Retrospective study of mesenchymal stem cell therapy in dogs with neurological complications resulting from infection by canine distemper virus
DOI:
https://doi.org/10.14295/bjs.v1i11.191Keywords:
ambulatory difficulties, epileptic crises, myoclonus, remyelination, safetyAbstract
Canine distemper virus causes death in a large proportion of infected dogs. For the survivors, various physiological systems can be damaged, including the nervous system, resulting in neurological signs such as ataxia, paresis or plegias, myoclonus, tremors and epileptic crises. Mesenchymal stem cells are undifferentiated cells with the capacity to release trophic factors with neuroprotective, anti-inflammatory and immunomodulatory properties, and as such may represent an alternative to treat or mitigate the clinical symptoms in dogs with such neurological sequelae. In the current retrospective study, we evaluated clinical data and films from 14 dogs that presented myoclonus, epileptic episodes, and/or ambulatory difficulties after distemper virus infection, and that were treated with allogeneic mesenchymal stem cells from a cell bank. The animals that had presented epileptic crises and myoclonus presented a reduction in the frequency of these episodes, and of the 14 animals that presented with ambulatory difficulties, ten regained the ability to walk without aid after the therapy. No animal presented with any adverse reaction to the cell transplant. These results suggest that mesenchymal stem cell therapy may be an alternative for treatment of neurological sequelae, however, further controlled studies should be carried out in order to obtain further data regarding the number of cells to be transplanted, the time interval between transplants, and even about the ideal time for initiation of such therapy.
References
Araújo, J. D., Araújo Filho, J. D., Ciorlin, E., Ruiz, M. A., Ruiz, L. P., Greco, O. T., Lago, M. R., Ardito, R. V. (2005). A terapia celular no tratamento da isquemia crítica dos membros inferiores. Journal Vascular Brazil, 4(4), 357-365. DOI: https://doi.org/10.1590/S1677-54492005000400011
Bianco, P., Riminucci, M., Gronthos, S., Robey, P. G. (2001). Bone marrow stromal stem cell: nature, biology and potential applications. Stem Cell, 19, 180-191. DOI: https://doi.org/10.1634/stemcells.19-3-180
Bittencourt, R. A. C., Pereira, H. R., Felisbino, S. L., Murador, P., Oliveira, A. P. E., Deffune, E. (2006). Isolamento de células-tronco mesenquimais da medula óssea. Acta Ortopédica Brasileira, 14(1), 22-34. DOI: https://doi.org/10.1590/S1413-78522006000100004
Brito, H. F. V., Corat, M. A. F., Santos, M. R., Gilioli, R., Passos, L. A. C., Lancelloti, M., Ferreira, F., Min L. L. (2010). Tratamento de sequelas neurológicas em cães, causadas por infecção pelo vírus da cinomose, através do transplante alogênico de células mononucleares de medula óssea. Medvep - Revista Científica de Medicina Veterinária - Pequenos Animais e Animais de Estimação, 8(24), 26-29.
Caplan A. I. (2009). Why are MSCs therapeutic? New data: new insight. Journal of Pathology, 217, 318-324, 2009. DOI: https://doi.org/10.1002/path.2469
Chung, D. J., Hayashi, K., Toupadakis, C. A., Clare, A. W., Yellowley, E. (2012). Osteogenic proliferation and differentiation of canine bone marrow and adipose tissue derived mesenchymal stromal cells and the influence of hypoxia. Research in Veterinary Science, 92, 66-75. DOI: https://doi.org/10.1016/j.rvsc.2010.10.012
Colomé, M., Gomes, C., Crosignani, N., Paz, A. H., Lugo, A. A., Guimarães, K. M., Foerstrow, L. P. Tessari, J. P., Colomé, L. M., Graça, D. L., Meurer, L., Passos, E. P., Pippi, N. L., Contesini, E. A., Lima, E. O. C. (2008). Utilização de células-tronco autólogas de medula óssea na regeneração do nervo tibial de coelhos mediante técnica de tubulização com prótese de silicone. Ciência Rural, 38(9), 2529-2534. DOI: https://doi.org/10.1590/S0103-84782008000900018
Costa B. G. (2012). Utilização de terapia celular em afecções neurológicas do sistema nervoso central. Monografia (Graduação) – Curso de Medicina Veterinária da Universidade Federal do Rio Grande do Sul – UFRGS. Porto Alegre – RS.
