Centro Andaluz de Biología Molecular y Medicina Regenerativa
Vivian Capilla González

Email: vivian.capilla@cabimer.es

SCIENTIFIC PROGRAM: CELL-BASED THERAPIES TO IMPROVE CANCER TREATMENTS

Main Research Lines:

  1. Development of stem cell-based therapies to reduce side effects of oncologic treatments in preclinical models.
  2. Prevention of neurological sequelae in the treatment of pediatric cancer (+VIDA Project).
  3. Novel strategies to improve therapeutic potential of mesenchymal stem cells in cancer.

Cancer burden raised to 18.1 million new cases and 9.6 million cancer deaths in 2018. However, the number of people that survive cancer is increasing due to advances in early detection and treatments for cancer. For this reason, more attention is being paid to the impact of cancer treatments on patients’ health and quality of life. Radiotherapy is one of the most common treatments for cancer. Around 50% of all tumor patients receive radiation at a given time. Unfortunately, radiotherapy comes with short and long term side effects. In particular, radiation for brain tumors produces neurofunctional sequelae, which may be progressive and permanent. The most frequently described neurological alterations of cranial radiation include learning and memory difficulties, problems in executive functions, reduced processing speed, attention deficits, visual alterations and intellectual decline among others. These neurological sequelae are particularly relevant for pediatric patients because their developing brains are more radiosensitive. Therefore, there is an urgent need to develop new strategies to prevent radiation side effects and promote a healthy cancer-free life.

The use of advanced therapy medicinal products (ATMPs), including stem cells, has emerged as a promising alternative in regenerative medicine. Our group brings over 15 years of experience in stem cell research. Our scientific program aims to investigates stem cell-based strategies to improve cancer treatments from two complementary perspectives; reducing sequelae of cancer treatments and developing new cancer therapeutics. The ultimate goal of our research is to improve the quality of life of cancer patients.

Prevention of the sequelae of cancer treatments. We have demonstrated that mesenchymal stem cells (MSCs) exhibit neuroprotective effects in a preclinical mouse model of cranial radiotherapy. In particular, we work with the intranasal via as a non-invasive method to deliver cells into the brain, which represents an interesting option for clinical application. We are evaluating the efficacy and safety of MSC transplantation for minimizing radiation-related damages, including cognitive deficits. We also explore the mechanisms involved in the neuroprotective effects of MSCs against neurological complications of radiotherapy. This line of research encompasses the +VIDA project, which gives special attention to pediatric cancer survivors (https://www.precipita.es/precipitado/prevencion-de-las-complicaciones-neurologicas-del-tratamiento-del-cancer-infantil.html).

Development of new cancer therapeutics. A growing body of research has used MSC-based strategies for cancer treatment. However, the therapeutic potential of MSCs in cancer is still controversial. While some studies indicate that MSCs may contribute to cancer pathogenesis, emerging data reported the suppressive effects of MSCs on cancer cells. Our objective is to understand when MSCs promote or suppress tumor development with the ultimate goal of design MSC-based therapy for cancer.

Principal investigator:

Instituto de Salud Carlos III. Ayuda vinculada al Contrato Miguel Servet (CP19/00046). Development of cell-based strategies to prevent sequelae of cancer treatment.

Precipita-FECYT-MCIU (2018-000237). Proyecto +VIDA: Prevención de las Complicaciones Neurológicas del Tratamiento del Cáncer Infantil.

Consejería de Salud de la Junta de Andalucía (PI-0272-2017). Prevención de Los Daños Por Radioterapia Mediante Aplicación de Terapia Celular: Una Estrategia Anti-Inflamatoria.

Fundación Publica Andaluza Progreso y Salud – Junta de Andalucía (PI-0109-2014). Implicaciones de la radiación en la capacidad regenerativa endógena del cerebro.

Investigator:

NOMA (No-MOre-Amputations) (PIC18/00010). Instituto de Salud Carlos III. Proyectos de investigación en Terapias Avanzadas.

