaneo, P., Sun, Y., et al. (2017). Pericytes of multiple organs do not behave as mesenchymal stem cells in vivo. Cell Stem Cell. https://doi.org/10.1016/j.stem.2016.12.006.

    Article  PubMed  PubMed Central  Google Scholar 

  49. Murphy, J. M., Dixon, K., Beck, S., Fabian, D., Feldman, A., & Barry, F. (2002). Reduced chondrogenic and adipogenic activity of mesenchymal stem cells from patients with advanced osteoarthritis. Arthritis and Rheumatism. https://doi.org/10.1002/art.10118.

    Article  PubMed  Google Scholar 

  50. Sakaguchi, Y., Sekiya, I., Yagishita, K., Ichinose, S., Shinomiya, K., & Muneta, T. (2009). Suspended cells from trabecular bone by collagenase digestion become virtually identical to mesenchymal stem cells obtained from marrow. Stem Cells. https://doi.org/10.1182/blood-2003-12-4452.

    Article  Google Scholar 

  51. Latil, M., Rocheteau, P., Châtre, L., et al. (2012). Skeletal muscle stem cells adopt a dormant cell state post mortem and retain regenerative capacity. Nature Communications. https://doi.org/10.1038/ncomms1890.

    Article  PubMed  Google Scholar 

  52. Valente, S., Alviano, F., Ciavarella, C., et al. (2014). Human cadaver multipotent stromal/stem cells isolated from arteries stored in liquid nitrogen for 5 years. Stem Cell Research & Therapy. https://doi.org/10.1186/scrt397.

    Article  Google Scholar 

  53. Baustian, C., Hanley, S., & Ceredig, R. (2012). Isolation, selection and culture methods to enhance clonogenicity of mouse bone marrow derived mesenchymal stromal cell precursors. Stem Cell Research & Therapy. https://doi.org/10.1186/s13287-015-0139-5.

    Article  Google Scholar 

  54. Futami, I., Ishijima, M., Kaneko, H., et al. (2012). Isolation and characterization of multipotential mesenchymal cells from the mouse synovium. PLoS One. https://doi.org/10.1371/journal.pone.0045517.

    Article  PubMed  PubMed Central  Google Scholar 

  55. Zhu, H., Guo, Z.-K., Jiang, X.-X., et al. (2010). A protocol for isolation and culture of mesenchymal stem cells from mouse compact bone. Nature Protocols. https://doi.org/10.1038/nprot.2009.238.

    Article  PubMed  Google Scholar 

  56. Tsai, C.-C., Yew, T.-L., Yang, D.-C., Huang, W.-H., & Hung, S.-C. (2012) Benefits of hypoxic culture on bone marrow multipotent stromal cells. American Journal of Blood Research.

  57. Dominici, M., Le Blanc, K., Mueller, I., et al. (2006) Minimal criteria for defining multipotent mesenchymal stromal cells. The International Society for Cellular Therapy position statement. Cytotherapy. https://doi.org/10.1080/14653240600855905.

    Article  PubMed  Google Scholar 

  58. Fuchs, E., & Horsley, V. (2011). Ferreting out stem cells from their niches. Nature Cell Biology. https://doi.org/10.1038/ncb0511-513.

    Article  PubMed  PubMed Central  Google Scholar 

  59. Morikawa, S., Mabuchi, Y., Kubota, Y., et al. (2009). Prospective identification, isolation, and systemic transplantation of multipotent mesenchymal stem cells in murine bone marrow. The Journal of Experimental Medicine. https://doi.org/10.1084/jem.20091046.

    Article  PubMed  PubMed Central  Google Scholar 

  60. Pinho, S., Lacombe, J., Hanoun, M., et al. (2013). PDGFRa and CD51 mark human Nestin + sphere-forming mesenchymal stem cells capable of hematopoietic progenitor cell expansion. The Journal of Experimental Medicine. https://doi.org/10.1084/jem.20122252.

    Article  PubMed  PubMed Central  Google Scholar 

  61. Park, D., Spencer, J. A., Koh, B. I., et al. (2012). Cell stem cell endogenous bone marrow MSCs are dynamic, fate-restricted participants in bone maintenance and regeneration. Stem Cell. https://doi.org/10.1016/j.stem.2012.02.003.

    Article  PubMed  Google Scholar 

  62. Mizoguchi, T., Pinho, S., Ahmed, J., et al. (2014). Osterix marks distinct waves of primitive and definitive stromal progenitors during bone marrow development. Developmental Cell. https://doi.org/10.1016/j.devcel.2014.03.013.

    Article  PubMed  PubMed Central  Google Scholar 

  63. Liu, Y., Strecker, S., Wang, L., et al. (2013). Osterix-Cre labeled progenitor cells contribute to the formation and maintenance of the bone marrow stroma. PLoS One. https://doi.org/10.1371/journal.pone.0071318.

    Article  PubMed  PubMed Central  Google Scholar 

  64. Marecic, O., Tevlin, R., McArdle, A., et al. (2015). Identification and characterization of an injury-induced skeletal progenitor. Proceedings of the National Academy of Sciences. https://doi.org/10.1073/pnas.1513066112.

    Article  Google Scholar 

  65. Tanaka, K. K., Hall, J. K., Troy, A. A., Cornelison, D. D. W., Majka, S. M., & Olwin, B. B. (2009). Syndecan-4-expressing muscle progenitor cells in the SP engraft as satellite cells during muscle regeneration. Cell Stem Cell. https://doi.org/10.1016/j.stem.2009.01.016.

