RT Journal Article
T1 Generation of periventricular reactive astrocytes overexpressing aquaporin 4 Is stimulated by mesenchymal stem cell therapy
A1 García-Bonilla, María
A1 Ojeda-Pérez, Betsaida
A1 Shumilov, Kirill
A1 Rodríguez-Pérez, Luis Manuel
A1 Domínguez-Pinos, Dolores
A1 Vitorica Ferrández, Javier
A1 Jiménez, Sebastián
A1 Ramírez-Lorca, Reposo
A1 Echevarría, Miriam
A1 Cárdenas García, Casimiro
A1 Iglesias, Teresa
A1 Gutiérrez-Pérez, Antonia
A1 McAllister, James P. (II)
A1 Limbrick, David D. (Jr.)
A1 Páez-González, Patricia
A1 Jiménez-Lara, Antonio Jesús
K1 Hidrocefalia -- Tratamiento
K1 Células madre -- Uso terapéutico
K1 Terapia celular
K1 Medicina regenerativa
K1 Experimentación animal
AB Aquaporin-4 (AQP4) plays a crucial role in brain water circulation and is considered a therapeutic target in hydrocephalus. Congenital hydrocephalus is associated with a reaction of astrocytes in the periventricular white matter both in experimental models and human cases. A previous report showed that bone marrow-derived mesenchymal stem cells (BM-MSCs) transplanted into the lateral ventricles of hyh mice exhibiting severe congenital hydrocephalus are attracted by the periventricular astrocyte reaction, and the cerebral tissue displays recovery. The present investigation aimed to test the effect of BM-MSC treatment on astrocyte reaction formation. BM-MSCs were injected into the lateral ventricles of four-day-old hyh mice, and the periventricular reaction was detected two weeks later. A protein expression analysis of the cerebral tissue differentiated the BM-MSC-treated mice from the controls and revealed effects on neural development. In in vivo and in vitro experiments, BM-MSCs stimulated the generation of periventricular reactive astrocytes overexpressing AQP4 and its regulatory protein kinase D-interacting substrate of 220 kDa (Kidins220). In the cerebral tissue, mRNA overexpression of nerve growth factor (NGF), vascular endothelial growth factor (VEGF), hypoxia-inducible factor-1 (HIF1α), and transforming growth factor beta 1 (TGFβ1) could be related to the regulation of the astrocyte reaction and AQP4 expression. In conclusion, BM-MSC treatment in hydrocephalus can stimulate a key developmental process such as the periventricular astrocyte reaction, where AQP4 overexpression could be implicated in tissue recovery.
PB MDPI
YR 2023
FD 2023-03-15
LK https://hdl.handle.net/10630/26802
UL https://hdl.handle.net/10630/26802
LA eng
NO García-Bonilla M, Ojeda-Pérez B, Shumilov K, Rodríguez-Pérez L-M, Domínguez-Pinos D, Vitorica J, Jiménez S, Ramírez-Lorca R, Echevarría M, Cárdenas-García C, Iglesias T, Gutiérrez A, McAllister JP II, Limbrick DD Jr., Páez-González P, Jiménez AJ. Generation of Periventricular Reactive Astrocytes Overexpressing Aquaporin 4 Is Stimulated by Mesenchymal Stem Cell Therapy. International Journal of Molecular Sciences. 2023; 24(6):5640. https://doi.org/10.3390/ijms24065640
NO The present work was supported by grants PI15/00619 and PI19/00778 (to A.J.J. and P.P.-G.), PI21/000914 (to J.V.) and PI21/000915 (to A.G.) from the Instituto de Salud Carlos III, Spain, co-financed by FEDER funds from the European Union; PI18-RT-2233 from Junta de Andalucía (to A.G.) co-financed by Programa Operativo FEDER 2014–2020; PID2020-115218RB-I00 to T.I., funded by MCIN/AEI/10.13039/501100011033; Centro de Investigación Biomédica en Red de Enfermedades Neurodegenerativas (CIBERNED, Instituto de Salud Carlos III, Spain) to J.V., T.I. and A.G.; FPU13/02906 to MG-B from the Ministerio de Educación, Cultura y Deporte, Spain; RYC-2014-16980 to P.P.-G. from the Ministerio de Economía y Competitividad, Spain; UMA18-FEDERJA-277 from Plan Operativo FEDER Andalucía 2014–2020 and Universidad de Málaga to P.P.-G.; Proyectos dirigidos por jóvenes investigadores from Universidad de Málaga to P.P.-G. The cost of this publication has been paid in  art by “ERDF A way of making Europe” funds. Partial funding for open access charge: Universidad de Málaga.
DS RIUMA. Repositorio Institucional de la Universidad de Málaga
RD 21 ene 2026