title: Mesenchymal stem cells as therapeutic target of biophysical stimulation for the treatment of musculoskeletal disorders.
abstract: BACKGROUND
  Musculoskeletal disorders are regarded as a major cause of worldwide morbidity and disability, and they result in huge costs for national health care systems. Traditional therapies frequently turned out to be poorly effective in treating bone, cartilage, and tendon disorders or joint degeneration. As a consequence, the development of novel biological therapies that can treat more effectively these conditions should be the highest priority in regenerative medicine. Mesenchymal stem cells (MSCs) represent one of the most promising tools in musculoskeletal tissue regenerative medicine, thanks to their proliferation and differentiation potential and their immunomodulatory and trophic ability. Indeed, MSC-based approaches have been proposed for the treatment of almost all orthopedic conditions, starting from different cell sources, alone or in combination with scaffolds and growth factors, and in one-step or two-step procedures. While all these approaches would require cell harvesting and transplantation, the possibility to stimulate the endogenous MSCs to enhance their tissue homeostasis activity represents a less-invasive and cost-effective therapeutic strategy. Nowadays, the role of tissue-specific resident stem cells as possible therapeutic target in degenerative pathologies is underinvestigated. Biophysical stimulations, and in particular extracorporeal shock waves treatment and pulsed electromagnetic fields, are able to induce proliferation and support differentiation of MSCs from different origins and affect their paracrine production of growth factors and cytokines.
  
  
  CONCLUSIONS
  The present review reports the attempts to exploit the resident stem cell potential in musculoskeletal pathologies, highlighting the role of MSCs as therapeutic target of currently applied biophysical treatments.
authors.affiliation: IRCCS Galeazzi Orthopaedic Institute, Via R. Galeazzi 4, 20161, Milan, Italy.|Department of Biotechnology and Biosciences, University of Milano-Bicocca, Milan, Italy.
authors.forename: Marco
authors.initials: M
authors.lastname: Viganò
authors.affiliation: IRCCS Galeazzi Orthopaedic Institute, Via R. Galeazzi 4, 20161, Milan, Italy.|Department of Biomedical Science for Health, University of Milan, Milan, Italy.
authors.forename: Valerio
authors.initials: V
authors.lastname: Sansone
authors.affiliation: ESWT Center, Rehabilitation Department, Humanitas Research Hospital, Rozzano, Milan, Italy.
authors.forename: Maria Cristina
authors.initials: MC
authors.lastname: d'Agostino
authors.affiliation: IRCCS Galeazzi Orthopaedic Institute, Via R. Galeazzi 4, 20161, Milan, Italy.
authors.forename: Pietro
authors.initials: P
authors.lastname: Romeo
authors.affiliation: IRCCS Galeazzi Orthopaedic Institute, Via R. Galeazzi 4, 20161, Milan, Italy.|Department of Drug Sciences, University of Pavia, Pavia, Italy.
authors.forename: Carlotta
authors.initials: C
authors.lastname: Perucca Orfei
authors.affiliation: IRCCS Galeazzi Orthopaedic Institute, Via R. Galeazzi 4, 20161, Milan, Italy. laura.degirolamo@grupposandonato.it.
authors.forename: Laura
authors.initials: L
authors.lastname: de Girolamo
mesh_terms: D000818:Animals; D055592:Biophysical Phenomena / Q000502:physiology; D049109:Cell Proliferation / Q000502:physiology*; D006801:Humans; D045164:Mesenchymal Stem Cell Transplantation / Q000379:methods*; D059630:Mesenchymal Stem Cells / Q000502:physiology*; D009140:Musculoskeletal Diseases / Q000503:physiopathology* / Q000628:therapy*; D044968:Regenerative Medicine / Q000379:methods; D016896:Treatment Outcome
keywords: ESWT; Electromagnetic fields; Mesenchymal stem cells; PEMF; Pericytes; Shock waves