    Article  PubMed  PubMed Central  Google Scholar 

  66. Doyle, M. J., Zhou, S., Tanaka, K. K., et al. (2011). Abcg2 labels multiple cell types in skeletal muscle and participates in muscle regeneration. The Journal of Cell Biology. https://doi.org/10.1083/jcb.201103159.

    Article  PubMed  PubMed Central  Google Scholar 

  67. Meeson, A. P., Hawke, T. J., Graham, S., et al. (2004). Cellular and molecular regulation of skeletal muscle side population cells. Stem Cells. https://doi.org/10.1634/stemcells.2004-0077.

    Article  PubMed  Google Scholar 

  68. Penton, C. M., Thomas-Ahner, J. M., Johnson, E. K., McAllister, C., & Montanaro, F. (2013). Muscle side population cells from dystrophic or injured muscle adopt a fibro-adipogenic fate. PLoS One. https://doi.org/10.1371/journal.pone.0054553.

    Article  PubMed  PubMed Central  Google Scholar 

  69. Pannérec, A., Formicola, L., Besson, V., Marazzi, G., & Sassoon, D. A. (2013). Defining skeletal muscle resident progenitors and their cell fate potentials. Development. https://doi.org/10.1242/dev.089326.

    Article  PubMed  Google Scholar 

  70. Cottle, B. J., Lewis, F. C., Shone, V., & Ellison-Hughes, G. M. (2017). Skeletal muscle-derived interstitial progenitor cells (PICs) display stem cell properties, being clonogenic, self-renewing, and multi-potent in vitro and in vivo. Stem Cell Research & Therapy. https://doi.org/10.1186/s13287-017-0612-4.

    Article  Google Scholar 

  71. Mitchell, K. J., Pannerec, A., Cadot, B., et al. (2010). Identification and characterization of a non-satellite cell muscle resident progenitor during postnatal development. Nature Cell Biol. https://doi.org/10.1038/ncb2025.

    Article  PubMed  Google Scholar 

  72. Lewis, F. C., Henning, B. J., Marazzi, G., Sassoon, D., Ellison, G. M., & Nadal-Ginard, B. (2014). Porcine skeletal-muscle-derived multipotent PW1 pos /Pax7 neg interstitial cells: isolation, characterization, and long-term culture. Stem Cells Transational Medicine. https://doi.org/10.5966/sctm.2013-0174.

    Article  Google Scholar 

  73. Bosnakovski, D., Xu, Z., Li, W., et al. (2008). Prospective isolation of skeletal muscle stem cells with a Pax7 reporter. Stem Cells. https://doi.org/10.1634/stemcells.2007-1017.

    Article  PubMed  PubMed Central  Google Scholar 

  74. Seale, P., Sabourin, L. A., Girgis-Gabardo, A., Mansouri, A., Gruss, P., & Rudnicki, M. A. (2000) Pax7 is required for the specification of myogenic satellite cells skeletal muscle. Cell, 102(6), 777–786.

    Article  PubMed  CAS  Google Scholar 

  75. Xu, X., Wilschut, K. J., Kouklis, G., et al. (2015). Human satellite cell transplantation and regeneration from diverse skeletal muscles. Stem Cell Reports. https://doi.org/10.1016/j.stemcr.2015.07.016.

    Article  PubMed  PubMed Central  Google Scholar 

  76. Morosetti, R., Mirabella, M., Gliubizzi, C., et al. (2007). Isolation and characterization of mesoangioblasts from facioscapulohumeral muscular dystrophy muscle biopsies. Stem Cells. https://doi.org/10.1634/stemcells.2007-0465.

    Article  PubMed  Google Scholar 

  77. Bonfanti, C., Rossi, G., Tedesco, F. S., et al. (2015). ARTICLE PW1/Peg3 expression regulates key properties that determine mesoangioblast stem cell competence. Nature Communications. https://doi.org/10.1038/ncomms7364.

    Article  PubMed  PubMed Central  Google Scholar 

  78. Morosetti, R., Mirabella, M., Gliubizzi, C., et al. (2006). MyoD expression restores defective myogenic differentiation of human mesoangioblasts from inclusion-body myositis muscle. Proceeding of the National Academy of Sciences. https://doi.org/10.1073/pnas.0603386103.

    Article  Google Scholar 

  79. Dellavalle, A., Maroli, G., Covarello, D., et al. (2011). Pericytes resident in postnatal skeletal muscle differentiate into muscle fibres and generate satellite cells. Nature Communications. https://doi.org/10.1038/ncomms1508.

    Article  PubMed  Google Scholar 

  80. Birbrair, A., Zhang, T., Wang, Z. M., et al. (2013). Role of pericytes in skeletal muscle regeneration and fat accumulation. Stem Cells and Development. https://doi.org/10.1089/scd.2012.0647.

    Article  PubMed  PubMed Central  Google Scholar 

  81. Dellavalle, A., Sampaolesi, M., Tonlorenzi, R., et al. (2007) Pericytes of human skeletal muscle are myogenic precursors distinct from satellite cells. Nature Cell Biology, https://doi.org/10.1038/ncb1542.

    Article  PubMed  Google Scholar 

  82. Uezumi, A., Ito, T., Morikawa, D., et al. (2011). Fibrosis and adipogenesis originate from a common mesenchymal progenitor in skeletal muscle. Journal of Cell Science. https://doi.org/10.1242/jcs.086629.

    Article  PubMed  Google Scholar 

  83. Uezumi, A., Fukada, S., Yamamoto, N., Takeda, S., & Tsuchida, K. (2010). Mesenchymal progenitors distinct from satellite cells contribute to ectopic fat cell formation in skeletal muscle. Nature Cell Biology. https://doi.org/10.1038/ncb2014.

