Tailor-made purified human platelet lysate concentrated in neurotrophins for treatment of Parkinson's disease
| Autor: | Hung-Ming Chang, Kelly Timmerman, Jean-Christophe Devedjian, Ting-Yi Renn, Liang Tzung Lin, David Devos, Ming-Li Chou, Charlotte Laloux, Aurélie Jonneaux, Thierry Burnouf, Flore Gouel, Joe-Wei Wu |
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| Rok vydání: | 2017 |
| Předmět: |
Blood Platelets
Lipopolysaccharides Male Tyrosine 3-Monooxygenase Neurotoxins Anti-Inflammatory Agents Biophysics Bioengineering Substantia nigra Hepacivirus 030204 cardiovascular system & hematology Pharmacology Neuroprotection Cell Line Diffusion Biomaterials 03 medical and health sciences chemistry.chemical_compound 0302 clinical medicine Mesencephalon medicine Animals Humans Neurotoxin Platelet Nerve Growth Factors Administration Intranasal Neuroinflammation MPTP Neurotoxicity Fibrinogen Parkinson Disease medicine.disease Blood Cell Count Mice Inbred C57BL Neostriatum nervous system chemistry Biochemistry 1-Methyl-4-phenyl-1 2 3 6-tetrahydropyridine Mechanics of Materials Ceramics and Composites Platelet lysate Microglia 030217 neurology & neurosurgery |
| Zdroj: | Biomaterials. 142:77-89 |
| ISSN: | 0142-9612 |
| Popis: | Human platelet lysates (PLs), which contain multiple neurotrophins , have been proposed for treating neurodegenerative disorders, including Parkinson's disease (PD). However, current PLs suspended in plasma have high protein content and contain fibrinogen/fibrin and, following activation, also proteolytic and thrombogenic enzymes. Upon brain administration, such PLs may saturate the cerebrospinal fluid and exert neurotoxicity. We assessed whether purified PLs, concentrated in neurotrophins, protected dopaminergic neurons in PD models. Platelet concentrates were collected by apheresis and centrifuged to eliminate plasma and recover the platelets. Platelets were lysed by freeze-thaw cycles, and the 10-fold concentrated platelet pellet lysates (PPLs) were heat-treated (at 56 °C for 30 min). The heat-treated PPLs were low in total proteins, depleted in both plasma and platelet fibrinogen , and devoid of thrombogenic and proteolytic activities . They exerted very high neuroprotective activity when non-oncogenic, Lund human mesencephalic (LUHMES) cells that had differentiated into dopaminergic neurons were exposed to the MPP + neurotoxin . Heat treatment improved the neuroprotection and inactivated the neurotoxic blood-borne hepatitis C virus . PPL did not induce inflammation in BV2 microglial cells and inhibited COX-2 expression upon lipopolysaccharide exposure. Intranasal administration in mice revealed (a) diffusion of neurotrophins in the striatum and cortex, and (b) MPTP intoxication neuroprotection in the substantia nigra and striatum and the absence of neuroinflammation. These dedicated heat-treated PPLs can be a safe and valuable candidate for a therapeutic strategy for PD. |
| Databáze: | OpenAIRE |
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