Abtahi Froushani Sm, Delirezh N, Hobbenaghi R, Mosayebi Gh,
Volume 69, Issue 11 (4 2012)
Abstract
Background: Recent studies have demonstrated an essential role for IL-17 in the pathogenesis of experimental autoimmune encephalomyelitis (EAE). Furthermore, it has been shown that FoxP3+Treg cells play an important role in the suppression of autoinflammatory reactions. Although, previous studies have determined the immunomodulatory potentials of all-trans-retinoic acid (ATRA), but these immunomodulations have been mostly justified by alteration in Th1/Th2 cytokines. The present study was carried out to investigate the therapeutic effects of ATRA on EAE and its effects on T-helper cells responses.
Methods: EAE was induced by MOG35-55 peptide and complete Freund's adjuvant in female C57BL/6 mice. The mice were allocated to two therapeutic groups (n=7 per group). Treatment with ATRA (500 μg/mouse every other day) was initiated in treatment group on day 12 when they developed a disability score. EAE controls received vehicle alone with the same schedule. Signs of disease were recorded daily until day 33 when the mice were sacrificed. Splenocytes were tested for proliferation by MTT test, cytokine production by ELISA and FoxP3+Treg cell frequency by flowcytometry.
Results: ATRA significantly reduced the clinical signs of established EAE. Aside from decreasing lymphocytic proliferation (P<0.05), ATRA significantly inhibited the production of pro-inflammatory IL-17 (P<0.005) as well as IFN-γ (P<0.0005) upon antigen-specific restimulation of splenocytes. FoxP3+Treg cell frequency and IL-10 levels were not altered significantly. However, IFN-γ to IL-10 and IL-17 to IL-10 ratios decreased significantly (P<0.0005).
Conclusion: Parallel to reducing autoreactive lymphocyte proliferation and cytokine production in favor of pro-inflammatory cytokines, all-trans-retinoic acid ameliorated established experimental autoimmune encephalomyelitis.
Leyla Soleymani , Rahim Hobbenaghi , Aram Mokarizadeh , Samad Zare , Nowruz Delirezh ,
Volume 72, Issue 7 (October 2014)
Abstract
Background: Recently, bone-marrow-derived cells have introduced new therapeutic approaches to the management of wound healing in severe skin injuries. Bone marrow-derived stromal cells are described as a heterogeneous population, including mesenchymal stem cells, hematopoietic stem cells, and fibro-blast cells. Results derived from several studies indicate that these cells may contribute to tissue regeneration whether through producing variety of bioactive growth factors and/or by differentiation into mesoderm lineage. The aim of the present study was to investigate the effect of subcutaneous administration of bone marrow-derived stromal cells in repairing or regeneration of skin wounds induced by third-degree burn in a mouse model.
Methods: In an experimental study that was performed in Urmia University research center from December 2011 to June 2012, The third-degree skin burn was induced on the shaved backs of healthy 7-8 week old male mice (N=18) using a metal rods heated in boiling water. After 1 hour, based on the equal physical condition mice were randomly divided into two separate groups and then subcutaneously administered with phosphate buffered saline (PBS 400 µl) or bone marrow-derived stromal cells (106 cell in 400µl PBS) at the burn site. 7, 14 and 21 days after induction of burn injury, biopsies were taken from burn wounds and then the sections were prepared. Subsequently the prepared sections were stained with hematoxylin/eosin and Masson's trichrome to explore histopathological changes evoke by administration of bone marrow derived stromal cells in comparison with control subjects.
Results: Considering investigated parameters including formation of granulation tissue (respectively on days 7, 14 and 21 P≤ 0/007, P≤ 0/0013 and P≤ 0/001), angiogenesis (on day 21 P≤ 0/002) and collagen deposition, in mice treated with bone marrow-derived stromal cells the rate of healing of third-degree thermal burns was significantly accelerated when compared to the PBS-treated mice.
Conclusion: This experimental modulation of wound healing suggests that bone marrow-derived stromal cells can significantly enhance the rate of wound healing possibly through stimulation of granulation tissue, angiogenesis, fibroblast proliferation and collagen deposition.
