A Meta-Analysis of the Ultimate Effect of Mesenchymal Stem / Stromal Cell in Tumor Animal Models

Pratika Yuhyi Hernanda

Abstract


Several studies have reported the Mesenchymal Stem Cell (MSC) triggered and inhibited tumor growth. We therefore performed a systematic review and meta-analysis of experimental studies evaluating the effects of MSC on tumors. Method: We collected the relevant studies by searching ProQuest, PubMed Publisher, and GoogleScholar. A meta-analysis was performed for the outcome measure: tumor volume and tumor weight. The search resulted in 440 references, of which 22 could be included in the meta-analysis. Of these 22 experiments, 18 (40%) showed a significant decrease of tumor growth and 27 (60%) experiments showed a significant increase of tumor growth. The engineered MSC and the late phase of MSC injection have a significant contribution to tumor inhibition effect. The meta-analysis showed that there are no significant effect of mesenchymal stem cell therapy to the tumor animal volume (SMD-0.23[-0.55, 0.09]; n=15), and to the tumor animal weight (SMD -0.19 [-0.77,0.39]; n=7). Conclusion: MSC appears to have a relative dependent effect in animal models.

 


Keywords


mesenchymal stem cell; tumor animal model

Full Text:

PDF

References


Abdel aziz MT, El Asmar MF, Atta HM, Mahfouz S, Fouad HH et al, 2011. Efficacy of mesenchymal stem cells in suppression of hepatocarcinorigenesis in rats: possible role of Wnt signaling. J Exp Clin Cancer Res. 30(1): 49.

Ahn J, Lee H, Seo K, Kang S, Ra J, Youn H, 2013. Anti-tumor effect of adipose tissue derived-mesenchymal stem cells expressing interferon-beta and treatment with cisplatin in a xenograft mouse model for canine melanoma. PLoS One. 8(9): e74897.

Balyasnikova IV, Ferguson SD, Sengupta S, Han Y, Lesniak MS, 2010. Mesenchymal stem cells modified with a single-chain antibody against EGFRvIII successfully inhibit the growth of human xenograft malignant glioma. PloS one. 5(3): e9750.

Bassi G, Guilloton F, Menard C, Di Trapani M, Deschaseaux F et al, 2014. Effects of a ceramic biomaterial on immune modulatory properties and differentiation potential of human mesenchymal stromal cells of different origin. Tissue Eng Part A. 21(3-4): 767-781.

Beckermann BM, Kallifatidis G, Groth A, Frommhold D, Apel A et al, 2008. VEGF expression by mesenchymal stem cells contributes to angiogenesis in pancreatic carcinoma. Br J Cancer. 99(4): 622-631.

Bianchi G, Morandi F, Cilli M, Daga A, Bocelli-Tyndall C et al, 2012. Close interactions between mesenchymal stem cells and neuroblastoma cell lines lead to tumor growth inhibition. PloS one. 7: e48654.

Cavallari C, Fonsato V, Herrera M, Bruno S, Tetta C, Camussi G, 2013. Role of Lefty in the anti tumor activity of human adult liver stem cells. Oncogene. 32: 819-826.

Chen X, Liu B, Li Q, Honorio S, Liu X et al, 2013. Dissociated primary human prostate cancer cells coinjected with the immortalized Hs5 bone marrow stromal cells generate undifferentiated tumors in NOD/SCID-γ mice. PloS one. 8: e56903.

Cousin B, Ravet E, Poglio S, De Toni F, Bertuzzi M et al, 2009. Adult stromal cells derived from human adipose tissue provoke pancreatic cancer cell death both in vitro and in vivo. PloS one. 4: e6278.

De Boeck A, Hendrix A, Maynard D, Van Bockstal M, Daniels A et al, 2013. Differential secretome analysis of cancer-associated fibroblasts and bone marrow-derived precursors to identify microenvironmental regulators of colon cancer progression. Proteomics. 13 (2): 379-388.

de Melo SM, Bittencourt S, Ferrazoli EG, da Silva CS, da Cunha FF et al, 2015. The anti-tumor effects of adipose tissue mesenchymal stem cell transduced with HSV-Tk gene on U-87-driven brain tumor. PLoS One. 10: e0128922.

