Abba, Martín
Centro de Investigaciones Inmunológicas Básicas y Aplicadas (CINIBA), Facultad de Medicina, UNLP.
García, Mariana
Hospital Austral, Universidad Austral, Pilar. Provincia de Buenos Aires.
Lacunza, Ezequiel
Facultad de Ciencias Médicas, UNLP.
Mazzolini, Guillermo
Hospital Austral, Universidad Austral, Pilar. Provincia de Buenos Aires.
Las therapeutic potential of mesenchymal stem cells (MSCs) in the senile brain
Mesenchymal cells (MSCs), also known as mesenchymal stromal cells or multipotent stromal cells, can be described as progenitors of similar-fibroblast morphology that are obtained when adherent-to-plastic cells are cultured from diverse tissues. There is a growing interest in the therapeutic, anti-inflammatory and regenerative capacity of MSCs. In the last years numerous experimental studies were published which describe the application of MSCs in animal models of myocardial infarction, hepatic fibrosis, and neurodegeneration. In this last field, the experimental application of MSCs is focused on models of Alzheimer's disease (AD) and Parkinson's disease (PD). In this way it was documented that the injection of umbilical cord-derived MSCs, in a murine model of AD, is capable of reducing the expression of markers for glial activation, oxidative stress, and apoptosis. The therapeutic potential of MSCs was also examined in animal models of PD, evaluating the intrinsic neurorestoration capacity of MSCs and their utility as source of dopaminergic (DA) neurons. In this last aspect, it was documented that bone marrow MSCs can be differentiated to functionally active DA neurons when cultured in a medium containing fibroblast factor growth 2 (FGF2) as sole inducer.
Messenchymal stem cells as vehicles of therapeutic genes
The low immunogenicity of MSCs converts them into promising candidates for its use as vehicles of therapeutic genes, having already published numerous preclinical studies that show the benefits of the application of MSCs transduced with therapeutic genes in animal models of clinical interest. In a recent study, Fiore and collaborators used adenovectors built in our laboratory that express insulin-like growth factor-I (IGF-I) or green fluorescent protein (GFP) to transducer MSCs from human bone marrow successfully used in a murine model of liver fibrosis. Our group demonstrated that intracerebroventricular (ICV) with IGF-I gene therapy restores partial but significantly the motor performance in senile female rats. More recently we demonstrated that ICV for IGF-I gene therapy in senile rats attenuates its deficit in spatial memory and some of the morphological alterations in the hippocampus. For that purpose, MSCs transduced with viral vectors expressing IGF-I result of significant interest for the implementation of gene and cell therapy in the senile CNS.
The objective of the present line is to use adult stem cells (MSCs), naïve or transduced with adenovectors that express the gen for the insulin-like growth factor-I (IGF-I), to implement gene and cell therapy in the senile rat brain.
Mesenchymal stem cell therapy improves spatial memory and hippocampal structure in aging rats.
Zappa Villar, Maria F.; Lehmann, Marianne; García, Mariana G.; Mazzolini, Guillermo; Morel, Gustavo R.; Cónsole, Gloria M.; Podhajcer, Osvaldo; Reggiani, Paula C.; Goya, Rodolfo G.
2019: Behavioural brain research. Amsterdam: ELSEVIER SCIENCE BV, p. 1-5. ISSN 0166-4328
doi.org/10.1016/j.bbr.2019.04.001
IGF-I gene therapy as a potentially useful therapy for spontaneous prolactinomas in senile rats.
Brown, O. A; Canatelli-Mallat, M; Cónsole, G. M; Camihort, G; Luna, G; Spinedi, E; Goya, R. G.
2018. Current gene therapy. BENTHAM SCIENCE PUBL LTD, vol. 18, n° 4, p. 240-245. ISSN 1566-5232
Identification of a conserved gene signature associated with an exacerbated inflammatory environment in the hippocampus of aging rats.
Pardo, J; Abba, M. C; Lacunza, E; Francelle, L; Morel, G. R; Outeiro, T. F; Goya, R. G.
2017. Hippocampus. Apr;27(4):435-449. Doi: 10.1002/hipo.22703
Epub 2017 Jan 23. PubMed PMID: 28085212
Therapeutic potential IGF-I on hippocampal neurogenesis and function during aging.
Morel, G. R; Lopez-León, M; Uriarte Donati, M; Reggiani, P. C; Goya, R. G.
2017. Neurogenesis, Austin (Texas): London: Taylor & Francis Group, LLC, vol. 4, n° 1, ISSN 2326-2133
A rat treated with mesenchymal stem cells livesto 44 months of age.
Mansilla. E; Roque. G; Sosa. Y. E; Tarditti, A; Goya, R. G.
2016. Rejuvenation Research. New York: MARY ANN LIEBERT INC, vol. 19, n° 4, p. 318-321. ISSN 1549-1684
Insulin-like growth factor-I gene therapy increases hippocampal neurogenesis, astrocyte branching and improves spatial memory in female aging rats.
