Understanding the mechanism of radiation induced fibrosis and therapy options.

Radiation therapy has been increasingly employed as a tool to cure and palliate majority of solid tumors. Although radiotherapy has shown promising results in preserving structure and function of organs, it is associated with late side effects mainly manifested in the form of tissue fibrosis. Recent advances in molecular biology techniques has helped better understand the molecular mechanisms involved in radiation induced fibrosis. Currently, very few treatment modalities are available to treat the condition with moderate success rate. Stem cell therapies and particularly adipose tissue and adipose derived stem cells therapies have shown promising results in clinical applications. Identification of the key factors involved in the mitigation process will help to enhance the beneficial effects and develop new therapy approaches.

Adipose- and Bone Marrow-Derived Mesenchymal Stem Cells Prolong Graft Survival in Vascularized Composite Allotransplantation.

BACKGROUND: Strategies aiming at minimization or elimination of systemic immunosuppression are key immediate goals for clinical expansion of vascularized composite allotransplantation (VCA). We compared the in vitro and in vivo immunomodulatory efficacy of adipose-derived mesenchymal stem cells (AD-MSCs) and bone marrow (BM)-derived MSCs in a rat VCA model. METHODS: Both cell types were tested in vitro for suppressor function using mixed lymphocyte reactivity assays. AD-MSCs or BM-MSCs were administered intravenously (1 × 10 or 5 × 10 cells/animal) to Lewis rat recipients of mismatched Brown Norway hindlimb transplants. Short course tacrolimus (FK-506) monotherapy was withdrawn at postoperative day 21. In vivo regulatory T-cell induction, peripheral blood chimerism, and microchimerism in lymphatic organs were analyzed. RESULTS: AD-MSCs and BM-MSCs exhibited strong dose-dependent suppressor function in vitro, which was significantly more pronounced for AD cells. In vivo, all animals revealed peripheral multi-lineage chimerism at four weeks (P < 0.01) independent of cell type and dosage. Regulatory T-cell levels were increased with both cell types, the most in AD-MSC groups. These immunomodulatory effects were only transient. MSC treatment resulted in long-term (>120 day) allograft survival in 47% of the animals, which correlated with durable microchimerism in BM and spleen. CONCLUSIONS: AD-MSCs and BM-MSCs exert immunomodulatory effects that prolong survival of immunogenic skin-bearing VCA grafts with short course (21 day) tacrolimus induction therapy. The in vivo findings in terms of allograft survival did not reflect superior immunomodulatory characteristics of AD-MSCs found in vitro.