Du T, Ju G, Wu S, Cheng Z, Cheng J et al, 2014. Microvesicles derived from human Wharton's jelly mesenchymal stem cells promote human renal cancer cell growth and aggressiveness through induction of hepatocyte growth factor. PloS one. 9: e96836.

Galie M, Konstantinidou G, Peroni D, Scambi I, Marchini C et al, 2008. Mesenchymal stem cells share molecular signature with mesenchymal tumor cells and favor early tumor growth in syngeneic mice. Oncogene. 27(18): 2542-2551.

Gao P, Ding Q, Wu Z, Jiang H, Fang Z, 2010a. Therapeutic potential of human mesenchymal stem cells producing IL-12 in a mouse xenograft model of renal cell carcinoma. Cancer letters. 290(2): 157-166.

Gao Y, Yao A, Zhang W, Lu S, Yu Y et al, 2010b. Human mesenchymal stem cells overexpressing pigment epithelium-derived factor inhibit hepatocellular carcinoma in nude mice. Oncogene. 29(19):2784-2794.

Gong P, Wang Y, Wang Y, Jin S, Luo H et al, 2013. Effect of bone marrow mesenchymal stem cells on hepatocellular carcinoma in microcirculation. Tumour Biol. 34(4): 2161-2168.

Hanahan D and Weinberg RA, 2011. Hallmarks of cancer: the next generation. Cell. 144(5): 646-674.

Hernanda PY, Pedroza-Gonzales A, van der Laan LJW, Janssen HLA, Peppelenbosch MP, Pan Q, 2013a. Human Liver Carcinomas Recruit Mesenchymal Stem/Stromal Cells That Can Promote Tumor Growth Via Paracrine Signaling. Journal of Hepatology. 58: S431-S431.

Hernanda PY, Pedroza-Gonzalez A, Sprengers D, Peppelenbosch MP, Pan Q, 2014. Multipotent mesenchymal stromal cells in liver cancer: implications for tumor biology and therapy. Biochim Biophys Acta. 1846(2): 439-445.

Hernanda PY, Pedroza-Gonzalez A, van der Laan LJ, Broker ME, Hoogduijn MJ et al, 2013b. Tumor promotion through the mesenchymal stem cell compartment in human hepatocellular carcinoma. Carcinogenesis. 34: 2330-2340.

Hernanda PY, Pedroza-Gonzalez A, van der Laan LJ, Bröker ME, Hoogduijn MJ et al, 2013c. Tumor promotion through the mesenchymal stem cell compartment in human hepatocellular carcinoma. Carcinogenesis. 34: 2330-2340.

Huang F, Wang M, Yang T, Cai J, Zhang Q et al, 2014a. Gastric cancer-derived MSC-secreted PDGF-DD promotes gastric cancer progression. Journal of cancer research and clinical oncology. 140: 1835-1848.

Huang F, Wang M, Yang T, Cai J, Zhang Q et al, 2014b. Gastric cancer-derived MSC-secreted PDGF-DD promotes gastric cancer progression. J Cancer Res Clin Oncol. 140: 1835-1848.

Kang N, Hwang K, Yi B, Lee H, Jeung E et al, 2012. Human amniotic fluid-derived stem cells expressing cytosine deaminase and thymidine kinase inhibits the growth of breast cancer cells in cellular and xenograft mouse models. Cancer gene therapy. 19(6): 412-419.

Karnoub AE, Dash AB, Vo AP, Sullivan A, Brooks MW et al, 2007. Mesenchymal stem cells within tumour stroma promote breast cancer metastasis. Nature. 449(7162): 557-563.

Klopp AH, Gupta A, Spaeth E, Andreeff M, Marini F 3rd, 2011. Concise review: Dissecting a discrepancy in the literature: do mesenchymal stem cells support or suppress tumor growth?. Stem Cells. 29(1): 11-9.

