Dose-dependent effect of mesenchymal stromal cells co-grafted with dopaminergic neurons in a Parkinson's disease rat model
Rodriguez-Pallares, Jannette ; Garcia-Garrote, Maria LU
; Parga, Juan A.
and Labandeira-Garcia, Jose Luis
(2021)
In Journal of Cellular and Molecular Medicine
25(20).
p.9884-9889
- Abstract
A major limiting factor for cell therapy in Parkinson's disease is the poor survival and reinnervation capacity of grafted dopaminergic neurons, independently of the cell source. Mesenchymal stromal cells (MSCs) have high capability to regulate the local environment through the release of trophic, antiapoptotic and immunomodulatory factors. In this work, we investigated whether co-grafting of MSCs could improve the survival and reinnervation ability of dopaminergic precursors transplanted in animal models of Parkinson's disease. Rats with total unilateral dopaminergic denervation were grafted with a cell suspension of rat dopaminergic precursors (500,000 cells) with or without a high (200,000 cells) or low (25,000 cells) number of MSCs.... (More)
A major limiting factor for cell therapy in Parkinson's disease is the poor survival and reinnervation capacity of grafted dopaminergic neurons, independently of the cell source. Mesenchymal stromal cells (MSCs) have high capability to regulate the local environment through the release of trophic, antiapoptotic and immunomodulatory factors. In this work, we investigated whether co-grafting of MSCs could improve the survival and reinnervation ability of dopaminergic precursors transplanted in animal models of Parkinson's disease. Rats with total unilateral dopaminergic denervation were grafted with a cell suspension of rat dopaminergic precursors (500,000 cells) with or without a high (200,000 cells) or low (25,000 cells) number of MSCs. Eight weeks after grafting, rats were tested for motor behaviour and sacrificed for histological analysis. Our results showed that the survival of dopaminergic neurons and graft-derived striatal dopaminergic innervation was higher in rats that received co-grafts containing a low number of MSCs than in non-co-grafted controls. However, the survival of dopaminergic neurons and graft-derived dopaminergic reinnervation was lower in rats receiving co-grafts with high number of MSCs than in non-co-grafted controls. In conclusion, co-grafting with MSCs or MSCs-derived products may constitute a useful strategy to improve dopaminergic graft survival and function. However, a tight control of MSCs density or levels of MSCs-derived products is necessary.
(Less)
- author
- Rodriguez-Pallares, Jannette
; Garcia-Garrote, Maria
LU
; Parga, Juan A.
and Labandeira-Garcia, Jose Luis
- publishing date
- 2021-10
- type
- Contribution to journal
- publication status
- published
- keywords
- cell death, cell therapy, dopaminergic neuron, Parkinson, stem cells, transplantation
- in
- Journal of Cellular and Molecular Medicine
- volume
- 25
- issue
- 20
- pages
- 6 pages
- publisher
- Wiley-Blackwell
- external identifiers
-
- scopus:85115029492
- pmid:34535974
- ISSN
- 1582-1838
- DOI
- 10.1111/jcmm.16900
- language
- English
- LU publication?
- no
- additional info
- Publisher Copyright: © 2021 The Authors. Journal of Cellular and Molecular Medicine published by Foundation for Cellular and Molecular Medicine and John Wiley & Sons Ltd.
- id
- aea72928-fc31-46c1-8feb-96996c639add
- date added to LUP
- 2025-01-24 11:53:45
- date last changed
- 2025-01-30 12:37:01
@article{aea72928-fc31-46c1-8feb-96996c639add,
abstract = {{<p>A major limiting factor for cell therapy in Parkinson's disease is the poor survival and reinnervation capacity of grafted dopaminergic neurons, independently of the cell source. Mesenchymal stromal cells (MSCs) have high capability to regulate the local environment through the release of trophic, antiapoptotic and immunomodulatory factors. In this work, we investigated whether co-grafting of MSCs could improve the survival and reinnervation ability of dopaminergic precursors transplanted in animal models of Parkinson's disease. Rats with total unilateral dopaminergic denervation were grafted with a cell suspension of rat dopaminergic precursors (500,000 cells) with or without a high (200,000 cells) or low (25,000 cells) number of MSCs. Eight weeks after grafting, rats were tested for motor behaviour and sacrificed for histological analysis. Our results showed that the survival of dopaminergic neurons and graft-derived striatal dopaminergic innervation was higher in rats that received co-grafts containing a low number of MSCs than in non-co-grafted controls. However, the survival of dopaminergic neurons and graft-derived dopaminergic reinnervation was lower in rats receiving co-grafts with high number of MSCs than in non-co-grafted controls. In conclusion, co-grafting with MSCs or MSCs-derived products may constitute a useful strategy to improve dopaminergic graft survival and function. However, a tight control of MSCs density or levels of MSCs-derived products is necessary.</p>}},
author = {{Rodriguez-Pallares, Jannette and Garcia-Garrote, Maria and Parga, Juan A. and Labandeira-Garcia, Jose Luis}},
issn = {{1582-1838}},
keywords = {{cell death; cell therapy; dopaminergic neuron; Parkinson; stem cells; transplantation}},
language = {{eng}},
number = {{20}},
pages = {{9884--9889}},
publisher = {{Wiley-Blackwell}},
series = {{Journal of Cellular and Molecular Medicine}},
title = {{Dose-dependent effect of mesenchymal stromal cells co-grafted with dopaminergic neurons in a Parkinson's disease rat model}},
url = {{http://dx.doi.org/10.1111/jcmm.16900}},
doi = {{10.1111/jcmm.16900}},
volume = {{25}},
year = {{2021}},
}