PMID- 31726669
OWN - NLM
STAT- MEDLINE
DCOM- 20200722
LR  - 20200722
IS  - 2073-4409 (Electronic)
IS  - 2073-4409 (Linking)
VI  - 8
IP  - 11
DP  - 2019 Nov 12
TI  - Combinatory Multifactor Treatment Effects on Primary Nanofiber Oligodendrocyte 
      Cultures.
LID - 10.3390/cells8111422 [doi]
LID - 1422
AB  - Multiple sclerosis (MS) is a chronic inflammatory demyelinating and 
      neurodegenerative disease of the central nervous system. Neurological deficits 
      are attributed to inflammatory demyelination, which compromises axonal function 
      and survival. These are mitigated in experimental models by rapid and often 
      complete remyelination of affected axons, but in MS this endogenous repair 
      mechanism frequently fails, leaving axons increasingly vulnerable to the 
      detrimental effects of inflammatory and metabolic stress. Understanding the 
      molecular basis of remyelination and remyelination failure is essential to 
      develop improved therapies for this devastating disease. However, recent studies 
      suggest that this is not due to a single dominant mechanism, but rather 
      represents the biological outcome of multiple changes in the lesion 
      microenvironment that combine to disrupt oligodendrocyte differentiation. This 
      identifies a pressing need to develop technical platforms to investigate 
      combinatory and/or synergistic effects of factors differentially expressed in MS 
      lesions on oligodendrocyte proliferation and differentiation. Here we describe 
      protocols using primary oligodendrocyte cultures from Bl6 mice on 384-well 
      nanofiber plates to model changes affecting oligodendrogenesis and 
      differentiation in the complex signaling environment associated with multiple 
      sclerosis lesions. Using platelet-derived growth factor (PDGF-AA), fibroblast 
      growth factor 2 (FGF2), bone morphogenetic protein 2 (BMP2) and bone 
      morphogenetic protein 4 (BMP4) as representative targets, we demonstrate that we 
      can assess their combinatory effects across a wide range of concentrations in a 
      single experiment. This in vitro model is ideal for assessing the combinatory 
      effects of changes in availability of multiple factors, thus more closely 
      modelling the situation in vivo and furthering high-throughput screening 
      possibilities.
FAU - Enz, Lukas S
AU  - Enz LS
AD  - Neurobiology, Department of Biomedicine, University Hospital Basel, University 
      Basel, Zentrum fur Lehre und Forschung, 4031 Basel, Switzerland.
FAU - Zeis, Thomas
AU  - Zeis T
AD  - Neurobiology, Department of Biomedicine, University Hospital Basel, University 
      Basel, Zentrum fur Lehre und Forschung, 4031 Basel, Switzerland.
FAU - Hauck, Annalisa
AU  - Hauck A
AUID- ORCID: 0000-0002-6853-8363
AD  - Neurobiology, Department of Biomedicine, University Hospital Basel, University 
      Basel, Zentrum fur Lehre und Forschung, 4031 Basel, Switzerland.
FAU - Linington, Christopher
AU  - Linington C
AD  - Institute of Infection, Immunity and Inflammation, College of Medical Veterinary 
      and Life Sciences, University of Glasgow, Glasgow G12 8TA, UK.
FAU - Schaeren-Wiemers, Nicole
AU  - Schaeren-Wiemers N
AUID- ORCID: 0000-0002-6554-4725
AD  - Neurobiology, Department of Biomedicine, University Hospital Basel, University 
      Basel, Zentrum fur Lehre und Forschung, 4031 Basel, Switzerland.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20191112
PL  - Switzerland
TA  - Cells
JT  - Cells
JID - 101600052
RN  - 0 (Bone Morphogenetic Protein 2)
RN  - 0 (Bone Morphogenetic Protein 4)
RN  - 0 (Platelet-Derived Growth Factor)
RN  - 0 (platelet-derived growth factor A)
RN  - 103107-01-3 (Fibroblast Growth Factor 2)
SB  - IM
MH  - Animals
MH  - Bone Morphogenetic Protein 2/pharmacology
MH  - Bone Morphogenetic Protein 4/pharmacology
MH  - Cell Differentiation/drug effects
MH  - Cell Proliferation/drug effects
MH  - Cells, Cultured
MH  - Fibroblast Growth Factor 2/pharmacology
MH  - Humans
MH  - Mice
MH  - Models, Theoretical
MH  - Multiple Sclerosis/*metabolism/therapy
MH  - Myelin Sheath/*metabolism
MH  - Nanofibers
MH  - Oligodendroglia/*cytology/drug effects/metabolism
MH  - Platelet-Derived Growth Factor/pharmacology
MH  - Primary Cell Culture/*instrumentation/methods
PMC - PMC6912369
OTO - NOTNLM
OT  - multiple sclerosis
OT  - myelin
OT  - nanofibers
OT  - oligodendrocyte
OT  - remyelination
OT  - screening
COIS- The authors declare no conflict of interest.
EDAT- 2019/11/16 06:00
MHDA- 2020/07/23 06:00
PMCR- 2019/11/01
CRDT- 2019/11/16 06:00
PHST- 2019/09/30 00:00 [received]
PHST- 2019/10/29 00:00 [revised]
PHST- 2019/11/05 00:00 [accepted]
PHST- 2019/11/16 06:00 [entrez]
PHST- 2019/11/16 06:00 [pubmed]
PHST- 2020/07/23 06:00 [medline]
PHST- 2019/11/01 00:00 [pmc-release]
AID - cells8111422 [pii]
AID - cells-08-01422 [pii]
AID - 10.3390/cells8111422 [doi]
PST - epublish
SO  - Cells. 2019 Nov 12;8(11):1422. doi: 10.3390/cells8111422.