Dos Santos, B. P. C. R. (2013). Efeito da acupuntura no tratamento de animais com sequelas neurológicas decorrentes de cinomose. Dissertação De Mestrado, Unesp – Botucatu.
Escalhão, C. C. M., Ramos, I. P. R., Hochman-Mendez, C., Brunswick, T. H. K., Souza, S. A. L., Gutfilen, B., Goldenberg, R. C. S., Coelho-Sampaio, T. (2017). Safety of Allogeneic Canine Adipose Tissue-Derived Mesenchymal Stem Cell Intraspinal Transplantation in Dogs with Chronic Spinal Cord Injury. Stem Cells International, 2017, 3053759. https://doi.org/10.1155/2017/3053759 DOI: https://doi.org/10.1155/2017/3053759
Gade, N. E., Pratheesh, M. D., Nath, A., Dubey, P. K., Sharma, A. G. T. (2012). Therapeutic potential of stem cells in veterinary practice. Veterinary World, 5(8), 499-507. DOI: https://doi.org/10.5455/vetworld.2012.499-507
Gazit, Z., Pelled, G., Sheyn, D., Kimelman, N., Gazit, D. (2011). Mesenchymal Stem Cells: Principles of Regenerative Medicine (Second edition), 17, 285-304. DOI: https://doi.org/10.1016/B978-0-12-381422-7.10017-3
Greene C. E., Appel M. J. (2006). Canine distemper. In: Greene C.E. (Org.) Infectious diseases of the dog and cat. 3ª ed, St. Louis: Saunders Elsevier, 3, 25-41.
Gugliandolo A., Bramanti, P., Mazzon, E. (2017). Mesenchymal stem cell therapy in Parkinson’s disease animal models. Curr Res Transl Med., 65(2), 51-60. https://doi.org/10.1016/j.retram.2016.10.007 DOI: https://doi.org/10.1016/j.retram.2016.10.007
Girdlestone J. (2016). Mesenchymal stromal cells with enhanced therapeutic properties. Immunotherapy, 8(12), 1405–1416. DOI: https://doi.org/10.2217/imt-2016-0098
Huang, C., Kristen, L. H., Frost, L. E., Sun, Y., Cheung, H. S. (2004). Effects of cyclic compressive loading on chondrogenesis of rabbit bone-marrow derived mesenchymal stem cells. Stem Cells, 22, 313-23. DOI: https://doi.org/10.1634/stemcells.22-3-313
Jung, D. I., Ha, J., Kang, B. T., Kim, J. W., Quan, F. S., Lee, J. H., Woo, E. J., Park, H. M. (2009). A comparison of autologous and allogenic bone marrow-derived mesenchymal stem cell transplantation in canine spinal cord injury. Journal of the Neurological Sciences, 285, 67–77. DOI: https://doi.org/10.1016/j.jns.2009.05.027
Kang, S. K., Shin, M. J., Jung, J. S., Kim, Y. G., Kim, C. H. (2006). Autologous adipose tissue-derived stromal cells for treatment of spinal cord injury. Stem Cells Dev., 15(4), 583-594. DOI: https://doi.org/10.1089/scd.2006.15.583
Kern, S., Eichler, H., Stoeve, J., Klüter, H., Bieback, K. (2006). Comparative analysis of mesenchymal stem cells from bone marrow, umbilical cord blood, or adipose tissue. Stem Cells, 24, 1294-1301. DOI: https://doi.org/10.1634/stemcells.2005-0342
Kim, H., Kim, H. Y., Choi, M. R., Hwang, S., Nam, K. H., Kim, H. C., et al. (2010). Dose-dependent efficacy of ALS-human mesenchymal stem cells transplantation into cisterna magna in SOD1-G93A ALS mice. Neurosci Lett., 468(3), 190–194. DOI: https://doi.org/10.1016/j.neulet.2009.10.074
Kim, Y., Lee, S. H., Kim, W. H., Kweon O. K. (2016). Transplantation of adipose derived mesenchymal stem cells for acute thoracolumbar disc disease with no deep pain perception in dogs. J Vet Sci, 17(1), 123-126. DOI: https://doi.org/10.4142/jvs.2016.17.1.123