Pardo, J; Uriarte, M; Cónsole, G. M; Reggiani, P; Outeiro, T. F; Morel, G. R; Goya, R. G.
2016. Eur J Neurosci. Aug;44(4):2120-8. Doi: 10.1111/ejn.13278
Epub 2016 Jun 8. PubMed PMID: 27188415
Cognitive impairment and morphological changes in the dorsal hippocampus of very old female rats.
Morel, G; Andersen, T; Pardo, J; Zucolilli, G. O; Cambiaggi, V. L; Hereñú, C; Goya, R. G.
2015. Neuroscience. Amsterdam: PERGAMON-ELSEVIER SCIENCE LTD, p. 189-199. ISSN 0306-4522
Neuroprotective gene therapy in the aging brain.
Pardo, J; Morel, G. R; Pereyra, A. S; López-León, M; Brown-O. A, Bellini, M. J; Goya, R. G.
2014. Estrogens and Cognition. Psycho-biological and Clinical Aspects: González-Burgos (Ed.) ISBN: 978-81-308-0550-4; pp.97-117
Hypothalamic insulin-like growth factor-I gene therapy prolongs estral cyclicity and protects ovarian structure in middle-aged female rats.
Rodriguez, S. S; Schwerdt, J. I; Barbeito, C. G; Flamini, A. M; Han, Y; Bohn, M. C; Goya, R. G.
2013. Endocrinology.Bethesda: Endocrine Soc. vol. 154, n° 6, p. 2166-2173. ISSN 0013-7227
Increased number of neurons in the cervical spinal cord of aged female rats.
Portiansky, E. L; Nishida, F; Barbeito, C. G; Gimeno, E. J; Goya, R. G.
2011. PloS One, 6: e22537
Insulin-like growth factor I gene delivery to astrocytes reduces their inflammatory response to lipopolysaccharide.
Bellini, M. J; Hereñú, C. B; Goya, R. G; García Segura, L. M.
2011. Neuroinflammation, 8: 21
Restorative effect of intracerebroventricular Insulin-like Growth Factor-I gene therapy on motor performance in aging rats.
Nishida, F; Morel, G. R; Hereñú, C. B; Schwerdt, J. I; Goya, R. G; Portiansky, E. L.
2011. Neuroscience, 177: 195 - 206
Long-term deficiency of circulating and hippocampal insulin-like growth factor I induces depressive behavior; adult mice: a potential model of geriatric depression.
Mitschelen, M; Yan, H; Farley, J. A; Warrington, J. P; Han, S; Hereñú, C. B; Csiszar, A; Ungvari, Z; Bailey-Downs, L. C; Bass, C. E; Sonntag, W. E.
2011. Neuroscience; 185: 50 - 60
Morphological changes induced by insulin-like growth factor-I gene therapy in pituitary cell populations in experimental prolactinomas.
Camihort, G. A; Hereñú, C. B; Luna, G. C; Rodríguez, S. S; Bracamonte, M. I; Goya, R. G; Cónsole, G. M.
2010. Cells tissues organs. Karger. vol. 191, p. 316-325
Glial cell line-derived neurotrophic factor gene therapy ameliorates chronic hyperprolactinemia in senile rats.
Morel, G. R; Sosa, Y. E; Bellini, M. J; Carri, N. G; Rodriguez, S, S; Bohn, M. C; Goya, R.
2010. Neuroscience; vol. 167 p. 946 - 953
The ependymal route for insulin-like growth factor-1 gene therapy in the brain.
Hereñu C. B; Sonntag W.E; Morel G. R; Portiansky E. L; Goya R. G.
2009. Neuroscience. Elsevier, vol. 163, p. 442-447
Insulin-like growth factor-I gene therapy reverses morphologic changes and reduces hyperprolactinemia in experimental rat prolactinomas.
Console, G. M; Hereñu, C. B; Camihort, G. A; Luna, G. C; Bracamonte, M. I; Morel, G. R; Goya, R. G.
2008. Molecular cancer. Londres: Blackwell Scientific Publications, p. 7-13
Dopaminergic mesencephalic systems and motor performance in very old rats.
Sánchez, H. L; Silva, L. B; Portiansky, E. L; Hereñu, C. B; Goya, R. G.
2008. Neuroscience. USA: Elsevier, vol. 154, n° 4, p. 1598-1606
Restorative effect of Insulin-like Growth Factor-I Gene Therapy in the Hypothalamus ofsenile rats with Dopaminergic dysfunction.
Hereñu, C. B; Cristina, C; Rimoldi, O. J; Becu-Villalobos, S; Cambiaggi, V; Portiansky, E. L; Goya, R. G.
2007. Gene therapy. Nature Publishing Group. vol. 14, p. 237-245. ISSN 0969-7128
Logros y promesas de la medicina regenerativa en el tratamiento de enfermedades neurodegenerativas.
López-León, M; Lehmann, M; Goya, R. G.
2016. Universidad de Murcia (Master); 6º Ed.; Viguera Editores SLU; Barcelona; 2016. Capítulo en el libro “Desordenes del Movimientro”.
