Contamination of Mesenchymal Stem-Cells with Fibroblasts Accelerates Neurodegeneration in an Experimental Model of Parkinson's Disease

Contamination of Mesenchymal Stem-Cells with Fibroblasts Accelerates Neurodegeneration in an Experimental Model of Parkinson's Disease

Author Pereira, Márcia Cristina Leite Autor UNIFESP Google Scholar
Secco, Mariane Google Scholar
Suzuki, Daniela Emi Autor UNIFESP Google Scholar
Janjoppi, Luciana Autor UNIFESP Google Scholar
Rodini, Carolina Oliveira Autor UNIFESP Google Scholar
Torres, Laila Brito Autor UNIFESP Google Scholar
Araujo, Bruno Henrique Silva Autor UNIFESP Google Scholar
Cavalheiro, Esper Abrão Autor UNIFESP Google Scholar
Zatz, Mayana Google Scholar
Okamoto, Oswaldo Keith Autor UNIFESP Google Scholar
Institution Universidade Federal de São Paulo (UNIFESP)
Universidade de São Paulo (USP)
Abstract Pre-clinical studies have supported the use of mesenchymal stem cells (MSC) to treat highly prevalent neurodegenerative diseases such as Parkinson's disease (PD) but preliminary trials have reported controversial results. in a rat model of PD induced by MPTP neurotoxin, we first observed a significant bilateral preservation of dopaminergic neurons in the substantia nigra and prevention of motor deficits typically observed in PD such as hypokinesia, catalepsy, and bradykinesia, following intracerebral administration of human umbilical cord-derived MSC (UC-MSC) early after MPTP injury. However, surprisingly, administration of fibroblasts, mesenchymal cells without stem cell properties, as a xenotransplantation control was highly detrimental, causing significant neurodegeneration and motor dysfunction independently of MPTP. This observation prompted us to further investigate the consequences of transplanting a MSC preparation contaminated with fibroblasts, a plausible circumstance in cell therapy since both cell types display similar immunophenotype and can be manipulated in vitro under the same conditions. Here we show for the first time, using the same experimental model and protocol, that transplantation of UC-MSC induced potent neuroprotection in the brain resulting in clinical benefit. However, co-transplantation of UC-MSC with fibroblasts reverted therapeutic efficacy and caused opposite damaging effects, significantly exacerbating neurodegeneration and motor deficits in MPTP-exposed rats. Besides providing a rationale for testing UC-MSC transplantation in early phases of PD aiming at delaying disease progression, our pre-clinical study suggests that fibroblasts may be common cell contaminants affecting purity of MSC preparations and clinical outcome in stem cell therapy protocols, which might also explain discrepant clinical results.
Keywords Mesenchymal stem cells
Umbilical cord
Parkinson's disease
Cell therapy
Language English
Sponsor Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)
Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)
INCT Celulas-tronco em Doencas Gencticas Humanas
Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)
Date 2011-11-01
Published in Stem Cell Reviews and Reports. Totowa: Humana Press Inc, v. 7, n. 4, p. 1006-1017, 2011.
ISSN 1550-8943 (Sherpa/Romeo, impact factor)
Publisher Humana Press Inc
Extent 1006-1017
Access rights Open access Open Access
Type Article
Web of Science ID WOS:000297597800022

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