Abstract

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.

Original languageEnglish
Pages (from-to)77-89
Number of pages13
JournalBiomaterials
Volume142
DOIs
Publication statusPublished - Oct 1 2017

Fingerprint

Nerve Growth Factors
Platelets
Parkinson Disease
Blood Platelets
Therapeutics
Hot Temperature
Dopaminergic Neurons
Plasmas
Fibrinogen
Neurons
Cerebrospinal fluid
Proteins
Intranasal Administration
1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine
Blood Component Removal
Neurotoxins
Substantia Nigra
Fibrin
Viruses
Hepacivirus

Keywords

  • Growth factors
  • MPTP
  • Neuroprotection
  • Neurotrophins
  • Parkinson
  • Platelet lysate

ASJC Scopus subject areas

  • Bioengineering
  • Ceramics and Composites
  • Biophysics
  • Biomaterials
  • Mechanics of Materials

Cite this

Tailor-made purified human platelet lysate concentrated in neurotrophins for treatment of Parkinson's disease. / Chou, Ming Li; Wu, Joe Wei; Gouel, Flore; Jonneaux, Aurélie; Tillerman, Kelly; Renn, Ting Yi; Laloux, Charlotte; Chang, Hung Ming; Lin, Liang Tzung; Devedjian, Jean Christophe; Devos, David; Burnouf, Thierry.

In: Biomaterials, Vol. 142, 01.10.2017, p. 77-89.

Research output: Contribution to journalArticle

Chou, Ming Li ; Wu, Joe Wei ; Gouel, Flore ; Jonneaux, Aurélie ; Tillerman, Kelly ; Renn, Ting Yi ; Laloux, Charlotte ; Chang, Hung Ming ; Lin, Liang Tzung ; Devedjian, Jean Christophe ; Devos, David ; Burnouf, Thierry. / Tailor-made purified human platelet lysate concentrated in neurotrophins for treatment of Parkinson's disease. In: Biomaterials. 2017 ; Vol. 142. pp. 77-89.
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AU - Chou, Ming Li

AU - Wu, Joe Wei

AU - Gouel, Flore

AU - Jonneaux, Aurélie

AU - Tillerman, Kelly

AU - Renn, Ting Yi

AU - Laloux, Charlotte

AU - Chang, Hung Ming

AU - Lin, Liang Tzung

AU - Devedjian, Jean Christophe

AU - Devos, David

AU - Burnouf, Thierry

PY - 2017/10/1

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