Cyclic tensile strain enhances human mesenchymal stem cell Smad 2/3 activation and tenogenic differentiation in anisotropic collagen-glycosaminoglycan scaffolds

Eur Cell Mater. 2017 Mar 20;33:227-239. doi: 10.22203/eCM.v033a14.


Stem cell research arose from the need to explore new therapeutic possibilities for intractable and lethal diseases. Although musculoskeletal disorders are basically nonlethal, their high prevalence and relative ease of performing clinical trials have facilitated the clinical application of stem cells in this field. However, few reliable clinical studies have been published, despite the plethora of in vitro and preclinical studies in stem cell research for regenerative medicine in the musculoskeletal system. Stem cell therapy can be applied locally for bone, cartilage and tendon regeneration. Candidate disease modalities in bone regeneration include large bone defects, nonunion of fractures, and osteonecrosis. Focal osteochondral defect and osteoarthritis are current targets for cartilage regeneration. For tendon regeneration, bone-tendon junction problems such as rotator cuff tears are hot topics in clinical research. To date, the literature supporting stem cell-based therapies comprises mostly case reports or case series. Therefore, high-quality evidence, including from randomised clinical trials, is necessary to define the role of cell-based therapies in the treatment of musculoskeletal disorders. It is imperative that clinicians who adopt stem cell treatment into their practices possess a good understanding of the natural course of the disease. It is also highly recommended that treating physicians do not thrust aside the concomitant use of established measures until stem cell therapy is evidently proved worthy in terms of efficacy and cost. The purpose of this review is to summarise on the current status of stem cell application in the orthopaedic field along with the author's view of future prospects.

MeSH terms

  • Animals
  • Anisotropy
  • Bioreactors
  • Cattle
  • Cell Differentiation* / drug effects
  • Cell Proliferation / drug effects
  • Cell Survival / drug effects
  • Collagen / pharmacology*
  • Extracellular Matrix / drug effects
  • Extracellular Matrix / metabolism
  • Gene Expression Regulation / drug effects
  • Glycosaminoglycans / pharmacology*
  • Humans
  • Mechanotransduction, Cellular / drug effects
  • Mesenchymal Stem Cells / cytology*
  • Mesenchymal Stem Cells / drug effects
  • Mesenchymal Stem Cells / metabolism
  • Signal Transduction / drug effects
  • Smad Proteins / metabolism*
  • Stress, Mechanical*
  • Tendons / cytology*
  • Tensile Strength
  • Tissue Scaffolds / chemistry*


  • Glycosaminoglycans
  • Smad Proteins
  • Collagen