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Mesenchymal stem cells combined with albendazole as a novel therapeutic approach for experimental neurotoxocariasis

Published online by Cambridge University Press:  17 March 2020

E. V. N. Beshay Open the ORCID record for E. V. N. Beshay [Opens in a new window] ,
S. A. El-Refai ,
G. S. Sadek ,
A. A. Elbadry ,
F. H. Shalan  and
A. F. Afifi
E. V. N. Beshay*
Affiliation:
Medical Parasitology Department, Faculty of Medicine, Menoufia University, Menoufia, Egypt
S. A. El-Refai
Affiliation:
Medical Parasitology Department, Faculty of Medicine, Menoufia University, Menoufia, Egypt
G. S. Sadek
Affiliation:
Medical Parasitology Department, Faculty of Medicine, Menoufia University, Menoufia, Egypt
A. A. Elbadry
Affiliation:
Medical Parasitology Department, Faculty of Medicine, Cairo University, Cairo, Egypt
F. H. Shalan
Affiliation:
Medical Parasitology Department, Faculty of Medicine, Menoufia University, Menoufia, Egypt
A. F. Afifi
Affiliation:
Medical Parasitology Department, Faculty of Medicine, Menoufia University, Menoufia, Egypt
*
Author for correspondence: E. V. N. Beshay, E-mail: engyvictor@med.menofia.edu.eg
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Abstract

Neurotoxocariasis (NT) is a serious condition that has been linked to reduced cognitive function, behavioural alterations and neurodegenerative diseases. Unfortunately, the available drugs to treat toxocariasis are limited with unsatisfactory results, because of the initiation of treatment at late chronic stages after the occurrence of tissue damage and scars. Therefore, searching for a new therapy for this important disease is an urgent necessity. In this context, cytotherapy is a novel therapeutic approach for the treatment of many diseases and tissue damages through the introduction of new cells into the damaged sites. They exert therapeutic effects by their capability of renewal, differentiation into specialized cells, and being powerful immunomodulators. The most popular cell type utilized in cytotherapy is the mesenchymal stem cells (MSCs) type. In the current study, the efficacy of MSCs alone or combined with albendazole was evaluated against chronic brain insults induced by Toxocara canis infection in an experimental mouse model. Interestingly, MSCs combined with albendazole demonstrated a healing effect on brain inflammation, gliosis, apoptosis and significantly reduced brain damage biomarkers (S100B and GFAP) and T. canis DNA. Thus, MSCs would be protective against the development of subsequent neurodegenerative diseases with chronic NT.

Keywords

Albendazoleapoptosisbraincytotherapyglial fibrillary acidic protein (GFAP)gliosismesenchymal stem cellsneurotoxocariasisToxocara canis and transforming growth factor-β (TGF- β)
Type
Research Article
Information
Parasitology , Volume 147 , Issue 7 , June 2020 , pp. 799 - 809
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Copyright
Copyright © The Author(s) 2020. Published by Cambridge University Press

