Original article Heterogeneity of local tissue microenvironment influences differentiation of oligodendroglial progenitors

Sypecka, Joanna; Sarnowska, Anna

doi:10.5114/fn.2013.35952

Cited by 11 publications

(14 citation statements)

References 50 publications

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“…To study spinal cord pathology or reparative mechanisms, the experiments should preferably be looked upon in the context of the spinal cord microenvironment [ 6 , 17 – 19 ]. As we proved before [ 20 , 21 ] either the spinal cord or the brain environment exerts a markedly different influence on cultured cells. In order to prove this, transverse organotypic spinal slice cultures were established [ 22 , 23 ].…”

Section: Introductionmentioning

confidence: 60%

The Organotypic Longitudinal Spinal Cord Slice Culture for Stem Cell Study

Sypecka

Koniusz

Kawalec

et al. 2015

Stem Cells International

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The objective of this paper is to describe in detail the method of organotypic longitudinal spinal cord slice culture and the scientific basis for its potential utility. The technique is based on the interface method, which was described previously and thereafter was modified in our laboratory. The most important advantage of the presented model is the preservation of the intrinsic spinal cord fiber tract and the ventrodorsal polarity of the spinal cord. All the processes occurring during axonal growth, regeneration, synapse formation, and myelination could be visualized while being cultured in vitro for up to 4-5 weeks after the slices had been isolated. Both pups and adult animals can undergo the same, equally efficient procedures when going by the protocol in question. The urgent need for an appropriate in vitro model for spinal cord regeneration results from a greater number of clinical trials concerning regenerative medicine in the spinal cord injury and from still insufficient knowledge of the molecular mechanisms involved in the neuroreparative processes. The detailed method of organotypic longitudinal spinal cord slice culture is accompanied by examples of its application to studying biological processes to which both the CNS inhabiting and grafted cells are subjected.

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Section: Introductionmentioning

confidence: 60%

The Organotypic Longitudinal Spinal Cord Slice Culture for Stem Cell Study

Sypecka

Koniusz

Kawalec

et al. 2015

Stem Cells International

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“…Their sensitivity makes them vulnerable to excitotoxic insults but OPCs are also susceptible to external manipulation for the purpose of favoring the desired regenerative processes. Moreover, their fate-choice and maturation was significantly modified in the vicinity of the spinal cord slices [78, 79]. The reports published by other groups revealed the region-specific multipotentiality of these glia-committed progenitors [80, 81].…”

Section: Discussionmentioning

confidence: 99%

The Neuroprotective Effect Exerted by Oligodendroglial Progenitors on Ischemically Impaired Hippocampal Cells

Sypecka

Sarnowska

2013

Mol Neurobiol

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Oligodendrocyte progenitor cells (OPCs) are the focus of intense research for the purpose of cell replacement therapies in acquired or inherited neurodegenerative disorders, accompanied by ongoing hypo/demyelination. Recently, it has been postulated that these glia-committed cells exhibit certain properties of neural stem cells. Advances in stem cell biology have shown that their therapeutic effect could be attributed to their ability to secret numerous active compounds which modify the local microenvironment making it more susceptible to restorative processes. To verify this hypothesis, we set up an ex vivo co-culture system of OPCs isolated from neonatal rat brain with organotypic hippocampal slices (OHC) injured by oxygen-glucose deprivation (OGD). The presence of OPCs in such co-cultures resulted in a significant neuroprotective effect manifesting itself as a decrease in cell death rate and as an extension of newly formed cells in ischemically impaired hippocampal slices. A microarray analysis of broad spectrum of trophic factors and cytokines expressed by OPCs was performed for the purpose of finding the factor(s) contributing to the observed effect. Three of them—BDNF, IL-10 and SCF—were selected for the subsequent functional assays. Our data revealed that BDNF released by OPCs is the potent factor that stimulates cell proliferation and survival in OHC subjected to OGD injury. At the same time, it was observed that IL-10 attenuates inflammatory processes by promoting the formation of the cells associated with the immunological response. Those neuroprotective qualities of oligodendroglia-biased progenitors significantly contribute to anticipating a successful cell replacement therapy.

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“…Many lipid biosynthetic enzymes are regulated by mTORC1 and mTORC2 in other systems (Yecies et al, 2011;Ricoult and Manning, 2013), and the Wood laboratory has previously shown that there are a plethora of mTOR complex targets, including lipid enzymes, which are modulated upon pharmacological inhibition of mTOR in vitro (Tyler et al, 2011). There is increasing evidence for regional heterogeneity of oligodendrocytes (Reynolds and Herschkowitz, 1987;Hardy et al, 1996;Riddle et al, 2006;Sypecka and Sarnowska, 2013). For example, the ablation of Fyn kinase results in differential impact on myelination in different areas of the CNS (Sperber et al, 2001).…”

Section: Discussionmentioning

confidence: 99%

Conditional Ablation of Raptor or Rictor Has Differential Impact on Oligodendrocyte Differentiation and CNS Myelination

et al. 2014

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During CNS development, oligodendrocytes, the myelinating glia of the CNS, progress through multiple transitory stages before terminating into fully mature cells. Oligodendrocyte differentiation and myelination is a tightly regulated process requiring extracellular signals to converge to elicit specific translational and transcriptional changes. Our lab has previously shown that the protein kinases, Akt and mammalian Target of Rapamycin (mTOR), are important regulators of CNS myelination in vivo. mTOR functions through two distinct complexes, mTOR complex 1 (mTORC1) and mTORC2, by binding to either Raptor or Rictor, respectively. To establish whether the impact of mTOR on CNS myelination results from unique functions of mTORC1 or mTORC2 during CNS myelination, we conditionally ablated either Raptor or Rictor in the oligodendrocyte lineage, in vivo. We show that Raptor (mTORC1) is a positive regulator of developmental CNS mouse myelination when mTORC2 is functional, whereas Rictor (mTORC2) ablation has a modest positive effect on oligodendrocyte differentiation, and very little effect on myelination, when mTORC1 is functional. Also, we show that loss of Raptor in oligodendrocytes results in differential dysmyelination in specific areas of the CNS, with the greatest impact on spinal cord myelination.

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Original article Heterogeneity of local tissue microenvironment influences differentiation of oligodendroglial progenitors

Abstract: JJo oa an nn na a S Sy yp pe ec ck ka a, , A An nn na a S Sa ar rn no ow ws sk ka a

Cited by 11 publications

References 50 publications

The Organotypic Longitudinal Spinal Cord Slice Culture for Stem Cell Study

The Organotypic Longitudinal Spinal Cord Slice Culture for Stem Cell Study

The Neuroprotective Effect Exerted by Oligodendroglial Progenitors on Ischemically Impaired Hippocampal Cells

Conditional Ablation of Raptor or Rictor Has Differential Impact on Oligodendrocyte Differentiation and CNS Myelination

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