    Article  PubMed  Google Scholar 

  84. Uezumi, A., Fukada, S., Yamamoto, N., et al. (2014). Identification and characterization of PDGFRa + mesenchymal progenitors in human skeletal muscle. Cell Death & Disease. https://doi.org/10.1038/cddis.2014.161.

    Article  Google Scholar 

  85. Arrighi, N., Moratal, C., Clément, N., et al. (2015). Characterization of adipocytes derived from fibro/adipogenic progenitors resident in human skeletal muscle. Cell Death & Disease. https://doi.org/10.1038/cddis.2015.79.

    Article  Google Scholar 

  86. Joe, A. W., Yi, L., Natarajan, A., et al. (2010). Muscle injury activates resident fibro/adipogenic progenitors that facilitate myogenesis. Nature Cell Biology. https://doi.org/10.1038/ncb2015.

    Article  PubMed  PubMed Central  Google Scholar 

  87. Xu, W., Sun, Y., Zhang, J., et al. (2015). Perivascular-derived stem cells with neural crest characteristics are involved in tendon repair. Stem Cells and Development. https://doi.org/10.1089/scd.2014.0036.

    Article  PubMed  PubMed Central  Google Scholar 

  88. Runesson, E., Ackermann, P., Karlsson, J., & Eriksson, B. I. (2015). A randomised controlled trial of percutaneous fixation with kirschner wires versus volar locking-plate fixation in the treatment of adult patients with a dorsally displaced fracture of the distal radius. BMC Musculoskeletal Disorders. https://doi.org/10.1186/s12891-015-0658-3.

    Article  PubMed  PubMed Central  Google Scholar 

  89. Donahue, T., Gregersen, C., Hull, M., et al. (2015). Harnessing endogenous stem/progenitor cells for tendon regeneration. Journal of Biomechanical Engineering. https://doi.org/10.1172/JCI81589.

    Article  Google Scholar 

  90. Dyment, N. A., Hagiwara, Y., Matthews, B. G., Li, Y., Kalajzic, I., & Rowe, D. W. (2014). Lineage tracing of resident tendon progenitor cells during growth and natural healing. PLoS One. https://doi.org/10.1371/journal.pone.0096113.

    Article  PubMed  PubMed Central  Google Scholar 

  91. Fukada, S., Higuchi, S., Segawa, M., et al. (2004). Purification and cell-surface marker characterization of quiescent satellite cells from murine skeletal muscle by a novel monoclonal antibody. Experimental Cell Research. https://doi.org/10.1016/j.yexcr.2004.02.018.

    Article  PubMed  Google Scholar 

  92. Kuyinu, E. L., Narayanan, G., Nair, L. S., & Laurencin, C. T. (2016). Animal models of osteoarthritis: classification, update, and measurement of outcomes. Journal of Orthopaedic Surgery and Research. https://doi.org/10.1186/s13018-016-0346-5.

    Article  PubMed  PubMed Central  Google Scholar 

  93. Mills, L. A., & Simpson, A. H. (2012). In vivo models of bone repair. Bone Joint and Journal. https://doi.org/10.1302/0301-620X.94B7.27370.

    Article  Google Scholar 

  94. Hardy, D., Besnard, A., Latil, M., et al. (2016). Comparative study of injury models for studying muscle regeneration in mice. PLoS One. https://doi.org/10.1371/journal.pone.0147198.

    Article  PubMed  PubMed Central  Google Scholar 

  95. Carpenter, J. E., & Hankenson, K. D. (2004). Animal models of tendon and ligament injuries for tissue engineering applications. Biomaterials. https://doi.org/10.1016/S0142-9612(03)00507-6.

    Article  PubMed  Google Scholar 

  96. Docheva, D., Müller, S. A., Majewski, M., & Evans, C. H. (2015). Biologics for tendon repair. Advanced Drug Delivery Reviews. https://doi.org/10.1016/j.addr.2014.11.015.

    Article  PubMed  Google Scholar 

  97. Hast, M. W., Zuskov, A., & Soslowsky, L. J. (2014). The role of animal models in tendon research. Bone and Joint Research. https://doi.org/10.1302/2046-3758.36.2000281.

    Article  PubMed  PubMed Central  Google Scholar 

  98. Kfoury, Y., & Scadden, D. T. (2015). Cell stem cell mesenchymal cell contributions to the stem cell niche. Stem Cells. https://doi.org/10.1016/j.stem.2015.02.019.

    Article  Google Scholar 

  99. Omatsu, Y., Seike, M., Sugiyama, T., Kume, T., & Nagasawa, T. (2014). Foxc1 is a critical regulator of haematopoietic stem/ progenitor cell niche formation. Nature. https://doi.org/10.1038/nature13071.

    Article  PubMed  Google Scholar 

  100. Isern, J., Martín-Antonio, B., Ghazanfari, R., et al. (2013). Self-renewing human bone marrow mesenspheres promote hematopoietic stem cell expansion. Cell Reports. https://doi.org/10.1016/j.celrep.2013.03.041.

    Article  PubMed  Google Scholar 

  101. Ding, L., Saunders, T. L., Enikolopov, G., & Morrison, S. J. (2012). Endothelial and perivascular cells maintain haematopoietic stem cells. Nature. https://doi.org/10.1038/nature10783.

    Article  PubMed  PubMed Central  Google Scholar 

  102. Kunisaki, Y., Bruns, I., Scheiermann, C., et al. (2013). Arteriolar niches maintain haematopoietic stem cell quiescence. Nature. https://doi.org/10.1038/nature12612.

