Grafted Neural Precursors Integrate Into Mouse Striatum, Differentiate and Promote Recovery of Function Through Release of Erythropoietin in MPTP-Treated Mice

Stephana Carelli, Toniella Giallongo, Cristina Viaggi, Zuzana Gombalova, Elisa Latorre, Massimiliano Mazza, Francesca Vaglini, Anna Maria Di Giulio, Alfredo Gorio

Research output: Contribution to journalArticle

Abstract

Erythropoietin-releasing neural precursor cells (Er-NPCs) are a subclass of subventricular zone-derived neural progenitors, capable of surviving for 6 hr after death of donor. They present higher neural differentiation. Here, Er-NPCs were studied in animal model of Parkinson's disease. Dopaminergic degeneration was caused by 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine intraperitoneal administration in C57BL/6 mice. The loss of function was evaluated by specific behavioral tests. Er-NPCs (2.5 × 10(5)) expressing the green fluorescent protein were administered by stereotaxic injection unilaterally in the left striatum. At the end of observational research period (2 weeks), most of the transplanted Er-NPCs were located in the striatum, while several had migrated ventrally and caudally from the injection site, up to ipsilateral and contralateral substantia nigra. Most of transplanted cells had differentiated into dopaminergic, cholinergic, or GABAergic neurons. Er-NPCs administration also promoted a rapid functional improvement that was already evident at the third day after cells administration. This was accompanied by enhanced survival of nigral neurons. These effects were likely promoted by Er-NPCs-released erythropoietin (EPO), since the injection of Er-NPCs in association with anti-EPO or anti-EPOR antibodies had completely neutralized the recovery of function. In addition, intrastriatal administration of recombinant EPO mimics the effects of Er-NPCs. We suggest that Er-NPCs, and cells with similar properties, may represent good candidates for cellular therapy in neurodegenerative disorders of this kind.

Original languageEnglish
JournalASN Neuro
Volume8
Issue number5
DOIs
Publication statusPublished - Oct 2016

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1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine
Recovery of Function
Erythropoietin
Substantia Nigra
Injections
GABAergic Neurons
Cholinergic Neurons
Lateral Ventricles
Dopaminergic Neurons
Green Fluorescent Proteins
Inbred C57BL Mouse
Neurodegenerative Diseases
Parkinson Disease
Anti-Idiotypic Antibodies
Animal Models

Keywords

  • Journal Article

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Grafted Neural Precursors Integrate Into Mouse Striatum, Differentiate and Promote Recovery of Function Through Release of Erythropoietin in MPTP-Treated Mice. / Carelli, Stephana; Giallongo, Toniella; Viaggi, Cristina; Gombalova, Zuzana; Latorre, Elisa; Mazza, Massimiliano; Vaglini, Francesca; Di Giulio, Anna Maria; Gorio, Alfredo.

In: ASN Neuro, Vol. 8, No. 5, 10.2016.

Research output: Contribution to journalArticle

Carelli, Stephana ; Giallongo, Toniella ; Viaggi, Cristina ; Gombalova, Zuzana ; Latorre, Elisa ; Mazza, Massimiliano ; Vaglini, Francesca ; Di Giulio, Anna Maria ; Gorio, Alfredo. / Grafted Neural Precursors Integrate Into Mouse Striatum, Differentiate and Promote Recovery of Function Through Release of Erythropoietin in MPTP-Treated Mice. In: ASN Neuro. 2016 ; Vol. 8, No. 5.
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AU - Latorre, Elisa

AU - Mazza, Massimiliano

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AU - Di Giulio, Anna Maria

AU - Gorio, Alfredo

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