RED TEMÁTICA DE INVESTIGACIÓN COOPERATIVA EN SALUD, CONVOCATORIA 2016, PROGRAMA RETICS-RED DE TERAPIA CELULAR (RD16/0011/0034). Instituto de Salud Carlos III.

Preparación de un medicamento celular basado en la obtención de células productoras de insulina diferenciadas procedentes de células pluripotentes humanas. Instituto de Salud Carlos III. Proyectos de investigación en salud.

RED TEMÁTICA DE INVESTIGACIÓN COOPERATIVA EN SALUD, CONVOCATORIA 2012, PROGRAMA RETICS-RED DE TERAPIA CELULAR (RD12/0019/0028). Instituto de Salud Carlos III.

RED TEMÁTICA DE INVESTIGACIÓN COOPERATIVA EN SALUD, CONVOCATORIA 2012, PROGRAMA RETICS-RED DE TERAPIA CELULAR (RD12/0019/0028). Instituto de Salud Carlos III.

Centro de Investigacion Biomedica en Enfermedades Neurodegenerativas (CIBERNED) CB06/05/1131 Instituto de Salud Carlos III.

RED TEMÁTICA DE INVESTIGACIÓN COOPERATIVA EN SALUD CONVOCATORIA 2006, PROGRAMA RETICS-RED DE TERAPIA CELULAR TERCEL. (RD06/0010/0022) Instituto de Salud Carlos III.

Bernat Soria, Alejandro Martin-Montalvo, Yolanda Aguilera, Nuria Mellado-Damas, Javier Lopez-Beas, Isabel Herrera-Herrera, Maria Escarlata Lopez, Juan A. Barcia, Manuel Alvarez Dolado, Abdelkrim Hmadcha and Vivian Capilla-González. Human Mesenchymal Stem Cells Prevent Neurological Complications of Radiotherapy. Front Cell Neurosci 2019

Livia López-Noriega L, Vivian Capilla-González, Nadia Cobo-Vuilleumier, Martin-Vazquez E, Lorenzo PI, Martinez-Force E, Soriano-Navarro M, García-Fernández M, Romero-Zerbo SY, Bermúdez-Silva FJ, Díaz-Contreras I, Sánchez-Cuesta A, Santos-Ocaña C, Hmadcha A, Soria B, Martín F, Gauthier BR, Martin-Montalvo AInadequate control of thyroid hormones sensitizes to hepatocarcinogenesis and unhealthy aging. Aging 2019

Natalia Escacena-Acosta, Javier Lopez-Beas, Christian Claude Lachaud, Mehrdad Vakilian, Juan Rigoberto Tejedo, Vivian Capilla-González, Francisco Javier Bedoya, Franz Martin, Abdelkrim Hmadcha, Bernat Soria. Stem Cells: Concept, Properties, and Characterization. Corneal Regeneration: Therapy and Surgery. Springer 2019.

Bárbara Soria-Juan* Natalia Escacena* Vivian Capilla-González*, Yolanda Aguilera; Lucia Llanos, Juan Tejedo, Francisco Bedoya, Verónica Juan, Antonio de la Cuesta, Rafael Ruiz-Salmeron, Enrique Andreu, Lukas Grochowicz, Felipe Prosper, Fermin Sanchez-Guijo, Francisco Lozano, Manuel Miralles, Lourdes del Rio-Sola, Gregorio Castellanos, Jose Maria Moraleda, Robert Sakstein, Mariano Garcia-Arranz, Damian Garcia-Olmo, Franz Martin, Abdelkrim Hmadcha, Bernat Soria. Cost-Effective, Safe and Personalized Cell Therapy of Critical Limb Ischemia in Type 2 Diabetes Mellitus. Frontiers in Immunology 2019

Vivian Capilla-González; Javier López-Beas; Natalia Escacena; Yolanda Aguilera; Antonio de la Cuesta; Vivian Capilla-Gonzalez; Franz Martín; Abdelkrim Hmadcha; Bernat Soria. PDGF restores the defective phenotype of adipose-derived mesenchymal stromal cells from diabetic patients. Molecular Therapy 2018

Javier López-Beas*; Vivian Capilla-González*; Yolanda Aguilera; Nuria Mellado; Christian C. Lachaud; Franz Martín; Vivian Capilla-Gonzalez; Bernat Soria; Abdelkrim Hmadcha. miR-7 modulates human embryonic stem cell differentiation into insulin-producing beta-like cells and contributes to cell maturation. Molecular Therapy – Nucleic Acids 2018.

