A STUDY ON THE EFFECT OF POLY (I: C) VS LPS ON STIMULATEING BONE MARROW-DERIVED MESENCHYMAL CELLS IN HEALING THIRD-DEGREE SKIN BURNS IN MOUSE

The positive effect of mesenchymal stem cells in healing of various types of tissue
damage such as burn has been reported. The therapeutic potential effects of mesenchymal stem cells
influenced by certain agonists from their surface called Toll like receptor (TLR) can be modified into
proinflammatory and anti-inflamation phenotypes. It is believed that modification of phenotypes of
mesenchymal stem cells can affect their therapeutic function. Therefore, the aim of this study was to assess
the influence of Poly(I:C) (TLR3 agonist) versus LPS (TLR4 agonist) in stimulating mesenchymal stem cells
and alteration of the therapeutic potential of these cells for the treatment of third-degree skin burns in mice
which was performed at institute of Bio-technology, Urmia University, Urmia, Iran.
Materials & Methods: Total 36 male mice aged 7-8 weeks with 25-30 gr average weights were selected.
Based on burn standard method, a stainless-metal rod was heated to 100 in boiling water and burn wounds
of 9 second duration were created on each mouse. Within an hour of burn induction, the mice were randomly
assigned to four groups, control group with daily application of silver sulfadiazine gel, treatment 1 was treated
by receiving subcutaneously 106 unstimulated mesenchymal cells, treatment 2 was treated by receiving
subcutaneously 106 lipopolysaccharide (LPS)-stimulated mesenchymal cells, treatment3 was treated by
receiving subcutaneously 106 Poly (I:C)-stimulated mesenchymal cells. Biopsies were taken from wounds
and some normal tissues around it on days 7, 14 and 21 after burn induction. All samples were examined
histopathologically by Hematoxilin-Eosin and masson trichrome stains in terms of thickness of the
granulation tissue, tissue repair process, array of granulation tissue and deposition of collagen fibers in the
repairing area. Checking normality test was processed using SPSS 18.0 Software (SPSS Inc, Chicago, IL,
USA) and data then were analyzed using one-way ANOVA, Tukey and post hoc test.
Results: Thickness of the granulation tissue on day 7 differed significantly between the control group and
treatment 1 (P </ 007) as well as control group and the treatment 2 (P </ 001). Moreover, treatment 2 showed
statistically significant difference for creating the most extensive granulation tissue compared with treatment
3 (P</002). Thickness of granulation tissue started to decrease since day 7 in all treatment groups but control
with a more significant progress in treatment 2. The minimum thickness of the granulation tissue was
observed for treatment 2 on day 21. The results from the hematoxylin & eosin and Masson's trichrome stained
granulation tissues revealed collagen deposition develop in the repairing area
Conclusion: Increased therapeutic potential of LPS -stimulated mesenchymal stem cells versus reduced
therapeutic potential of Poly (I:C)-stimulated mesenchymal stem cells can be as a result of attaining the
proinflammatory versus anti-inflammatory phenotype in mesenchymal stem cells in response to the
respective agonists, respectively