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References

Abo-Shehada, MN and Herbert, IV (1989) Variations in innate resistance to experimental Toxocara canis infection in two strains of mice. Veterinary Parasitology 33, 297–307.CrossRefGoogle ScholarPubMed
Borecka, A, Gawor, J, Niedworok, M and Sordyl, B (2008) Detection of Toxocara canis larvae by PCR in the liver of experimentally infected Mongolian gerbils (Meriones unguiculatus). Helminthologia 45, 147.CrossRefGoogle Scholar
Caplan, AI (2009) Why are MSCs therapeutic? New data: new insight. The Journal of Pathology 217, 318–324.CrossRefGoogle ScholarPubMed
Carleton, HM, Drury, RAB and Wallington, EA (1980) Carleton's Histological Techniques. Oxford, USA: Oxford University Press.Google Scholar
Cekanaviciute, E, Dietrich, HK, Axtell, RC, Williams, AM, Egusquiza, R, Wai, KM, Koshy, AA and Buckwalter, MS (2014) Astrocytic TGF-β signaling limits inflammation and reduces neuronal damage during central nervous system Toxoplasma infection. Journal of Immunology 193, 139–149.CrossRefGoogle ScholarPubMed
Chou, CM and Fan, CK (2018) Significant apoptosis rather autophagy predominates in astrocytes caused by Toxocara canis larval excretory-secretory antigens. Journal of Microbiology, Immunology, and Infection S1684-1182, 30223–30228.Google ScholarPubMed
De Becker, A, Van Hummelen, P, Bakkus, M, Broek, IV, De Wever, J, De Waele, M and Van Riet, I (2007) Migration of culture-expanded human mesenchymal stem cells through bone marrow endothelium is regulated by matrix metalloproteinase-2 and tissue inhibitor of metalloproteinase-3. Haematologica 92, 440–449.CrossRefGoogle ScholarPubMed
de Boysson, H, Silva, NM, Comoz, F, Boutemy, J and Bienvenu, B (2015) Vasculitis secondary to anti-C1q antibodies induced by Toxocariasis. Infection 43, 755–758.Google ScholarPubMed
de Sampaio, E, Spohr, TC, Martinez, R, da Silva, EF, Neto, VM and Gomes, FC (2002) Neuroglia interaction effects on GFAP gene: a novel role for transforming growth factor-β1. European Journal of Neuroscience 16, 2059–2069.CrossRefGoogle Scholar
Deshayes, S, Bonhomme, J and de La Blanchardière, A (2016) Neurotoxocariasis: a systematic literature review. Infection 44, 565–574.CrossRefGoogle ScholarPubMed
Doyle, KP, Cekanaviciute, E, Mamer, LE and Buckwalter, MS (2010) TGF-β signaling in the brain increases with aging and signals to astrocytes and innate immune cells in the weeks after stroke. Journal of Neuroinflammation 7, 62.CrossRefGoogle ScholarPubMed
Eid, MM, El-Kowrany, S, Othman, AA, El Gendy, DI and Saied, EM (2015) Immunopathological changes in the brain of immunosuppressed mice experimentally infected with Toxocara canis. Korean Journal of Parasitology 53, 51–58.CrossRefGoogle ScholarPubMed
Fan, CK, Lin, YH, Du, WY and Su, KE (2003) Infectivity and pathogenicity of 14-month-cultured embryonated eggs of Toxocara canis in mice. Veterinary Parasitology 113, 145–155.CrossRefGoogle ScholarPubMed
Fan, CK, Holland, CV, Loxton, K and Barghouth, U (2015) Cerebral toxocariasis: silent progression to neurodegenerative disorders? Clinical Microbiology Reviews 28, 663–686.CrossRefGoogle ScholarPubMed
Finsterer, J and Auer, H (2007) Neurotoxocarosis. Revista do Instituto de Medicina Tropical de São Paulo 49, 279–287.CrossRefGoogle ScholarPubMed
Frank, JA, Miller, BR, Arbab, AS, Zywicke, HA, Jordan, EK, Lewis, BK and Bulte, JW (2003) Clinically applicable labeling of mammalian and stem cells by combining superparamagnetic iron oxides and transfection agents. Radiology 228, 480–487.CrossRefGoogle ScholarPubMed
Hammam, OA, Elkhafif, N, Attia, YM, Mansour, MT, Elmazar, MM, Abdelsalam, RM, Kenawy, SA, Aiman, S and El-Khatib, AS (2016) Wharton's jelly-derived mesenchymal stem cells combined with praziquantel as a potential therapy for Schistosoma mansoni induced liver fibrosis. Scientific Reports 6, 21005.CrossRefGoogle ScholarPubMed
Hrckova, G and Velebny, S (2001) Treatment of Toxocara canis infections in mice with liposome-incorporated benzimidazole carbamates and immunomodulatory glucan. Journal of Helminthology 75, 141–146.Google Scholar
