International Journal of Stem Cell Research and Transplantation. 2014 © 69 EL-Wahab DA, et al. (2014). Effect of Snake Venom Disintegrin like domain on the Homing of Mesenchymal Stem Cells, Int J Stem Cell Res Transplant, 02(03), 69-77. International Journal of Stem Cell Research and Transplantation (IJST) ISSN: 2328-3548 Effect of Snake Venom Disintegrin like domain on the Homing of Mesenchymal Stem Cells Research Article EL-Wahab DA 1* , Zaki WS 1 , Habib EK 2 , Basheer AR 1 , Farid TM 1,3 , Hanaa EL.T. Nasser 1 , EL-Asmar MF 1 1 Medical Biochemistry Department, Faculty of Medicine, Ain-Shams University, Cairo, Egypt. 2 Anatomy Department, Faculty of Medicine, Ain-Shams University, Cairo, Egypt. 3 Clinical Biochemistry Department, Faculty of Medicine, King Abdul-Aziz University, Saudi Arabia. *Corresponding Author: Dalia Abd EL-Wahab, Medical Biochemistry Department, Faculty of Medicine, Ain Shams University, Egypt. E-mail: dolly.wahab@hotmail.com Received: May 07, 2014 Accepted: May 24, 2014 Published: May 28, 2014 Citation: EL-Wahab DA, et al. (2014). Effect of Snake Venom Disinte- grin like domain on the Homing of Mesenchymal Stem Cells, Int J Stem Cell Res Transplant, 02(03), 69-77. Copyright: EL-Wahab DA © 2014. This is an open-access article dis- tributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution and reproduction in any me- dium, provided the original author and source are credited. Introduction Stem cell therapy looks attractive for its potential to support tissue regeneration as requiring minimally invasive procedures with few complications [1]. The major problem in the ield of cell-based therapies is the delivery of the cells to the site of injury, a process termed homing. Molecular mechanisms underlying stem cells mi- gration and homing into the injured tissues are still poorly under- stood [2]. Migration and homing of MSCs to the injured tissues require the right combination of signaling molecules from the in- jured tissue and the corresponding receptors on MSCs [3]. Many potential factors involved in stem cells migration and homing into the injured liver have been characterized, such as the Stromal Cell- Derived Factor-1[SDF-1]/CXCR4 axis, the proteolytic enzymes matrix metalloproteinase [MMPs], the hepatocytes growth factor [HGF] and the stem cell factor [SCF]. Many researches focused on approaches that can increase the eficiency of stem cell hom- ing [4]. Disintegrin are small cysteine-rich non-enzymatic proteins that are generated by the proteolytic processing of larger precursor of snake venom metalloproteinase [5]. They have been found to inhibit platelet aggregation, angiogenesis, metastasis and tumor growth [6]. The value of the puriied Disintegrin fraction from Cerastes cerastes venom was studied. It was found that it has a hepato-protective effect in white albino mice model treated with CCl 4 . This hepato-protection role could be through up-regulation of TNF-α and HO-1 genes expression in the liver [7]. Mesenchymal stem cells can be obtained from bone marrow, ad- ipose tissue and umbilical cord blood. It can play a supportive role in organ regeneration processes [8]. Liver stem cell research promises to improve the outcomes of liver diseases and lead to new cell therapies [9]. MSCs have a potential therapeutic effect against liver ibrosis through their effect in minimizing collagen deposition in addition to their capacity to differentiate into hepat- ocytes in vitro and in vivo [10]. Also, it can mediate liver repair by releasing speciic cytokines and growth factors that modulate the activity of tissue-speciic cells, suppress local inlammation, and inhibit ibrosis and apoptosis, thereby facilitating liver regenera- tion [11,12]. TNF-α is a potent pro-inlammatory cytokine exerting pleiotropic effects on various cell types [13]. It participates in liver repair and regeneration following toxic damage [14]. HO-1 is an enzyme that catalyzes the rate-limiting step in oxi- Abstract Mesenchymal stem cells have many advantages as grafts for cell transplantation. The homing of MSCs after systemic infusion is still poorly understood. This report explored the effect of the combination of BM-MSCs with Disintegrin like fraction obtained from Cerastes cerastes crude venom on the ibrotic liver of CCl 4 treated mice. It was observed that Disintegrin like fraction could increase homing of BM-MSCs labeled with the PKH26 into the liver tissue of CCl 4 treated mice. A signiicant decrease in AST and ALT serum levels after administration of Disintegrin like fraction and/or BM-MSCs in CCl 4 treated mice were detected. VEGF was expressed in mice injected with CCl 4 alone, followed by Disintegrin like fraction or both Disintegrin like fraction and BM-MSCs. β- catenin was expressed in mice injected with CCl 4 alone, followed by BM-MSCs or both BM-MSCs and Disintegrin like fraction. Caspase-3 gene was expressed in CCl 4 treated mice injected with BM-MSCs or both BM-MSCs and Disin- tegrin like fraction. TNF-α and HO-1 were expressed in all groups. Administration of Disintegrin like fraction and / or BM-MSCs improved the histo-pathological picture and showed signs of regeneration in CCl 4 induced liver ibrosis. In conclusion, Disintegrin like fraction could increase homing of BM-MSCs into the liver tissue of CCl 4 treated mice. Further studies need to be done to explore the mechanism of homing caused by Disintegrin. KeyWords: Disintegrin Fraction; BM-MSCs; CCl 4 ; TNF-α, HO-1, VEGF, β-catenin; Caspase 3.