Research Article Sorafenib and Mesenchymal Stem Cell Therapy: A Promising ApproachforTreatmentofHCC Saieh Hajighasemlou, 1,2 Mohsen Nikbakht, 3 Saeedreza Pakzad, 2 SamadMuhammadnejad, 4 SafooraGharibzadeh, 5 MiladMirmoghtadaei, 6 FaribaZafari, 7 Iman Seyhoun, 1 JafarAi, 1 andJavadVerdi 1 1 Tehran University of Medical Sciences (TUMS), Tissue Engineering & Applied Cell Sciences, Tehran, Iran 2 Iran Ministry of Health and Medical Education, Food and Drug Control Laboratory (FDCL), Tehran, Iran 3 Tehran University of Medical Sciences, Hematology, Oncology & Stem Cell Transplantation Research Center, Tehran, Iran 4 Tehran University of Medical Sciences (TUMS), Cancer Biology Research Center Tehran, Tehran, Iran 5 Pasteur Institute of Iran, Department of Epidemiology and Biostatistics, Research Centre for Emerging and Reemerging Infectious Diseases, Tehran, Iran 6 Tehran University of Medical Sciences (TUMS), Tehran, Iran 7 Qazvin University of Medical Science, Cellular and Molecular Research Center, Qazvin, Iran Correspondence should be addressed to Javad Verdi; javad0verdi@gmail.com Received 22 January 2020; Revised 6 May 2020; Accepted 21 May 2020; Published 15 June 2020 AcademicEditor:JaeYoulCho Copyright©2020SaiehHajighasemlouetal.isisanopenaccessarticledistributedundertheCreativeCommonsAttribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. Hepatocellular carcinoma (HCC) is the fifth most commonly diagnosed cancer and the second most common cause of cancer- related death worldwide. Sorafenib (Sora) is used as a targeted therapy for HCC treatment. Mesenchymal stem cells (MSCs) are appliedasanewapproachtofightmalignancies.DrugresistanceandsideeffectsarethemajorconcernswithSoraadministration. eeffectofusingthecombinationofsorafenibandMSCsontumorregressioninxenograftHCCmodelswasevaluatedinthis study. Methods and Materials.Humanhepatocellularcarcinomacelllines(HepG2)weresubcutaneouslyimplantedintotheflank of18nudemice.eanimalswererandomlydividedintosixgroups(n � 3);eachreceivedSora(oral),MSCs(IVinjection),MSCs (localinjection),Sora+MSCs(IVinjection),Sora+MSCs(localinjection),ornotreatment(thecontrolgroup).Sixweeksafter tumor implantation, the mice were scarified and tumoral tissues were resected in their entirety. Histopathological and im- munohistochemicalevaluationswereusedtomeasuretumorproliferationandangiogenesis.Apoptoticcellswerequantifiedusing the TUNEL assay. Results. No significant difference was found in the tumor grade among the treatment groups. Differentiation features of the tumoral cells were histopathologically insignificant in all the groups. Tumor necrosis was highest in the hpMSC (local)+Soragroup.TumorcellproliferationwasreducedinhpMSC(local)+Sora-treatedandhpMSC(IV)+Sora-treatedmice compared with the other groups. Apoptotic-positive cells occupied a greater proportion in the Sora, hpMSC (IV)+Sora, and hpMSC (local)+Sora groups. Conclusion. A combination of chemotherapy and MSC can yield to more favorable results in the treatment of HCC. 1.Introduction HCC is the fifth most common malignant tumor and contributes to about 800,000 deaths globally per annum [1–3]. Only a small fraction of patients with HCC are candidates for curative treatments, such as surgical resection, liver transplantation, or radiofrequency ablation [4].Althoughnumerousnovelstrategieshavebeenproposed to treat HCC [5], including cell-based therapies, the disease remains challenging to combat. Sorafenib is the only FDA-approved drug that is ad- ministered as the first line systemic therapy in advanced Hindawi Evidence-Based Complementary and Alternative Medicine Volume 2020, Article ID 9602728, 8 pages https://doi.org/10.1155/2020/9602728