Lee JS, Lee JM, Im GI, 2011. Electroporation-mediated transfer of Runx2 and Osterix genes to enhance osteogenesis of adipose stem cells. Biomaterials, 32(3): 760-768.

Li GC, Ye QH, Xue YH, Sun HJ, Zhou HJ et al, 2010a. Human mesenchymal stem cells inhibit metastasis of a hepatocellular carcinoma model using the MHCC97‐H cell line. Cancer science. 101(12): 2546-2553.

Li H, Feng Z, Tsang TC, Tang T, Jia X, He X et al, 2014. Fusion of HepG2 cells with mesenchymal stem cells increases cancerassociated and malignant properties: an in vivo metastasis model. Oncol Rep. 32: 539-547.

Li L, Li S, Cai T, Wang H, Xie X et al, 2016. The targeted inhibitory effects of human amniotic fluid stem cells carrying CXCR4 promoter and DAL-1 on non-small cell lung carcinoma growth. Gene therapy. 23(2): 214.

Li T, Song B, Du X, Wei Z and Huo T, 2013a. Effect of bone-marrow-derived mesenchymal stem cells on high-potential hepatocellular carcinoma in mouse models: an intervention study. Eur J Med Res. 18(1): 34.

Liu J, Han G, Liu H, Qin C, 2013. Suppression of cholangiocarcinoma cell growth by human umbilical cord mesenchymal stem cells: a possible role of Wnt and Akt signaling. PloS one. 8: e62844.

Liu Y, Han ZP, Zhang SS, Jing YY, Bu XX et al, 2011) Effects of inflammatory factors on mesenchymal stem cells and their role in the promotion of tumor angiogenesis in colon cancer. J Biol Chem. 286: 25007-25015.

Ma Y, Hao X, Zhang S, Zhang J, 2012. The in vitro and in vivo effects of human umbilical cord mesenchymal stem cells on the growth of breast cancer cells. Breast cancer research and treatment. 133: 473-485.

Nowicka A, Marini FC, Solley TN, Elizondo PB, Zhang Ye al, 2013. Human omental-derived adipose stem cells increase ovarian cancer proliferation, migration, and chemoresistance. PloS one. 8: e81859.

Ohta N, Ishiguro S, Kawabata A, Uppalapati D, Pyle M et al, 2015. Human umbilical cord matrix mesenchymal stem cells suppress the growth of breast cancer by expression of tumor suppressor genes. PLoS One. 10: e0123756.

ok Ahn J, woo Lee H, won Seo K, keun Kang S et al, 2013. Anti-tumor effect of adipose tissue derived-mesenchymal stem cells expressing interferon-β and treatment with cisplatin in a xenograft mouse model for canine melanoma. PLoS One. 8: e74897.

Pessina A, Bonomi A, Coccè V, Invernici G, Navone S et al, 2011. Mesenchymal stromal cells primed with paclitaxel provide a new approach for cancer therapy. PLoS One. 6: e28321.

Qiao L, Xu Z, Zhao T, Zhao Z, Shi M et al, 2008. Suppression of tumorigenesis by human mesenchymal stem cells in a hepatoma model. Cell research. 18: 500.

Rhodes LV, Muir SE, Elliott S, Guillot LM, Antoon JW et al, 2010. Adult human mesenchymal stem cells enhance breast tumorigenesis and promote hormone independence. Breast cancer research and treatment. 121: 293-300.

Ryu H, Oh JE, Rhee KJ, Baik SK, Kim J et al, 2014. Adipose tissue-derived mesenchymal stem cells cultured at high density express IFN-beta and suppress the growth of MCF-7 human breast cancer cells. Cancer Lett. 352(2): 220-227.

Secchiero P, Zorzet S, Tripodo C, Corallini F, Melloni E et al, 2010. Human bone marrow mesenchymal stem cells display anti-cancer activity in SCID mice bearing disseminated non-Hodgkin's lymphoma xenografts. PloS one. 5: e11140.

Song B, Kim B, Choi SH, Song KY, Chung YG et al, 2014. Mesenchymal stromal cells promote tumor progression in fibrosarcoma and gastric cancer cells. Korean J Pathol. 48: 217-24.

