Title
Survival, differentiation, and neuroprotective mechanisms of human stem cells complexed with neurotrophin-3-releasing pharmacologically active microcarriers in an ex vivo model of parkinson’s disease
Date Issued
01 January 2015
Access level
open access
Resource Type
journal article
Author(s)
Daviaud N.
Garbayo E.
Sindji L.
MartÍnez-Serrano A.
Montero-Menei C.N.
University of Miami Miller
Publisher(s)
AlphaMed Press
Abstract
Stem cell-based regenerative therapies hold great potential for the treatment of degenerative disorders such as Parkinson’s disease (PD). We recently reported the repair and functional recovery after treatment with human marrow-isolated adult multilineage inducible (MIAMI) cells adhered to neurotrophin-3 (NT3) releasing pharmacologically active microcarriers (PAMs) in hemiparkinsonian rats. In order to comprehend this effect, the goal of the present work was to elucidate the survival, differentiation, and neuroprotective mechanisms of MIAMI cells and human neural stem cells (NSCs), both adhering to NT3-releasing PAMs in an ex vivo organotypic model of nigrostriatal degeneration made from brain sagittal slices. It was shown that PAMs led to a marked increase in MIAMI cell survival and neuronal differentiation when releasing NT3. A significant neuroprotective effect of MIAMI cells adhering to PAMs was also demonstrated. NSCs barely had a neuroprotective effect and differentiated mostly into dopaminergic neuronal cells when adhering to PAM-NT3. Moreover, those cells were able to release dopamine in a sufficient amount to induce a return to baseline levels. Reverse transcription-quantitative polymerase chain reaction and enzyme-linked immunosorbent assay analyses identified vascular endothelial growth factor (VEGF) and stanniocalcin-1 as potential mediators of the neuroprotective effect of MIAMI cells and NSCs, respectively. It was also shown that VEGF locally stimulated tissue vascularization, which might improve graft survival, without excluding a direct neuroprotective effect of VEGF on dopaminergic neurons. These results indicate a prospective interest of human NSC/PAM and MIAMI cell/PAM complexes in tissue engineering for PD.
Start page
670
End page
684
Volume
4
Issue
6
Language
English
OCDE Knowledge area
Biología celular, Microbiología Neurociencias
Scopus EID
2-s2.0-84930526205
PubMed ID
Source
Stem Cells Translational Medicine
ISSN of the container
21576564
Sponsor(s)
U.S. Department of Veterans Affairs I01BX000952 VA
Sources of information: Directorio de Producción Científica Scopus