title: Cell-free derivatives from mesenchymal stem cells are effective in wound therapy.
abstract: OBJECTIVE
  To compare the efficacy of cell-free derivatives from Bone marrow derived human mesenchymal stem cells (hMSCs) in wound therapy.
  
  
  METHODS
  hMSCs have been shown to play an important role in wound therapy. The present study sought to compare efficacy of hMSCs and cell-free derivatives of hMSCs, which may be clinically more relevant as they are easier to prepare, formulate and transport. hMSCs were isolated from human bone marrow and cultured. Multi lineage differentiation of hMSCs was performed to confirm their identity. The ability of hMSCs to migrate was evaluated using in vitro and in vivo migration assays. Cell lysates and conditioned medium concentrate was prepared from hMSCs (see Methods for details). Wounds were induced in mice and wound areas were measure before and after cell and cell-free derivative treatment. RNA and proteins were extracted from the skin and cytokine levels were measured.
  
  
  RESULTS
  Co-culture of hMSCs with keratinocytes resulted in increased expression of CXCL-12 (SDF1) and ENA78 (CXCL-5) in the conditioned media indicating that the hMSCs can respond to signals from keratinocytes. Accelerated wound closure was observed when hMSCs were injected near the site of excisional wounds in athymic as well as NOD/SCID mice. Interestingly, cell-free lysates prepared from hMSCs were also effective in inducing accelerated wound closure and increased expression of SDF1 and CXCL-5 at the wound bed. Additionally, concentrated media from hMSCs as well as an emulsion containing lysates prepared from hMSCs was also found to be more effective in rapid re-epithelialization than fibroblasts or vehicle-alone control. Use of cell-free derivatives may help replace expensive wound care approaches including use of growth factors, epidermal/dermal substitutes, synthetic membranes, cytokines, and matrix components, and most importantly avoid transmission of pathogens from human and animal products.
  
  
  CONCLUSIONS
  These results encourage development of derivatives of hMSCs for wound care and re-epithelialization applications.
authors.affiliation: Pravin J Mishra, Prasun J Mishra, Laboratory of Cancer Biology and Genetics, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892-4264, United States.
authors.forename: Pravin J
authors.initials: PJ
authors.lastname: Mishra
authors.forename: Prasun J
authors.initials: PJ
authors.lastname: Mishra
authors.forename: Debabrata
authors.initials: D
authors.lastname: Banerjee