Spaeth EL, Dembinski JL, Sasser AK, Watson K, Klopp A et al, 2009. Mesenchymal stem cell transition to tumor-associated fibroblasts contributes to fibrovascular network expansion and tumor progression. PloS one. 4: e4992.

Sung, SY, Liao CH, Wu HP, Hsiao WC, Wu IH et al, 2013. Loss of let-7 microRNA upregulates IL-6 in bone marrow-derived mesenchymal stem cells triggering a reactive stromal response to prostate cancer. PloS one. 8(8): e71637.

Takahara K, Ii M, Inamoto T, Komura K, Ibuki N et al, 2014. Adipose-derived stromal cells inhibit prostate cancer cell proliferation inducing apoptosis. Biochem Biophys Res Commun. 446: 1102-1107.

Waterman RS, Henkle SL, Betancourt AM, 2012. Mesenchymal stem cell 1 (MSC1)-based therapy attenuates tumor growth whereas MSC2-treatment promotes tumor growth and metastasis. PLoS One. 7: e45590.

Waterman RS, Tomchuck SL, Henkle SL, Betancourt AM, 2010. A new mesenchymal stem cell (MSC) paradigm: polarization into a pro-inflammatory MSC1 or an Immunosuppressive MSC2 phenotype. PLoS One. 5: e10088.

Wu S, Ju GQ, Du J, Zhu YJ, Liu GH, 2013. Microvesicles derived from human umbilical cord Wharton’s jelly mesenchymal stem cells attenuate bladder tumor cell growth in vitro and in vivo. PloS one. 8: e61366.

Xie C, Xie D, Lin B, Zhang G, Wang P et al, 2013. Interferon-β gene-modified human bone marrow mesenchymal stem cells attenuate hepatocellular carcinoma through inhibiting AKT/FOXO3a pathway. British journal of cancer. 109: 1198.

Xu C, Lin L, Cao G, Chen Q, Shou P et al, 2014. Interferon-alpha-secreting mesenchymal stem cells exert potent antitumor effect in vivo. Oncogene. 33: 5047-5052.

Yan XL, Jia YL, Chen L, Zeng Q, Zhou JN et al, 2013a. Hepatocellular carcinoma‐associated mesenchymal stem cells promote hepatocarcinoma progression: Role of the S100A4‐miR155‐SOCS1‐MMP9 axis. Hepatology. 57: 2274-2286.

Zhang T, Lee YW, Rui YF, Cheng TY, Jiang XH, Li G, 2013. Bone marrow-derived mesenchymal stem cells promote growth and angiogenesis of breast and prostate tumors. Stem Cell Res Ther. 4: 70.

Zhao W, Ren G, Zhang L, Zhang Z, Liu J et al, 2012. Efficacy of mesenchymal stem cells derived from human adipose tissue in inhibition of hepatocellular carcinoma cells in vitro. Cancer Biother Radiopharm. 27: 606-613.

Zhu W, Xu W, Jiang R, Qian H, Chen M et al, 2006. Mesenchymal stem cells derived from bone marrow favor tumor cell growth in vivo. Exp Mol Pathol. 80(3): 267-274.




DOI: http://dx.doi.org/10.30742/jikw.v9i1.840

Refbacks

  • There are currently no refbacks.


Copyright (c) 2020 Pratika Yuhyi Hernanda

Creative Commons License
This work is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License.

 

 Google Scholar Sinta Science and Technology Index  Indonesian Scientific Journal Database (ISJD) Indonesian Publication Index (IPI) PKP Index Garuda

 Hasil gambar untuk DOAJ

 

 





Jurnal Ilmiah Kedokteran Wijaya Kusuma 

ISSN: 1978-2071(print); 2580-5967 (online)
Fakultas Kedokteran 
Universitas Wijaya Kusuma Surabaya
Surabaya, Indonesia
 
Creative Commons License
All publications by Jurnal Ilmiah Kedokteran Wijaya Kusuma are licensed under a Creative Commons Attribution-NonCommercial 4.0 International License