2026-04-14T19:32:49Zhttps://uvadoc.uva.es/oai/request

oai:uvadoc.uva.es:10324/714592024-12-11T10:20:16Zcom_10324_1138com_10324_931com_10324_894col_10324_1226

Alonso-Alonso, Maria L. Srivastava, Girish Kumar Usategui Martín, Ricardo García Gutiérrez, María Teresa Pastor Jimeno, José Carlos Fernández Bueno, Iván 2024-11-14T11:45:50Z 2024-11-14T11:45:50Z 2020 Stem Cells International 2020;9463548 1687-966X https://uvadoc.uva.es/handle/10324/71459 10.1155/2020/9463548 1 14 Stem Cells International 2020 1687-9678 Producción Científica Mesenchymal stem cells (MSC) secrete neuroprotective molecules that may be useful as an alternative to cell transplantation itself. Our purpose was to develop different pharmaceutical compositions based on conditioned medium (CM) of adipose MSC (aMSC) stimulated by and/or combined with nicotinamide (NIC), vasoactive intestinal peptide (VIP), or both factors; and to evaluate in vitro their proliferative and neuroprotective potential. Nine pharmaceutical compositions were developed from 3 experimental approaches: (1) unstimulated aMSC-CM collected and combined with NIC, VIP, or both factors (NIC+VIP), referred to as the aMSC-CM combined composition; (2) aMSC-CM collected just after stimulation with the mentioned factors and containing them, referred to as the aMSC-CM stimulated-combined composition; and (3) aMSC-CM previously stimulated with the factors, referred to as the aMSC stimulated composition. The potential of the pharmaceutical compositions to increase cell proliferation under oxidative stress and neuroprotection were evaluated in vitro by using a subacute oxidative stress model of retinal pigment epithelium cells (line ARPE-19) and spontaneous degenerative neuroretina model. Results showed that oxidatively stressed ARPE-19 cells exposed to aMSC-CM stimulated and stimulated-combined with NIC or NIC+VIP tended to have better recovery from the oxidative stress status. Neuroretinal explants cultured with aMSC-CM stimulated-combined with NIC+VIP had better preservation of the neuroretinal morphology, mainly photoreceptors, and a lower degree of glial cell activation. In conclusion, aMSC-CM stimulated-combined with NIC+VIP contributed to improving the proliferative and neuroprotective properties of the aMSC secretome. Further studies are necessary to evaluate higher concentrations of the drugs and to characterize specifically the aMSC-secreted factors related to neuroprotection. However, this study supports the possibility of improving the potential of new effective pharmaceutical compositions based on the secretome of MSC plus exogenous factors or drugs without the need to inject cells into the eye, which can be very useful in retinal pathologies. Fondo Europeo de Desarrollo Regional and Consejería de Educación [grant number VA077P17] and the Centro en Red de Medicina Regenerativa y Terapia Celular Grants, both Junta de Castilla y León, Spain application/pdf eng info:eu-repo/semantics/openAccess http://creativecommons.org/licenses/by-nc-nd/3.0/ Attribution-NonCommercial-NoDerivs 3.0 Unported Mesenchymal Stem Cell Secretome Enhancement by Nicotinamide and Vasoactive Intestinal Peptide: A New Therapeutic Approach for Retinal Degenerative Diseases info:eu-repo/semantics/article info:eu-repo/semantics/publishedVersion SI