C.I. Fernández, L. Castillo, I. Horruitiner, A. Toledano, M.A. León Díaz del Guante, M.E. González, L. Hidalgo

Background. Current evidence suggests that bone marrow stem cells (BMSC) contribute to lesioned/degenerated brain tissue repair by both secretion of trophic paracrine factors and functional incorporation into affected regions. Hypothesis. In vitro generated conditioned medium from cultured BMSC (CM-BMSC) replaces the stem cell grafting benefits in early Alzheimer’s and Parkinson’s diseases models respectively. Methods. BMSC-derived conditioned medium (BMSC-CM) was obtained from culture expanded BMSC (10 passages). BMSC cellular suspensions were processed to allow fluorescent detection after grafting. Classical stains and BrU labeling/ counting cells were used to determine neurogenic activity. Other immunohistochemical markers were used to evaluated neural phenotype. Motor, sensorimotor and learning/memory functions were evaluated through a multiple behavioral battery. Neurochemical studies (aminoacid levels –AAs- and glutathione content –GSH- determinations) were carried out before/after or after treatment, respectively (time treatment: 12/24 weeks). Results. All treated subjects improved their initial motor or cognitive impairment as well as compared to respective controls. Nevertheless, the most significant long term behavioral recovery was detected in BMSC-CM rats. Similarly, in this group GSH and AAs levels exhibit a marked and favourable modifications comparing with those rats from other groups. Furthermore, IVI of BMSC-CM stimulated proliferation/migration events at the subventricular zone (SVZ) or dentate gyrus (DG)differentially in each model. Conclusions: Results suggests that paracrine signals from stem and progenitor cells are decisive players in the cell-mediated restorative therapy. Their acting as a “signals whole integrator” relying on neurogenesis stimulation; through neuromodulatory and neuroprotective influences in the target brain, inducing a significant/sustained behavioral recovery. Considering the technical, ethical and practical limitations of cell therapy, cell free conditioned media could be a potent alternative for therapeutic neurogenesis in neurodegenerative diseases

Keywords (Optional): 
animal model
neurodegenerative disease
stem cells
mild cognitive impairment
preclinical parkinsonism