    Article  PubMed  PubMed Central  Google Scholar 

  103. Fernandez-Moure, J. S., Corradetti, B., Chan, P., et al. (2015). Enhanced osteogenic potential of mesenchymal stem cells from cortical bone: a comparative analysis. Stem Cell Research & Therapy. https://doi.org/10.1186/s13287-015-0193-z.

    Article  Google Scholar 

  104. Li, H., Ghazanfari, R., Zacharaki, D., et al. (2014). Low/ negative expression of PDGFR-α identifies the candidate primary mesenchymal stromal cells in adult human bone marrow. Stem Cell Reports. https://doi.org/10.1016/j.stemcr.2014.09.018.

    Article  PubMed  PubMed Central  Google Scholar 

  105. Campbell, T. M., Churchman, S. M., Gomez, A., et al. (2016). Mesenchymal stem cell alterations in bone marrow lesions in patients with hip osteoarthritis. Arthritis & Rheumatology. https://doi.org/10.1002/art.39622.

    Article  Google Scholar 

  106. Lee, W. C., Shi, H., Poon, Z., et al. (2014). Multivariate biophysical markers predictive of mesenchymal stromal cell multipotency. Proceedings of the National Academy of Science. https://doi.org/10.1073/pnas.1402306111.

    Article  Google Scholar 

  107. Johnson, K., Zhu, S., Tremblay, M. S., et al. (2013). A stem-cell–based approach to cartilage repair. Science. https://doi.org/10.1126/science.1229223.

    Article  PubMed  PubMed Central  Google Scholar 

  108. Mauro, A. (1961). Satellite cell of skeletal muscle fibers. The Journal of Biophysical and Biochemical Cytology. https://doi.org/10.1083/jcb.9.2.493.

    Article  PubMed  PubMed Central  Google Scholar 

  109. Muir, A. R., Kanji, A. H., & Allbrook, D. (1965). The structure of the satellite cells in skeletal muscle. Journal of Anatomy, 99(Pt 3), 435–444.

    PubMed  PubMed Central  CAS  Google Scholar 

  110. Goodell, M. A., Brose, K., Paradis, G., Conner, A. S., & Mulligan, R. C. (1996). Isolation and functional properties of murine hematopoietic stem cells that are replicating in vivo. The Journal of Experimental Medicine. https://doi.org/10.1084/jem.183.4.1797.

    Article  PubMed  Google Scholar 

  111. Montanaro, F., Liadaki, K., Schienda, J., Flint, A., Gussoni, E., & Kunkel, L. M. (2004). Demystifying SP cell purification: Viability, yield, and phenotype are defined by isolation parameters. Experimental Cell Research. https://doi.org/10.1016/j.yexcr.2004.04.010.

    Article  PubMed  Google Scholar 

  112. Uezumi, A., Ojima, K., Fukada, S., et al. (2006). Functional heterogeneity of side population cells in skeletal muscle. Biochemical and Biophysical Research Communications. https://doi.org/10.1016/j.bbrc.2006.01.037.

    Article  PubMed  Google Scholar 

  113. Zhou, S., Schuetz, J. D., Bunting, K. D., et al. (2001). The ABC transporter Bcrp1/ABCG2 is expressed in a wide variety of stem cells and is a molecular determinant of the side-population phenotype. Nature Medicine. https://doi.org/10.1038/nm0901-1028.

    Article  PubMed  Google Scholar 

  114. Asakura, A., Seale, P., Girgis-Gabardo, A., & Rudnicki, M. A. (2002). Myogenic specification of side population cells in skeletal muscle. The Journal of Cell Biology. https://doi.org/10.1083/jcb.200202092.

    Article  PubMed  PubMed Central  Google Scholar 

  115. Sampaolesi, M., Torrente, Y., Innocenzi, A., et al. (2003). Cell therapy of α-sarcoglycan-null dystrophic mice through intra-arterial delivery of mesoangioblasts. Science. https://doi.org/10.1126/science.1082254.

    Article  PubMed  Google Scholar 

  116. Galvez, B. G., Sampaolesi, M., Brunelli, S., et al. (2006). Complete repair of dystrophic skeletal muscle by mesoangioblasts with enhanced migration ability. The Journal of Cell Biology. https://doi.org/10.1083/jcb.200512085.

    Article  PubMed  PubMed Central  Google Scholar 

  117. Sampaolesi, M., Blot, S., D’Antona, G., et al. (2006). Mesoangioblast stem cells ameliorate muscle function in dystrophic dogs. Nature. https://doi.org/10.1038/nature05282.

    Article  PubMed  Google Scholar 

  118. Cossu, G., Previtali, S. C., Napolitano, S., et al. (2015). Intra-arterial transplantation of HLA-matched donor mesoangioblasts in Duchenne muscular dystrophy. EMBO Molecular Medicine. https://doi.org/10.15252/emmm.201505636.

    Article  PubMed  PubMed Central  Google Scholar 

  119. Relaix, F., & Zammit, P. S. (2012). Satellite cells are essential for skeletal muscle regeneration: the cell on the edge returns centre stage. Development. https://doi.org/10.1242/dev.069088.

    Article  PubMed Central  PubMed  Google Scholar 

  120. Sambasivan, R., Yao, R., Kissenpfennig, A., Van Wittenberghe, L., et al. (2011). Pax7-expressing satellite cells are indispensable for adult skeletal muscle regeneration. Development. https://doi.org/10.1242/dev.067587.

    Article  PubMed  Google Scholar 

  121. Hernandez-Torres, F., Rodríguez-Outeiriño, L., Franco, D., & Aranega, A. E. (2017). Pitx2 in embryonic and adult myogenesis. Frontiers in Cell and Development Biology. https://doi.org/10.3389/fcell.2017.00046.

