title: Grafted Neural Precursors Integrate Into Mouse Striatum, Differentiate and Promote Recovery of Function Through Release of Erythropoietin in MPTP-Treated Mice.
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 × 105) 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.
authors: Laboratories of Pharmacology, Department of Health Sciences, University of Milan, Italy stephana.carelli@guest.unimi.it.
authors: Stephana
authors: S
authors: Carelli
authors: Laboratories of Pharmacology, Department of Health Sciences, University of Milan, Italy.
authors: Toniella
authors: T
authors: Giallongo
authors: Dipartimento di Ricerca Traslazionale e delle Nuove Tecnologie in Medicina e Chirurgia, Università di Pisa, Italia.
authors: Cristina
authors: C
authors: Viaggi
authors: Laboratories of Pharmacology, Department of Health Sciences, University of Milan, Italy.
authors: Zuzana
authors: Z
authors: Gombalova
authors: Laboratories of Pharmacology, Department of Health Sciences, University of Milan, Italy.
authors: Elisa
authors: E
authors: Latorre
authors: Experimental Oncology Department, European Institute of Oncology, Milan, Italy.
authors: Massimiliano
authors: M
authors: Mazza
authors: Dipartimento di Ricerca Traslazionale e delle Nuove Tecnologie in Medicina e Chirurgia, Università di Pisa, Italia.
authors: Francesca
authors: F
authors: Vaglini
authors: Laboratories of Pharmacology, Department of Health Sciences, University of Milan, Italy.
authors: Anna Maria
authors: AM
authors: Di Giulio
authors: Laboratories of Pharmacology, Department of Health Sciences, University of Milan, Italy.
authors: Alfredo
authors: A
authors: Gorio
mesh_terms: D000818:Animals; D000941:Antigens / Q000378:metabolism; D000951:Antigens, Neoplasm / Q000235:genetics / Q000378:metabolism; D064987:Cell- and Tissue-Based Therapy / Q000379:methods*; D002795:Choline O-Acetyltransferase / Q000378:metabolism; D003342:Corpus Striatum / Q000601:surgery*; D004195:Disease Models, Animal; D004921:Erythropoietin / Q000235:genetics / Q000378:metabolism*; D020267:MPTP Poisoning / Q000378:metabolism / Q000473:pathology / Q000628:therapy*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D009069:Movement Disorders / Q000209:etiology / Q000628:therapy; D053580:Muscle Strength / Q000502:physiology; D009419:Nerve Tissue Proteins / Q000378:metabolism; D058953:Neural Stem Cells / Q000378:metabolism / Q000637:transplantation*; D011509:Proteoglycans / Q000378:metabolism; D020127:Recovery of Function / Q000502:physiology*; D014446:Tyrosine 3-Monooxygenase / Q000235:genetics / Q000378:metabolism; D005680:gamma-Aminobutyric Acid / Q000378:metabolism; D000099216:Chondroitin Sulfate Proteoglycan 4
chemical_list: D000941:Antigens; D000951:Antigens, Neoplasm; D002795:Choline O-Acetyltransferase; D004921:Erythropoietin; D009419:Nerve Tissue Proteins; D011509:Proteoglycans; D014446:Tyrosine 3-Monooxygenase; D005680:gamma-Aminobutyric Acid; D000099216:Chondroitin Sulfate Proteoglycan 4; C440529:UBC antigen
keywords: MPTP; Parkinson’s disease; adult neural stem cells; cell therapy; erythropoietin; regenerative medicine