Medicina regenerativa para el tratamiento de enfermedades nuerodegenerativas.
López-León, M: Goya, R. G.
2015. Universidad de Murcia (Master); 5º Ed.; Viguera Editores SLU; Barcelona. Capítulo en el libro “Desordenes del Movimientro”
Gene Delivery Systems.
Pereyra, A. S; Hereñu, C. B.; Romanovsky, V; Zgela, V; Bakic, S.
2013. Editorial InTech, p. 165-192. ISBN 978-953-51-1207-5
Neuroendocrine system and aging: growth hormone, thyroid stimulating hormone, prolactin and insulin.
Sonntag William, E; Hereñú, C. B; Goya, R. G.
2008. New York. New Encyclopedia of Neuroscience
Neuroendocrine Aging: Pituitary-metabolism.
Sonntag W. E; Hereñú, C. B.
2006. New Encyclopedia of Neuroscience; p. 1-18
Premio al mejor trabajo en investigación básica en el 2º Congreso Internacional de la Facultad de Cs Médicas de la UNLP.
Trabajo: Pardo, J; Abba, M; Lacunza, E; Schwerdt, J; Cónsole, G; Outeiro, T; Morel, G; Goya, R. “Expresión génica diferencial de hipocampo en un modelo de envejecimiento cerebral tratado con terapia génica de largo plazo”. Presentación oral. Noviembre 2015.
Distinción otorgada al trabajo científico: “Transferencia génica asistida por campos magnéticos: estudios en células gliales”. Pardo, J; Sosa, Y. E; Reggiani, P. C; Arciniegas, M. L; Sánchez, F; Goya, R. G.
ActaBioqClinLatinoam. 47 (2): 399-406 (2013) por parte de la Asociación de Prensa Científica de la República Argentina, para su publicación en un número especial, dedicado a la difusión de los diez trabajos científicos argentinos más destacados del año 2014, de edición binacional portugués-español del Acta Bioquímica Clínica Latinoamericana.
“Profesor Dr. Samuel M. Mc Cann 2007”
Otorgado por la Sociedad Argentina de Fisiología en el marco de la Reunión 2007, realizada conjuntamente con las Sociedades Argentinas de Investigación clínica e Inmunología. Mar del Plata, 24 de noviembre de 2007.
Otorgado según el dictamen del jurado, al mejor trabajo sobre Neuroinmunoendocri- nología, titulado: Terapia génica neonatal para el péptido tímico timulina como estrategia preventiva de las alteraciones ováricas en el ratón congenitamenteatímico.
Reggiani, P. C; Barbeito, C. G; Flamini, M. A; Cónsole , G.M; Rodríguez, S. S, Dardenne, M; Goya, R. G.
“Profesor Doctor Manuel Litter”
Otorgado por la Asociación Médica Argentina y la Sociedad Argentina de Farmacología y Terapéutica. Buenos Aires, 5 de noviembre de 2007.
Al mejor trabajo científico titulado: Restauración de de la función reproductiva en ratones inmunodeficientes por medio de terapia génica con el gen del péptido timulina.
Reggiani, P. C; Martínez, E.V; Camihort, G. A; Luna, G. C; Brown, O. A; Goya, R. G; Cónsole, G. M.
“2000 Eukanuba Prize”
Al mejor trabajo argentino sobre medicina veterinaria, presentado en "The North American Veterinary Conference". January 13 al 17, 2001, Orlando, USA.
Título: Growth hormone reference range and stimulation tests in intact dogs.
Corrada, Y. A; Goya, R. G; Gobello, M. C.
“Premio Sandoz”
Al mejor poster presentado en el 186th Meeting of the Society for Endocrinology, Londres, 22 - 23 noviembre de 1995. Conjuntamente recibido con Castro, M. G; Lowenstein, P. R; Sosa, Y. E.
“Premio bienal FABA 1993”
Otorgado por la Federación Bioquímica de la Provincia de Buenos Aires.
Trabajo: "Hormonas tímicas como mediadoras de la integración inmuno-gonadotropa". Brown, O. A; Sosa, Y, E; Goya, R. G.
Invitado por la Fundación SANDOZ para Investigaciones Gerontológicas, para participar, como representante único de la región latinoamericana, en el Simposio Internacional "Mechanisms of Homeostasis in Aging", llevado a cabo en Basilea, Suiza, en marzo de 1992
2º Premio Latinoamericano de Gerontología
Otorgado por la Federación Latinoamericana de Gerontología y Geriatría a los 3 mejores trabajos científicos presentados durante el 6º Congreso Latinoamericano de Gerontologia y Geriatría celebrado en Buenos Aires- 2 al 7 de octubre de 1988.
Título: "Cambios en los perfiles secretorios de somatotrofina y tirotrofina durante el envejecimiento en la rata".
Medalla y diploma otorgados por el Colegio de Bioquímicos de la Provincia de Buenos Aires al mejor egresado de la promoción 1982 en la Facultad de Ciencias Exactas de la Universidad Nacional de La Plata.