    Article  Google Scholar 

  122. Zhang, J., & Wang, J. (2013). Human tendon stem cells better maintain their stemness in hypoxic culture conditions. PLoS One. https://doi.org/10.1371/journal.pone.0061424.

    Article  PubMed  PubMed Central  Google Scholar 

  123. 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. https://doi.org/10.1038/nm1630.

    Article  PubMed  Google Scholar 

  124. Po, P., & Lui, Y. (2015). Stem cell technology for tendon regeneration: current status, challenges, and future research directions. Stem Cells Cloning: Advances and Applications. https://doi.org/10.2147/SCCAA.S60832.

    Article  Google Scholar 

  125. Zhang, X., Lin, Y. C., Rui, Y. F., et al. (2016). Therapeutic roles of tendon stem/ progenitor cells in tendinopathy. Stem Cells International. https://doi.org/10.1155/2016/4076578.

    Article  PubMed  PubMed Central  Google Scholar 

  126. Lee, K. J., Clegg, P. D., Comerford, E. J., & Canty-Laird, E. G. (2017). Ligament-derived stem cells: identification, characterisation, and therapeutic application. Stem Cells International. https://doi.org/10.1155/2017/1919845.

    Article  PubMed  PubMed Central  Google Scholar 

  127. Cheng, M. T., Yang, H. W., Chen, T. H., & Lee, O. K. (2009). Isolation and characterization of multipotent stem cells from human cruciate ligaments. Cell Proliferation. https://doi.org/10.1111/j.1365-2184.2009.00611.x.

    Article  PubMed  Google Scholar 

  128. de Sousa, E., Casado, P., Neto, V., Duarte, M. E., & Aguiar, D. (2014). Synovial fluid and synovial membrane mesenchymal stem cells: latest discoveries and therapeutic perspectives. Stem Cell Research & Therapy. https://doi.org/10.1186/scrt501.

    Article  Google Scholar 

  129. Spees, J. L., Lee, R. H., & Gregory, C. A. (2016). Mechanisms of mesenchymal stem/stromal cell function. Stem Cell Research & Therapy. https://doi.org/10.1186/s13287-016-0363-7.

    Article  Google Scholar 

  130. Zachar, L., Bačenková, D., & Rosocha, J. (2016). Activation, homing, and role of the mesenchymal stem cells in the inflammatory environment. Journal of Inflammation Research. https://doi.org/10.2147/JIR.S121994.

    Article  PubMed  PubMed Central  Google Scholar 

  131. Schepers, K., & Fibbe, W. E. (2016). Unraveling mechanisms of mesenchymal stromal cell-mediated immunomodulation through patient monitoring and product characterization. Annals of the New York Academy of Sciences. https://doi.org/10.1111/nyas.12984.

    Article  PubMed  Google Scholar 

  132. Zhao, Q., Ren, H., & Han, Z. (2016). Mesenchymal stem cells: Immunomodulatory capability and clinical potential in immune diseases. Journal of Cellular Immunotherapy. https://doi.org/10.1016/j.jocit.2014.12.001.

    Article  Google Scholar 

  133. Regulski, M. J. (2017). Mesenchymal stem cells: “guardians of inflammation.” Wounds, 29, 20–27.

    PubMed  Google Scholar 

  134. Nishizawa, K., & Seki, R. (2016). Mechanisms of immunosuppression by mesenchymal stromal cells: a review with a focus on molecules. Biomedical Research and Clinical Practice. https://doi.org/10.15761/BRCP.1000116.

    Article  Google Scholar 

  135. Glenn, J. D. (2014). Mesenchymal stem cells: emerging mechanisms of immunomodulation and therapy. World Journal of Stem Cells. https://doi.org/10.4252/wjsc.v6.i5.526.

    Article  PubMed  PubMed Central  Google Scholar 

  136. Gruh, I., & Martin, U. (2009). Transdifferentiation of stem cells: a critical view. Engineering of Stem Cells. https://doi.org/10.1007/10_2008_49.

    Article  Google Scholar 

  137. Prockop, D. J., & Oh, J. Y. (2012). Medical therapies with adult stem/progenitor cells (MSCs): a backward journey from dramatic results in vivo to the cellular and molecular explanations. Journal of Cellular Biochemistry. https://doi.org/10.1002/jcb.24046.

    Article  PubMed  PubMed Central  Google Scholar 

  138. Sottile, F., Aulicino, F., Theka, I., & Cosma, M. P. (2016). Mesenchymal stem cells generate distinct functional hybrids in vitro via cell fusion or entosis. Scientific Reports. https://doi.org/10.1038/srep36863.

    Article  PubMed  PubMed Central  Google Scholar 

  139. Usunier, B., Benderitter, M., Tamarat, R., & Chapel, A. (2014). Management of fibrosis: the mesenchymal stromal cells breakthrough. Stem Cells International. https://doi.org/10.1155/2014/340257.

    Article  PubMed  PubMed Central  Google Scholar 

  140. Islam, M. N., Das, S. R., Emin, M. T., et al. (2012). Mitochondrial transfer from bone marrow-derived stromal cells to pulmonary alveoli protects against acute lung injury. Nature Medicine. https://doi.org/10.1038/nm.2736.

    Article  PubMed  PubMed Central  Google Scholar 

  141. Chinnery, H. R., Pearlman, E., & McMenamin, P. G. (2008). Cutting edge: Membrane nanotubes in vivo: a feature of MHC class II + cells in the mouse cornea. Journal of Immunology, 180(9), 5779–5783.