Mendivil-Perez, M; Soto-Mercado, V; Fernandez-Gil, B; Guerra Librero, A; Florido, J; Shen, YQ; Vivian Capilla-Gonzalez; Tejada, M; Garcia-Verdugo, JM; Acuña-Castroviejo, D; Carlos-López, C; Velez-Pardo, C; Jimenez-Del-Rio, M; Rusanova, I; Escames, G. Melatonin enhances neural stem cell differentiation and engraftment by increasing mitochondrial function. Journal of Pineal Research. 2017

Hugo Guerrero-Cázares; Emily Lavey; Linda Chen; Paula Schiapparelli; Montserrat Lara-Velazquez; Vivian Capilla-Gonzalez; Gabrielle Drummond; Anna Clements; Liron Noiman; Katrina Thaler; Anne Burke; Alfredo Quiñones-Hinojosa. Robo1 regulates the migration of human subventricular zone neural progenitor cells during development. Stem Cells 2017

Angela Fontan Lozano; Vivian Capilla Gonzalez; Yolanda Aguilera; Nuria Mellado; Angel Carrion; Bernat Soria; Abdelkrim Hmadcha. Impact of transient downregulation of DREAM in human embryonic stem cell pluripotency. Stem Cell Research 2016

Vivian Capilla Gonzalez; Janice M Bonsu; Kristin J Redmond; Jose Manuel Garcia Verdugo; Alfredo Quiñones Hinojosa 2016. Implications of Irradiating the Subventricular Zone Stem Cell Niche. Stem Cell Research 2016

Kalyan Kondapalli; Jose Llongueras; Vivian Capilla-Gonzalez; Hari Prasad; Anniesha Hack; Christopher Smith; Hugo Guerrero-Cázares; Alfredo Quiñones-Hinojosa; Rajini Rao. A leak pathway for luminal protons in endosomes drives oncogenic signaling in glioblastoma. Nature Communications 2015

Natalia Escacena; Elena Quesada Hernández; Vivian Capilla Gonzalez; Bernat Soria; Abdelkrim Hmadcha. Bottlenecks in the efficient use of advanced therapy medicinal product based on mesenchymal stromal cells. Stem cells international 2015

Vivian Capilla Gonzalez; Emily Lavell; Alfredo Quiñones Hinojosa; Hugo Guerrero Cazares. Regulation of Subventricular Zone-Derived Cells Migration in the Adult Brain. Adv Exp Med Biol. 2015

Xavier d’Anglemont de Tassigny; M Salomé Sirerol Piquer; Ulises Gómez Pinedo; Ricardo Pardal; Sonia Bonilla; Vivian Capilla González; Javier de la Torre; José Manuel García Verdugo; José López Barneo. Resistance of subventricular neural stem cells to chronic hypoxemia with structural disorganization of the germinal center and impairment of neuronal and oligodendrocyte survival. Hypoxia 2015

Vivian Capilla-Gonzalez; Vicente Herranz-Perez; Jose Manuel Garcia-Verdugo. The aged brain: genesis and fate of residual progenitor cells in the subventricular zone. Frontiers in cellular neuroscience 2015

Vivian Capilla Gonzalez; Arantxa Cebrian Silla; Hugo Guerrero Cazares; Jose Manuel Garcia Verdugo; Alfredo Quiñones Hinojosa. Age-related changes in astrocytic and ependymal cells of the subventricular zone. Glia 2014