Jacobs, DE, Zhu, X, Gasser, RB and Chilton, NB (1997) PCR-based methods for identification of potentially zoonotic ascaridoid parasites of the dog, fox and cat. Acta Tropica 68, 191–200.CrossRefGoogle Scholar
Janecek, E, Beineke, A, Schnieder, T and Strube, C (2014) Neurotoxocarosis: marked preference of Toxocara canis for the cerebrum and T. cati for the cerebellum in the paratenic model host mouse. Parasites and Vectors 7, 194.CrossRefGoogle Scholar
Janecek, E, Waindok, P, Bankstahl, M and Strube, C (2017) Abnormal neurobehaviour and impaired memory function as a consequence of Toxocara canis- as well as Toxocara cati-induced neurotoxocarosis. PLOS Neglected Tropical Diseases 11, e0005594.Google ScholarPubMed
Jasmin Jelicks, LA, Koba, W, Tanowitz, HB, Mendez-Otero, R, de Carvalho, ACC and Spray, DC (2012) Mesenchymal bone marrow cell therapy in a mouse model of Chagas disease. Where do the cells go?. PLoS Neglected Tropical Diseases 6, e1971.CrossRefGoogle Scholar
Kayes, SG (1997) Human toxocariasis and the visceral larva migrans syndrome: correlative immunopathology. Chemical Immunology 66, 99–124.CrossRefGoogle ScholarPubMed
Kleindienst, A, Hesse, F, Bullock, MR and Buchfelder, M (2007) The neurotrophic protein S100B: value as a marker of brain damage and possible therapeutic implications. Progress in Brain Research 161, 317–325.CrossRefGoogle ScholarPubMed
Kraitchman, DL, Tatsumi, M, Gilson, WD, Ishimori, T, Kedziorek, D, Walczak, P and Young, RG (2005) Dynamic imaging of allogeneic mesenchymal stem cells trafficking to myocardial infarction. Circulation 112, 1451.CrossRefGoogle ScholarPubMed
Leu, S, Lin, YC, Yuen, CM, Yen, CH, Kao, YH, Sun, CK and Yip, HK (2010) Adipose-derived mesenchymal stem cells markedly attenuate brain infarct size and improve neurological function in rats. Journal of Translational Medicine 8, 63.CrossRefGoogle ScholarPubMed
Liao, CW, Fan, CK, Kao, TC, Ji, DD, Su, KE, Lin, YH and Cho, WL (2008) Brain injury-associated biomarkers of TGF-beta1, S100B, GFAP, NF-L, tTG, Abeta PP, and tau were concomitantly enhanced and the UPS was impaired during acute brain injury caused by Toxocara canis in mice. BMC Infectious Diseases 8, 84.CrossRefGoogle Scholar
Liberto, CM, Albrecht, PJ, Herx, LM, Yong, VW and Levison, SW (2004) Proregenerative properties of cytokine-activated astrocytes. Journal of Neurochemistry 89, 1092–1100.CrossRefGoogle Scholar
Lloyd, S (1998) Toxocarosis. In Palmer, SR, Soulsby, L and Simpson, DH (eds), Zoonoses: Biology, Clinical Practice, and Public Health Control. New York, USA: Oxford University Press, pp. 841–854.Google Scholar
Lodi, D, Iannitti, T and Palmieri, B (2011) Stem cells in clinical practice: applications and warnings. Journal of Experimental and Clinical Cancer Research 30, 9.CrossRefGoogle ScholarPubMed
Macambira, SG, Vasconcelos, JF, Costa, CR, Klein, W, Lima, RS, Guimarães, P and Soares, MB (2009) Granulocyte colony-stimulating factor treatment in chronic Chagas disease: preservation and improvement of cardiac structure and function. FASEB Journal 23, 3843–3850.CrossRefGoogle ScholarPubMed
Mengying, Z, Yiyue, X, Tong, P, Yue, H, Limpanont, Y, Ping, H, Okanurak, K, Yanqi, W, Dekumyoy, P, Hongli, Z, Watthanakulpanich, D, Zhongdao, W, Zhi, W and Zhiyue, L (2017) Apoptosis and necroptosis of mouse hippocampal and parenchymal astrocytes, microglia and neurons caused by Angiostrongylus cantonensis infection. Parasites and Vectors 10, 611.CrossRefGoogle ScholarPubMed
Meyer, K and Kaspar, BK (2017) Glia-neuron interactions in neurological diseases: testing non-cell autonomy in a dish. Brain Research 1656, 27e39.CrossRefGoogle ScholarPubMed
Moreira, GM, de Lima Telmo, P, Mendonça, M, Moreira, ÂN, McBride, AJA, Scaini, CJ and Conceição, FR (2014) Human toxocariasis: current advances in diagnostics, treatment, and interventions. Trends in Parasitology 30, 456–464.CrossRefGoogle ScholarPubMed
Nicoletti, A (2013) Toxocariasis. In Garcia, HH, Tanowitz, HB and Del Brutto, OH (eds), Hand Book of Clinical Neurology. Amsterdam, The Netherlands, Elsevier B.V., pp. 217–228.Google Scholar
Oryan, A, Sadjjadi, SM and Azizi, S (2010) Longevity of Toxocara cati larvae and pathology in tissues of experimentally infected chickens. Korean Journal of Parasitology 48, 79–80.CrossRefGoogle ScholarPubMed