    Article  CAS  Google Scholar 

  142. Liu, K., Ji, K., Guo, L., et al. (2014). Mesenchymal stem cells rescue injured endothelial cells in an in vitro ischemia–reperfusion model via tunneling nanotube like structure-mediated mitochondrial transfer. Microvascular Research. https://doi.org/10.1016/j.mvr.2014.01.008.

    Article  PubMed  PubMed Central  Google Scholar 

  143. Valadi, H., Ekström, K., Bossios, A., Sjöstrand, M., Lee, J. J., & Lötvall, J. O. (2007). Exosome-mediated transfer of mRNAs and microRNAs is a novel mechanism of genetic exchange between cells. Nature Cell Biology. https://doi.org/10.1038/ncb1596.

    Article  PubMed  Google Scholar 

  144. Viganò, M., Sansone, V., d’Agostino, M. C., Romeo, P., Perucca Orfei, C., & de Girolamo, L. (2016). Mesenchymal stem cells as therapeutic target of biophysical stimulation for the treatment of musculoskeletal disorders. Journal of Orthopaedic Surgery and Research. https://doi.org/10.1186/s13018-016-0496-5.

    Article  PubMed  PubMed Central  Google Scholar 

  145. Coelho, M. B., Cabral, J. M. S., & Karp, J. M. (2012). Intraoperative stem cell therapy. Annual Review of Biomedical Engineering. https://doi.org/10.1146/annurev-bioeng-071811-150041.

    Article  PubMed  PubMed Central  Google Scholar 

  146. Veronesi, F., Giavaresi, G., Tschon, M., Borsari, V., Nicoli Aldini, N., & Fini, M. (2013). Clinical use of bone marrow, bone marrow concentrate, and expanded bone marrow mesenchymal stem cells in cartilage disease. Stem Cells and Development. https://doi.org/10.1089/scd.2012.0373.

    Article  PubMed  Google Scholar 

  147. Hernigou, P., Homma, Y., Flouzat Lachaniette, C.H., et al (2013). Benefits of small volume and small syringe for bone marrow aspirations of mesenchymal stem cells. International Orthopaedics. https://doi.org/10.1007/s00264-013-2017-z.

  148. Otsuru, S., Hofmann, T. J., Olson, T. S., Dominici, M., & Horwitz, E. M. (2013). Improved isolation and expansion of bone marrow mesenchymal stromal cells using a novel marrow filter device. Cytotherapy. https://doi.org/10.1016/j.jcyt.2012.10.012.

    Article  PubMed  Google Scholar 

  149. Ito, K., Aoyama, T., Fukiage, K., et al. (2010). A novel method to isolate mesenchymal stem cells from bone marrow in a closed system using a device made by nonwoven fabric. Tissue Engineering Part C Methods. https://doi.org/10.1089/ten.TEC.2008.0693.

    Article  PubMed  Google Scholar 

  150. Zuk, P. A., Zhu, M., Mizuno, H., et al. (2001). Multilineage cells from human adipose tissue: implications for cell-based therapies. Tissue Engineering. https://doi.org/10.1089/107632701300062859.

    Article  PubMed  Google Scholar 

  151. Lendeckel, S., Jödicke, A., Christophis, P., et al. (2004). Autologous stem cells (adipose) and fibrin glue used to treat widespread traumatic calvarial defects: case report. Journal of Cranio-Maxillofacial Surgery. https://doi.org/10.1016/j.jcms.2004.06.002.

    Article  PubMed  Google Scholar 

  152. Baer, P. C., & Geiger, H. (2012). Adipose-derived mesenchymal stromal/stem cells: tissue localization, characterization, and heterogeneity. Stem Cells International. https://doi.org/10.1155/2012/812693.

    Article  PubMed  PubMed Central  Google Scholar 

  153. Fraser, J. K., Zhu, M., Wulur, I., & Alfonso, Z. (2008). Adipose-derived stem cells. Methods in Molecular Biology. https://doi.org/10.1007/978-1-60327-169-1_4.

    Article  PubMed  Google Scholar 

  154. Pak, J., Lee, J. H., Park, K. S., Park, M., Kang, L. W., & Lee, S. H. (2017). Current use of autologous adipose tissue-derived stromal vascular fraction cells for orthopedic applications. Journal of Biomedical Sciences. https://doi.org/10.1186/s12929-017-0318-z.

    Article  Google Scholar 

  155. Ancans, J. (2012). Cell therapy medicinal product regulatory framework in Europe and its application for MSC-based therapy development. Frontiers in Immunology. https://doi.org/10.3389/fimmu.2012.00253.

    Article  PubMed  PubMed Central  Google Scholar 

  156. Kristjánsson, B., & Honsawek, S. (2014). Current perspectives in mesenchymal stem cell therapies for osteoarthritis. Stem Cells International. https://doi.org/10.1155/2014/194318.

    Article  PubMed  PubMed Central  Google Scholar 

  157. Reissis, D., Tang, Q. O., Cooper, N. C., et al. (2016). Current clinical evidence for the use of mesenchymal stem cells in articular cartilage repair. Expert Opinion on Biological Therapy. https://doi.org/10.1517/14712598.2016.1145651.

    Article  PubMed  Google Scholar 

  158. Centeno, C. J., Al-Sayegh, H., Freeman, M. D., Smith, J., Murrell, W. D., & Bubnov, R. (2016). A multi-center analysis of adverse events among two thousand, three hundred and seventy two adult patients undergoing adult autologous stem cell therapy for orthopaedic conditions. International Orthopaedics. https://doi.org/10.1007/s00264-016-3162-y.

