Effect of Human Bone Marrow-Mesenchymal Stem Cells Conditioned media on KGF and TGF-β1 Genes Expression in Diabetic Rats Wound

Background: Wound healing is a complex process that is impaired in diabetic patients due to several factors. So far, the positive effects of mesenchymal stem cells secretions in wound healing process have been reported. In this study, we investigated the effect of human mesenchymal stem cells Conditioned media on expression of effective factors involved in wound healing. Materials and Methods: 27 rats were divided into 5 groups: no wound control, normal control, diabetic control, diabetic placebo and diabetic experimental. Diabetes was induced by Alloxan. A wound was created on the back of the rats. Then, the conditioned medium was prepared from mesenchymal stem cells. Diabetic experimental rats received 200 microliter of conditioned medium intravenously. The wounds were sampled and expression of KGF and TGF-β1 genes was examined by RT-PCR on days four and seven after wounding. Results: In the diabetic experimental group, expression of KGF gene at fourth and seventh days had been non-significantly increased in comparison to diabetic control group. While, expression of TGF-β1 gene in diabetic experimental group compared to diabetic control group had been significantly (p<0.05) increased on fourth day, and non-significantly increased on seventh day. Conclusion: It seems that using the conditioned medium derived from human mesenchymal stem cells positively affects the expression of trophic and inflammatory factors involved in diabetic skin wound healing.

[1]  M. Bayat,et al.  Histological and gene expression analysis of the effects of pulsed low-level laser therapy on wound healing of streptozotocin-induced diabetic rats , 2014, Lasers in Medical Science.

[2]  Bayat Mohammad,et al.  The effect of human bone marrow-mesenchymal stem cells secretoms on diabetic wound healing , 2014 .

[3]  Amarpal,et al.  Therapeutic Potential of Canine Bone Marrow Derived Mesenchymal Stem Cells and its Conditioned Media in Diabetic Rat Wound Healing , 2013 .

[4]  H. Hsu,et al.  Mesenchymal stem cell‐conditioned medium facilitates angiogenesis and fracture healing in diabetic rats , 2012, Journal of tissue engineering and regenerative medicine.

[5]  S. Cheong,et al.  Induced pluripotent stem cells in research and therapy. , 2012, The Malaysian journal of pathology.

[6]  Ching‐Jen Wang,et al.  Bone Marrow–Derived Mesenchymal Stem Cells Enhanced Diabetic Wound Healing through Recruitment of Tissue Regeneration in a Rat Model of Streptozotocin-Induced Diabetes , 2011, Plastic and reconstructive surgery.

[7]  Shih-Hwa Chiou,et al.  Enhancement of Wound Healing by Human Multipotent Stromal Cell Conditioned Medium: The Paracrine Factors and p38 MAPK Activation , 2011, Cell transplantation.

[8]  T. Ritter,et al.  Immunological aspects of allogeneic mesenchymal stem cell therapies. , 2010, Human gene therapy.

[9]  R. Abdi,et al.  The Mobilization and Effect of Endogenous Bone Marrow Progenitor Cells in Diabetic Wound Healing , 2010, Cell transplantation.

[10]  J. Moon,et al.  Secretory profiles and wound healing effects of human amniotic fluid-derived mesenchymal stem cells. , 2010, Stem cells and development.

[11]  Hyung-Min Chung,et al.  Potential application of adipose-derived stem cells and their secretory factors to skin: discussion from both clinical and industrial viewpoints , 2010, Expert opinion on biological therapy.

[12]  S. Dulchavsky,et al.  Treatment with bone marrow‐derived stromal cells accelerates wound healing in diabetic rats , 2008, International wound journal.

[13]  Liwen Chen,et al.  Paracrine Factors of Mesenchymal Stem Cells Recruit Macrophages and Endothelial Lineage Cells and Enhance Wound Healing , 2008, PloS one.

[14]  R. Burt,et al.  Clinical applications of blood-derived and marrow-derived stem cells for nonmalignant diseases. , 2008, JAMA.

[15]  Oscar Ochoa,et al.  Chemokines and Diabetic Wound Healing , 2007, Vascular.

[16]  Paul G Scott,et al.  Mesenchymal Stem Cells Enhance Wound Healing Through Differentiation and Angiogenesis , 2007, Stem cells.

[17]  Andrea T. Badillo,et al.  Treatment of diabetic wounds with fetal murine mesenchymal stromal cells enhances wound closure , 2007, Cell and Tissue Research.

[18]  S. Dulchavsky,et al.  Wound repair by bone marrow stromal cells through growth factor production. , 2006, The Journal of surgical research.

[19]  Vincent Falanga,et al.  Wound healing and its impairment in the diabetic foot , 2005, The Lancet.

[20]  Paul G Scott,et al.  Pathophysiology of chronic nonhealing wounds. , 2005, The Journal of burn care & rehabilitation.

[21]  G. Saed,et al.  Transforming Growth Factors β1, β2 and β3 and their Receptors are Differentially Expressed in Human Peritoneal Fibroblasts in Response to Hypoxia , 2002 .

[22]  G. Ashcroft Bidirectional regulation of macrophage function by TGF-β , 1999 .

[23]  S. Werner,et al.  Induction of keratinocyte growth factor expression is reduced and delayed during wound healing in the genetically diabetic mouse. , 1994, The Journal of investigative dermatology.

[24]  Baharvand Hossein,et al.  The Role of Ultraweb Nano-Fibrillar Substrates in the Differentiation of In Vitro Mouse Bone Marrow Mesenchymal Stem Cell-Derived Hepatocyte-Like Cells , 2010 .

[25]  A. Hardikar,et al.  Mesenchymal stem cells derived from bone marrow of diabetic patients portrait unique markers influenced by the diabetic microenvironment. , 2009, The review of diabetic studies : RDS.