In Vivo Phenotyping of Familial Parkinson's Disease with Human Induced Pluripotent Stem Cells: A Proof-of-Concept Study.
In Vivo Phenotyping of Familial Parkinson's Disease with Human Induced Pluripotent Stem Cells: A Proof-of-Concept Study.
Neurochem Res. 2019 Apr 15;:
Authors: Zygogianni O, Antoniou N, Kalomoiri M, Kouroupi G, Taoufik E, Matsas R
Abstract
Parkinson's disease (PD) is the second most common neurodegenerative disorder. We have previously developed a disease-in-a-dish model for familial PD using induced pluripotent stem cells (iPSCs) from two patients carrying the p.A53T α-synuclein (αSyn) mutation. By directed differentiation, we generated a model that displays disease-relevant phenotypes, including protein aggregation, compromised neurite outgrowth, axonal neuropathology and synaptic defects. Here we investigated the in vivo phenotypes of iPSCs, derived from one patient, after transplantation in a lesion mouse model established by unilateral intrastriatal 6-hydroxydopamine injection in the immunosuppressed NOD/SCID strain. Immunohistochemistry revealed that despite the disease-related characteristics that mutant cells displayed when maintained up to 70 days in vitro, they could survive and differentiate in vivo over a 12-week period. However, some differences were noted between patient-derived and control grafts, including a significant rise in αSyn immunoreactivity that might signal a first step towards pathology. Moreover, control-derived grafts appeared to integrate better than PD grafts within the host tissue extending projectio...
Source: Neurochemical Research - Category: Neuroscience Authors: Zygogianni O, Antoniou N, Kalomoiri M, Kouroupi G, Taoufik E, Matsas R Tags: Neurochem Res Source Type: research
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