Krakowa, S., Axthelm, M. K., Johnson, G. C. (1985). Canine distemper virus. In: Olsen R.G., Krakowa S., Blakeslee J.R. Comparative pathobiology of viral diseases. Boca Raton: CRC, 8, 137-164. DOI: https://doi.org/10.1201/9780429286643-8
Karumbayaram, S., Novitch, B. G., Patterson, M., Umbach, J. A., Richter, L., Lindgren, A., et al. (2009). Directed differentiation of human-induced pluripotent stem cells generates active motor neurons. Stem Cells, 27(4), 806–811. DOI: https://doi.org/10.1002/stem.31
Le Blanc, K., Tammika, C., Rosendahl, K., Zetterberg, E., Ringde´n, O. (2003). HLA expression and immunologic properties of differentiated and undifferentiated mesenchymal stem cells. Experimental Hematology, 31, 890–896. DOI: https://doi.org/10.1016/S0301-472X(03)00110-3
Marconi, S., Bonaconsa, M., Scambi, I., Squintani, G. M., Rui, W., Turano, E, et al. (2013). Systemic treatment with adipose-derived mesenchymal stem cells ameliorates clinical and pathological features in the amyotrophic lateral sclerosis murine model. Neuroscience, 248:333–343 DOI: https://doi.org/10.1016/j.neuroscience.2013.05.034
Marques, A. R. P. A. (2016). Terapia com células estaminais derivadas do tecido adiposo em cães com sequelas neurológicas da esgana. Universidade Lusófona de Humanidades e Tecnologias. Dissertação de Mestrado. Faculdade de Medicina Veterinária, Lisboa.
Martinello, T., Bronzini, I., Maccatrozzo, L., Mollo, A., Sampaolesi, M., Mascarello, F., Decaminada, M. (2011). Canine adipose-derived-mesenchymal stem cells do not lose stem features after a long-term cryopreservation. Research in Veterinary Science, 91, 18-24. DOI: https://doi.org/10.1016/j.rvsc.2010.07.024
Mao, Z., Zhang, S., Chen, H. (2015). Stem cell therapy for amyotrophic lateral sclerosis. Cell Regeneration, 4(11). https://doi.org/10.1186/s13619-015-0026-7. DOI: https://doi.org/10.1186/s13619-015-0026-7
Monteiro, B. S., Argolo Neto, N. M., Del Carlo, R. J. (2010). Células-tronco mesenquimais. Ciência Rural, 40(1). DOI: https://doi.org/10.1590/S0103-84782010000100040
Moro, L., Alves, C. M., Santos, F. G. A., Martins, A. S., Vasconcelos, A. C. (2003). Apoptose na desmielinização da cinomose canina (Revisão de literatura). Bioscience J., 20(2), 171-178.
Mota, A. C. A., Soares, M. B. P., Santos R. R. (2005). Uso de terapia regenerativa com células-tronco da medula óssea em doenças cardiovasculares – perspectivas do hematologista. Revista Brasileira Hematologia e Hemoterapia, 27, 126-132. DOI: https://doi.org/10.1590/S1516-84842005000200013
Nakage, A. P. M., Santana, A. E. (2006). Células-tronco hematopoiéticas em cães. Ciência Rural, 36(1), 325-329. DOI: https://doi.org/10.1590/S0103-84782006000100054
Oliveira, C. D., Vieira, S., Souza, F. S. L., Oliveira, F. T., Mattos, V. Z., Marins, A. L. C, Moura, S. M. Stem cell therapy for cardiology: a new path to humanity and a new care for nurses - a case report. Online Brazilian Journal of Nursing, 4(1), 2005. DOI: https://doi.org/10.17665/1676-4285.20054783
Pinheiro, A. O. (2014). Avaliação do tratamento experimental de cães infectados naturalmente pelo vírus da cinomose canina na fase neurológica com o uso de células-tronco de epitélio olfatório fetal canino. Dissertação apresentada ao Programa de Pós-Graduação em Anatomia dos Animais Domésticos e Silvestres da Faculdade de Medicina Veterinária e Zootecnia da Universidade de São Paulo.