    Article  PubMed  Google Scholar 

  159. Deng, Z., Jin, J., Zhao, J., & Xu, H. (2016). Cartilage defect treatments: With or without cells? Mesenchymal stem cells or chondrocytes? Traditional or matrix-assisted? A systematic review and meta-analyses. Stem Cells International. https://doi.org/10.1155/2016/9201492.

    Article  PubMed  PubMed Central  Google Scholar 

  160. Kon, E., Roffi, A., Filardo, G., Tesei, G., & Marcacci, M. (2015). Scaffold-based cartilage treatments: with or without cells? A systematic review of preclinical and clinical evidence. Arthroscopy. https://doi.org/10.1016/j.arthro.2014.11.017.

    Article  PubMed  Google Scholar 

  161. Merlos-Suárez, A., Barriga, F. M., Jung, P., et al. (2011). The intestinal stem cell signature identifies colorectal cancer stem cells and predicts disease relapse. Cell Stem Cell. https://doi.org/10.1016/j.stem.2011.02.020.

    Article  PubMed  Google Scholar 

  162. Cao, C., Dong, Y., & Dong, Y. (2005). [Study on culture and in vitro osteogenesis of blood-derived human mesenchymal stem cells]. Zhongguo Xiu Fu Chong Jian Wai Ke Za Zhi, 19, 642–647.

    PubMed  CAS  Google Scholar 

  163. Kassis, I., Zangi, L., Rivkin, R., et al. (2006). Isolation of mesenchymal stem cells from G-CSF-mobilized human peripheral blood using fibrin microbeads. Bone Marrow Transplant. https://doi.org/10.1038/sj.bmt.1705358.

    Article  PubMed  Google Scholar 

  164. Pino, A. M., Rosen, C. J., & Rodríguez, J. P. (2012). In Osteoporosis, differentiation of mesenchymal stem cells (MSCs) improves bone marrow adipogenesis. Biological Research. https://doi.org/10.4067/S0716-97602012000300009.

    Article  PubMed  Google Scholar 

  165. Rodríguez, J. P., Garat, S., Gajardo, H., Pino, A. M., & Seitz, G. (1999). Abnormal osteogenesis in osteoporotic patients is reflected by altered mesenchymal stem cells dynamics. Journal of Cellular Biochemistry. https://doi.org/10.1002/(SICI)1097-4644(19991201)75:3<414::AID-JCB7>3.0.CO;2-C

    Article  PubMed  Google Scholar 

  166. Rosen, C. J., & Bouxsein, M. L. (2006). Mechanisms of disease: is osteoporosis the obesity of bone? Nature Clinical Practice Rheumatology. https://doi.org/10.1038/ncprheum0070.

    Article  PubMed  Google Scholar 

  167. D’Ippolito, G., Schiller, P. C., Ricordi, C., Roos, B. A., & Howard, G. A. (1999). Age-related osteogenic potential of mesenchymal stromal stem cells from human vertebral bone marrow. Journal of Bone and Mineral Research. https://doi.org/10.1359/jbmr.1999.14.7.1115.

    Article  PubMed  Google Scholar 

  168. Gunawardene, P., Bermeo, S., Vidal, C., et al. (2016). Association between circulating osteogenic progenitor cells and disability and frailty in older persons: the Nepean osteoporosis and frailty study. The Journals of Gerontology Series A, Biological Sciences and Medical Sciences. https://doi.org/10.1093/gerona/glv190.

    Article  PubMed  Google Scholar 

  169. Yu, B., & Wang, C. Y. (2016). Osteoporosis: the result of an “aged” bone microenvironment. Trends Mol Med. https://doi.org/10.1016/j.molmed.2016.06.002.

    Article  PubMed  PubMed Central  Google Scholar 

  170. Benisch, P., Schilling, T., Klein-Hitpass, L., et al. (2012). The transcriptional profile of mesenchymal stem cell populations in primary osteoporosis is distinct and shows overexpression of osteogenic inhibitors. PLoS One. https://doi.org/10.1371/journal.pone.0045142.

    Article  PubMed  PubMed Central  Google Scholar 

  171. Marco, F., Milena, F., Gianluca, G., & Vittoria, O. (2005). Peri-implant osteogenesis in health and osteoporosis. Micron. https://doi.org/10.1016/j.micron.2005.07.008.

    Article  PubMed  Google Scholar 

  172. Heilmeier, U., Hackl, M., Skalicky, S., et al. (2016). Serum miRNA signatures are indicative of skeletal fractures in postmenopausal women with and without type 2 diabetes and influence of osteogenic and adipogenic differentiation of adipose-tissue-derived mesenchymal stem cells in vitro. Journal of Bone and Mineral Research. https://doi.org/10.1002/jbmr.2897.

    Article  PubMed  Google Scholar 

  173. Barry, F., & Murphy, M. (2013). Mesenchymal stem cells in joint disease and repair. Nature Reviews Rheumatology. https://doi.org/10.1038/nrrheum.2013.109.

    Article  PubMed  Google Scholar 

  174. Hermida-Gómez, T., Fuentes-Boquete, I., Gimeno-Longas, M. J., et al. (2011). Quantification of cells expressing mesenchymal stem cell markers in healthy and osteoarthritic synovial membranes. The Journal of Rheumatology. https://doi.org/10.3899/jrheum.100614.

    Article  PubMed  Google Scholar 

  175. Findlay, D. M., & Kuliwaba, J. S. (2016). Bone–cartilage crosstalk: a conversation for understanding osteoarthritis. Bone Research. https://doi.org/10.1038/boneres.2016.28.

    Article  PubMed  PubMed Central  Google Scholar 

  176. Kalinkovich, A., & Livshits, G. (2015). Sarcopenia–The search for emerging biomarkers. Ageing Research Reviews. https://doi.org/10.1016/j.arr.2015.05.001.