Vivian Capilla Gonzalez; Hugo Guerrero Cazares; Janice M Bonsu; Oscar Gonzalez Perez; Pragathi Achanta; John Wong; Jose Manuel Garcia Verdugo; Alfredo Quiñones Hinojosa. The subventricular zone is able to respond to a demyelinating lesion after localized radiation. Stem Cells 2014

Vivian Capilla Gonzalez; Arantxa Cebrian Silla; Hugo Guerrero Cazares; Jose M Garcia Verdugo; Alfredo Quiñones Hinojosa. The generation of oligodendroglial cells is preserved in the rostral migratory stream during aging. Frontiers in cellular neuroscience 2013

Rodrigo Ramos Zúñiga; Oscar González Pérez; Ana Macías Ornelas; Vivian Capilla González; Alfredo Quiñones Hinojosa. Ethical implications in the use of embryonic and adult neural stem cells. Stem cells international 2012

Vivian Capilla Gonzalez; Sara Gil Perotin; Antonio Ferragud; Luis Bonet Ponce; Juan Jose Canales; Jose Manuel Garcia Verdugo. Exposure to N-ethyl-N-nitrosourea in adult mice alters structural and functional integrity of neurogenic sites. PloS One 2012.

Pragathi Achanta; Vivian Capilla Gonzalez; David Purger; Juvenal Reyes; Kurt Sailor; Hongjun Song; Jose Manuel Garcia Verdugo; Oscar Gonzalez Perez; Eric Ford; Alfredo Quinones Hinojosa. Subventricular zone localized irradiation affects the generation of proliferating neural precursor cells and the migration of neuroblasts. Stem Cells 2012

Vivian Capilla-Gonzalez; Vicente Hernandez-Rabaza. Cocaine and MDMA Induce Cellular and Molecular Changes in Adult Neurogenic Systems: Functional Implications. Pharmaceuticals 2011

Vivian Capilla Gonzalez; Sara Gil Perotin; Jose Manuel Garcia Verdugo. Postnatal exposure to N-ethyl-N-nitrosurea disrupts the subventricular zone in adult rodents. European journal of neuroscience 2010

Kaisorn L Chaichana; Hugo Guerrero Cazares; Vivian Capilla Gonzalez; Grettel Zamora Berridi; Pragathi Achanta; Oscar Gonzalez Perez; George I Jallo; Jose Manuel Garcia Verdugo; Alfredo Quiñones Hinojosa. Intra-operatively obtained human tissue: protocols and techniques for the study of neural stem cells. Journal of neuroscience methods 2009

María Del Carmen Gómez Roldán; Margarita Pérez Martín; Vivian Capilla González; Manuel Cifuentes; Juan Pérez; Jose Manuel García Verdugo; Pedro Fernández Llebrez. Neuroblast proliferation on the surface of the adult rat striatal wall after focal ependymal loss by intracerebroventricular injection of neuraminidase. Journal of comparative neurology 2008

Kaisorn L Chaichana; Vivian Capilla Gonzalez; Oscar Gonzalez Perez; Gustavo Pradilla; James Han; Alessandro Olivi; Henry Brem; Jose Manuel Garcia Verdugo; Alfredo Quiñones Hinojosa. Preservation of glial cytoarchitecture from ex vivo human tumor and non-tumor cerebral cortical explants: A human model to study neurological diseases. Journal of neuroscience methods 2007

Maria Duran Moreno; Vivian Capilla Gonzalez; Jose Manuel Garcia Verdugo. Neurogénesis en la zona subventricular Tumores intraventriculares. Permanyer 2010

Susana Gonzalez Granero; Clara Alfaro Cervello; Vivian Capilla Gonzalez; Melissa Lezameta Morgan; Miriam Romaguera Ros; Jose Manuel Garcia Verdugo. Neurogenic sites in non-mammalian vertebrales Postnatal and adult neurogenesis. Research Signpost. 2008.

Susana Gonzalez Granero; Vivian Capilla Gonzalez; Melissa Lezameta Morgan; Jose Manuel Garcia Verdugo. Aspectos comparados de la neurogenesis y migración tangencial al Bulbo Olfatorio La olfacción en España. SBI, S.L. 2006.