Quimby, J. M., Webb, T. L., Habenicht, L. M., Dow, S. W. (2013). Safety and efficacy of intravenous infusion of allogeneic cryopreserved mesenchymal stem cells for treatment of chronic kidney disease in cats: results of three sequential pilot studies. Stem Cell Research & Therapy, 4(2), 48. https://doi.org/10.1186/scrt198. DOI: https://doi.org/10.1186/scrt198
Rivera, F. J., Kandasamy, M., Cpuillard-despres, M., Caioni, M., Sanchez, R., Huber, C. (2008). Oligodendrogenesis of adult neural progenitors: differential effects of ciliary neurotrophic factor and mesenchymal stem cell derived factors. J Neurochem, 107, 832-843. DOI: https://doi.org/10.1111/j.1471-4159.2008.05674.x
Rodrigues, C. C. B.; Zappa, V. (2009). Cinomose e o processo de desmielinização. Revista científica eletrônica de medicina veterinári, 7(12).
Secco, M. (2011). Avaliação do potencial terapêutico de células-tronco Mesenquimais do cordão umbilical humano associadas ao IGF-1 para distrofias musculares progressivas. Instituto de Biociências da Universidade de São Paulo, SP, Tese de Doutorado.
Tipold A., Vandevelde M., Jaggy A. (1992). Neurological manifestations of canine distemper virus infection. Journal of Small Animal Practice, 33, 466-470. DOI: https://doi.org/10.1111/j.1748-5827.1992.tb01024.x
Vandevelde M., Zurbriggen A. (2005). Demyelination in canine distemper virus infection: a review. Acta Neuropathologica, 109(1), 56-68. DOI: https://doi.org/10.1007/s00401-004-0958-4
Zamprogno, H. (2007). Células-tronco esqueléticas para o tratamento da união de fraturas. Acta Scientiae Veterinariae, 35(2), 289-290.
Zhang, J., Li, Y., Chen, J., Cui, Y., Lu, M., Elias, S. B. (2005) Human bone marrow stromal cell treatment improves neuroglical functional recovery in EAE mice. Exp Neurol, 195, 16-26. DOI: https://doi.org/10.1016/j.expneurol.2005.03.018
Zhao, J., Shi, N., Sun, Y., Martella, V., Nikolin, V., Zhu, C., Zhang, H., Hu, B., Bai, X., Yan, X. (2015). Pathogenesis of canine distemper virus in experimentally infected raccoon dogs, foxes, and minks. Antiviral Research, 122, 1–11. DOI: https://doi.org/10.1016/j.antiviral.2015.07.007
Downloads
Published
How to Cite
Issue
Section
License
Copyright (c) 2022 Hilana dos Santos Sena Brunel, Carla Lujan Villaroel, Bruno Stéfano Lima Dallago, Robert Pogue, Patrícia Furtado Malard
This work is licensed under a Creative Commons Attribution 4.0 International License.
Authors who publish with this journal agree to the following terms:
1) Authors retain copyright and grant the journal right of first publication with the work simultaneously licensed under a Creative Commons Attribution License that allows others to share the work with an acknowledgement of the work's authorship and initial publication in this journal.
2) Authors are able to enter into separate, additional contractual arrangements for the non-exclusive distribution of the journal's published version of the work (e.g., post it to an institutional repository or publish it in a book), with an acknowledgement of its initial publication in this journal.
3) Authors are permitted and encouraged to post their work online (e.g., in institutional repositories or on their website) prior to and during the submission process, as it can lead to productive exchanges, as well as earlier and greater citation of published work.
