A Nanoformulation-Mediated Multifunctional Stem Cell Therapy with Improved Beta-Amyloid Clearance and Neural Regeneration for Alzheimer's Disease.
Adv Mater
; 33(13): e2006357, 2021 Apr.
Article
em En
| MEDLINE
| ID: mdl-33624894
ABSTRACT
Alzheimer's disease (AD) is a common dementia that is currently incurable. The existing treatments can only moderately relieve the symptoms of AD to slow down its progress. How to achieve effective neural regeneration to ameliorate cognitive impairments is a major challenge for current AD treatment. Here, the therapeutic potential of a nanoformulation-mediated neural stem cell (NSC) therapy capable of simultaneous Aß clearance and neural regeneration is investigated in a murine model. Genetically engineered NSCs capable of stably and continuously expressing neprilysin (NEP) are developed to enhance Aß degradation and NSC survival in the brain. A PBAE-PLGA-Ag2 S-RA-siSOX9 (PPAR-siSOX9) nanoformulation with high gene/drug deliverability is synthesized to overcome AD microenvironment-associated adverse effects and to promote neuronal differentiation of the NEP-expressing NSCs. For achieving accurate stereotactic transplantation, Ag2 S quantum-dot-based fluorescence imaging is used to guide NSC transplantation in real time. This strategy shows numerous benefits, including efficient and long-lasting Aß degradation, improved neural regeneration, and accurate cell transplantation. It is shown that a single administration of this therapy achieves long-term efficacy (6 months) with respect to memory reversal and improvement of learning deficits.
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Texto completo:
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Base de dados:
MEDLINE
Assunto principal:
Precursor de Proteína beta-Amiloide
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Transplante de Células-Tronco
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Nanomedicina
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Doença de Alzheimer
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Regeneração Nervosa
Limite:
Animals
Idioma:
En
Ano de publicação:
2021
Tipo de documento:
Article