title: Premise and promise of mesenchymal stem cell-based therapies in clinical vascularized composite allotransplantation.
abstract: OBJECTIVE
  Over the past decade, clinical vascularized composite allotransplantation (VCA) has enabled functional and quality of life restoration in a wide range of indications secondary to devastating tissue loss. However, the spectre of toxicity and long-term complications of chronic immunosuppression has curtailed the momentum of VCA. This study summarizes the literature evidence behind successful mesenchymal stem cell (MSC)-based cell therapies highlighting their multipronged immunomodulatory, restorative and regenerative characteristics with special emphasis towards VCA applications.
  
  
  RESULTS
  Experimental and clinical studies in solid organs and VCA have confirmed that MSCs facilitate immunosuppression-free allograft survival or tolerance, stimulate peripheral nerve regeneration, attenuate ischaemia-reperfusion injury, and improve tissue healing after surgery. It has been hypothesized that MSC-induced long-term operational tolerance in experimental VCA is mediated by induction of mixed donor-specific chimerism and regulatory T-cell mechanisms. All these characteristics of MSCs could thus help expand the scope and clinical feasibility of VCA.
  
  
  CONCLUSIONS
  Cellular therapies, especially those focusing on MSCs, are emerging in solid organ transplantation including VCA. Although some clinical trials have begun to assess the effects of MSCs in solid organ transplantation, much scientific domain remains uncharted, especially for VCA.
authors.affiliation: aDepartment of Plastic Surgery and Hand Surgery, University Hospital Zurich (USZ), Switzerland bDepartment of Plastic Surgery, University of Pittsburgh Medical Center (UPMC), cMcGowan Institute for Regenerative Medicine, University of Pittsburgh, Pennsylvania, USA.
authors.forename: Riccardo
authors.initials: R
authors.lastname: Schweizer
authors.forename: Vijay S
authors.initials: VS
authors.lastname: Gorantla
authors.forename: Jan A
authors.initials: JA
authors.lastname: Plock
mesh_terms: D000818:Animals; D006084:Graft Rejection / Q000276:immunology; D006801:Humans; D007108:Immune Tolerance; D045164:Mesenchymal Stem Cell Transplantation; D059630:Mesenchymal Stem Cells; D014184:Transplantation, Homologous; D063986:Vascularized Composite Allotransplantation