    Article  PubMed  Google Scholar 

  177. Sousa-Victor, P., & Muñoz-Cánoves, P. (2016). Regenerative decline of stem cells in sarcopenia. Molecular Aspects of Medicine. https://doi.org/10.1016/j.mam.2016.02.002.

    Article  PubMed  Google Scholar 

  178. Sousa-Victor, P., Gutarra, S., García-Prat, L., et al. (2014). Geriatric muscle stem cells switch reversible quiescence into senescence. Nature. https://doi.org/10.1038/nature13013.

    Article  PubMed  Google Scholar 

  179. Fry, C. S., Lee, J. D., Mula, J., et al. (2015). Inducible depletion of satellite cells in adult, sedentary mice impairs muscle regenerative capacity without affecting sarcopenia. Nature Medicine. https://doi.org/10.1038/nm.3710.

    Article  PubMed Central  PubMed  Google Scholar 

  180. Dennison, E. M., Sayer, A. A., & Cooper, C. (2017). Epidemiology of sarcopenia and insight into possible therapeutic targets. Nature Reviews Rheumatology. https://doi.org/10.1038/nrrheum.2017.60.

    Article  PubMed  Google Scholar 

  181. Snijders, T., Verdijk, L. B., & van Loon, L. J. C. (2009). The impact of sarcopenia and exercise training on skeletal muscle satellite cells. Ageing Research Reviews. https://doi.org/10.1016/j.arr.2009.05.003.

    Article  PubMed  Google Scholar 

  182. Emery, A. E. H. (1991). Population frequencies of inherited neuromuscular diseases-A world survey. Neuromuscular Disorders. https://doi.org/10.1016/0960-8966(91)90039-U.

    Article  PubMed  Google Scholar 

  183. Song, Y., Yao, S., Liu, Y., et al. (2017). Expression levels of TGF-β1 and CTGF are associated with the severity of Duchenne muscular dystrophy. Experimental and Therapeutic Medicine. https://doi.org/10.3892/etm.2017.4105.

    Article  PubMed  PubMed Central  Google Scholar 

  184. Almeida, C. F., Martins, P. C., & Vainzof, M. (2016). Comparative transcriptome analysis of muscular dystrophy models Largemyd, Dmdmdx/Largemyd and Dmdmdx: what makes them different? European Journal of Human Genetics. https://doi.org/10.1038/ejhg.2016.16.

    Article  PubMed  PubMed Central  Google Scholar 

  185. Dumont, N. A., Xin Wang, Y., & von Maltzahn, J. (2015). Dystrophin expression in muscle stem cells regulates their polarity and asymmetric division. Nature Medicine. https://doi.org/10.1038/nm.3990.

    Article  PubMed  PubMed Central  Google Scholar 

  186. Marg, A., Escobar, H., Gloy, S., et al. (2014). Human satellite cells have regenerative capacity and are genetically manipulable. Journal of Clinical Investigation. https://doi.org/10.1172/JCI63992.

    Article  PubMed  PubMed Central  Google Scholar 

  187. Wang, Y., Han, Z., Song, Y., & Han, Z. C. (2012). Safety of mesenchymal stem cells for clinical application. Stem Cells International. https://doi.org/10.1155/2012/652034.

    Article  PubMed  PubMed Central  Google Scholar 

  188. Lu, X., & Zhao, T. (2013). Clinical Therapy using iPSCs: Hopes and Challenges. Genomics, Proteomics & Bioinformatics. https://doi.org/10.1016/j.gpb.2013.09.002.

    Article  PubMed Central  Google Scholar 

  189. Liu, X., Li, W., Fu, X., & Xu, Y. (2017). The immunogenicity and immune tolerance of pluripotent stem cell derivatives. Frontiers in Immunology. https://doi.org/10.3389/fimmu.2017.00645.

    Article  PubMed  PubMed Central  Google Scholar 

Download references

Acknowledgements

The authors acknowledge Chris Berrie for scientific English editing of the manuscript. J. Zupan was funded by UK Arthritis Research as a Postdoctoral Research Fellow at the University of Aberdeen (2014–2016) and by P3-0298 research program of Slovenian Research Agency (2009–2014 and since 2016) as Researcher at the University of Ljubljana. Figures were created using the Mind the Graph platform (http://www.mindthegraph.com).

Author information

Authors and Affiliations

  1. Faculty of Pharmacy, University of Ljubljana, Askerceva 7, 1000, Ljubljana, Slovenia

    Klemen Čamernik, Janja Marc, Matjaž Jeras & Janja Zupan

  2. EDUCELL Cell Therapy Service, Prevale 9, 1236, Trzin, Slovenia

    Ariana Barlič

  3. Department of Orthopaedic Surgery, University Medical Centre Ljubljana, Zaloska cesta 9, 1000, Ljubljana, Slovenia

    Matej Drobnič

Authors
  1. Klemen Čamernik
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Ariana Barlič
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Matej Drobnič
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Janja Marc
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Matjaž Jeras
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Janja Zupan
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding authors

Correspondence to Matjaž Jeras or Janja Zupan.

Ethics declarations

Conflict of Interest

The authors declare that they have no conflict of interest.

Additional information

Matjaž Jeras and Janja Zupan are co-seniors.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Čamernik, K., Barlič, A., Drobnič, M. et al. Mesenchymal Stem Cells in the Musculoskeletal System: From Animal Models to Human Tissue Regeneration?. Stem Cell Rev and Rep 14, 346–369 (2018). https://doi.org/10.1007/s12015-018-9800-6

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s12015-018-9800-6

Keywords

Search

Navigation