Othman, AA (2012) Therapeutic battle against larval toxocariasis: are we still far behind? Acta Tropica 124, 171–178.Google ScholarPubMed
Othman, AA, Abdel-Aleem, GA, Saied, EM, Mayah, WW and Elatrash, AM (2010) Biochemical and immunopathological changes in experimental neurotoxocariosis. Molecular and Biochemical Parasitology 172, 1–8.CrossRefGoogle Scholar
Oujamaa, L, Sibon, I, Vital, A and Menegon, P (2003) Cerebral vasculitis secondary to Toxocara canis and Fasciola hepatica co-infestation. Revue Neurologique 159, 447–450.Google ScholarPubMed
Pawlowski, Z (2001) Toxocariasis in humans: clinical expression and treatment dilemma. Journal of Helminthology 75, 299–305.CrossRefGoogle ScholarPubMed
Piera-Velazquez, S, Mendoza, F and Jimenez, S (2016) Endothelial to mesenchymal transition (EndoMT) in the pathogenesis of human fibrotic diseases. Journal of Clinical Medicine 5, 45.CrossRefGoogle ScholarPubMed
Resende, MN, Gazzinelli-Guimarães, PH, Barbosa, FS, Oliveira, ML, Nogueira, DS and Gazzinelli-Guimarães, AC (2015) New insights into the immunopathology of early Toxocara canis infection in mice. Parasites and Vectors 8, 354.CrossRefGoogle ScholarPubMed
Röhl, C, Lucius, R and Sievers, J (2007) The effect of activated microglia on astrogliosis parameters in astrocyte cultures. Brain Research 1129, 43–52.CrossRefGoogle ScholarPubMed
Teixeira, FG, Carvalho, MM, Sousa, N and Salgado, AJ (2013) Mesenchymal stem cells secretome: a new paradigm for central nervous system regeneration? Cellular and Molecular Life Sciences 70, 3871–3882.CrossRefGoogle ScholarPubMed
Thakur, RS, Tousif, S, Awasthi, V, Sanyal, A, Atul, PK, Punia, P and Das, J (2013) Mesenchymal stem cells play an important role in host protective immune responses against malaria by modulating regulatory T cells. European Journal of Immunology 43, 2070–2077.CrossRefGoogle ScholarPubMed
Velebny, S, Tomasovicova, O, Hrckova, G and Dubinsky, P (1997) Toxocara canis in mice: are liposomes and immunomodulator able to enhance the larvicidal effect of the anthelmintic? Helminthologia 34, 147–153.Google Scholar
Walsh, MG and Haseeb, MA (2012) Reduced cognitive functions in children with toxocariasis in a nationally representative sample of the United States. International Journal for Parasitology 42, 1159–1163.CrossRefGoogle Scholar
Weger, M, Diotel, N, Dorsemans, AC, Dickmeis, T and Weger, BD (2017) Stem cells and the circadian clock. Developmental Biology 431, 111–123.CrossRefGoogle ScholarPubMed
Wei, X, Yang, X, Han, ZP, Qu, FF, Shao, L and Shi, YF (2013) Mesenchymal stem cells: a new trend for cell therapy. Acta Pharmacologica Sinica 34, 747.CrossRefGoogle ScholarPubMed
Weiss, ML and Troyer, DL (2006) Stem cells in the umbilical cord. Stem Cell Review 2, 155–162.CrossRefGoogle ScholarPubMed
Xu, HJ, Qian, H, Zhu, W, Zhang, X, Yan, YM, Zhang, LL, Mao, F, Wang, M, Xu, HT and Xu, WR (2012) Mesenchymal stem cells relieve fibrosis of Schistosoma japonicum-induced mouse liver injury. Experimental Biology and Medicine 237, 585–592.CrossRefGoogle ScholarPubMed
Yang, Z and Wang, KK (2015) Glial fibrillary acidic protein: from intermediate filament assembly and gliosis to neurobiomarker. Trends in Neurosciences 38, 364–374.CrossRefGoogle ScholarPubMed
Yarsan, E, Altinsaat, C, Aycicek, H, Sahindokuyucu, F and Kalkan, F (2003) Effects of albendazole treatment on haematological and biochemical parameters in healthy and Toxocara canis infected mice. Turkish Journal of Veterinary and Animal Sciences 27, 1057–1063.Google Scholar
Young, C, Roth, KA, Klocke, BJ, West, T, Holtzman, DM, Labruyere, J, Qin, YQ, Dikranian, K and Olney, JW (2005) Role of caspase-3 in ethanol-induced developmental neurodegeneration. Neurobiology of Disease 20, 608–614.CrossRefGoogle ScholarPubMed
Zhang, Y, Jing, YM, Rui, YJ, Xu, YL and Wang, W (2014) Stem cell therapy for the treatment of parasitic infections: is it far away? Parasitology Research 113, 607–612.CrossRefGoogle ScholarPubMed
Zhu, H, Guo, ZK, Jiang, XX, Li, H, Wang, XY, Yao, HY and Mao, N (2010) A protocol for isolation and culture of mesenchymal stem cells from mouse compact bone. Nature Protocols 5, 550–560.CrossRefGoogle ScholarPubMed