Contributions
Abstract: P512
Type: Poster
Abstract Category: Pathology and pathogenesis of MS - 20 Repairing mechanisms
Astrocytes and oligodendrocytes make tight glial network providing trophic, structural and metabolic support to neurons. In the CNS oligodendrocytes, as part of glial syncytium, are extensively coupled to astrocytes through making heterologous gap junctions on their somata or outer surface of myelin. Molecular disruption of astrocytes-oligodendrocytes communication (loss of Connexin43/Connexin47 connectivity) and thus its effect on neuronal function has been reported in demyelinating diseases. Loss of Cx43 in astrocytes has been shown to have a direct correlation with the extent of demyelination and severity of disease in Multiple Sclerosis and Neuromyelitis Optica. Remyelination of adult axons is known to provide trophic support, rescue the lost function and protect neurons from subsequent axonal degeneration. Our preliminary data showed that transplantation of mouse and human induced pluripotent stem cells (iPSCs)-derived neuroglial precursors in adult demyelination condition results in functional remyelination of host axons. Although grafted cells differentiated mainly into oligodendrocytes, they also generated considerable amounts of astrocytes (~ 20%). Excellent integration of graft-derived oligodendrocytes in the adult CNS was concurrent with considerable astrogliosis (GFAP+/Nestin+) of both endogenous and exogenous sources. The possible impact of (reactivated) astrocytes (and their communication with the graft-derived oligodendrocytes through different connexins) on the observed successful remyelination has not been addressed. Whether graft derived cells can help reconstruction of lost glial syncytium in demyelinating lesion remains elusive.
Our preliminary data showed that both mouse and human iPS-derived oligodendrocytes expressed Cx47 on their somata and in paranodes where they nicely connected to astrocytic Cx43. Future experiments will reveal the expression of Cx43 or Cx30 in the graft-derived astrocytes, Cx32 and Cx29 in the graft-derived oligodendrocytes, the connection between the endogenous or exogenous astrocytes and/or the endogenous/exogenous oligodendrocytes.
The results of this study will highlight the involvement of astroglial network in the biology of myelin regeneration. SM is recipient of an ECTRIMS post-doctoral fellowship.
Disclosure:
Sabah Mozafari: nothing to disclose
Cecilia Laterza: nothing to disclose
Marc Ehrlic: nothing to disclose
Tanja Kuhlmann: nothing to disclose
Gianvito Martino: nothing to disclose
Anne Baron-Van Evercooren: nothing to disclose
Abstract: P512
Type: Poster
Abstract Category: Pathology and pathogenesis of MS - 20 Repairing mechanisms
Astrocytes and oligodendrocytes make tight glial network providing trophic, structural and metabolic support to neurons. In the CNS oligodendrocytes, as part of glial syncytium, are extensively coupled to astrocytes through making heterologous gap junctions on their somata or outer surface of myelin. Molecular disruption of astrocytes-oligodendrocytes communication (loss of Connexin43/Connexin47 connectivity) and thus its effect on neuronal function has been reported in demyelinating diseases. Loss of Cx43 in astrocytes has been shown to have a direct correlation with the extent of demyelination and severity of disease in Multiple Sclerosis and Neuromyelitis Optica. Remyelination of adult axons is known to provide trophic support, rescue the lost function and protect neurons from subsequent axonal degeneration. Our preliminary data showed that transplantation of mouse and human induced pluripotent stem cells (iPSCs)-derived neuroglial precursors in adult demyelination condition results in functional remyelination of host axons. Although grafted cells differentiated mainly into oligodendrocytes, they also generated considerable amounts of astrocytes (~ 20%). Excellent integration of graft-derived oligodendrocytes in the adult CNS was concurrent with considerable astrogliosis (GFAP+/Nestin+) of both endogenous and exogenous sources. The possible impact of (reactivated) astrocytes (and their communication with the graft-derived oligodendrocytes through different connexins) on the observed successful remyelination has not been addressed. Whether graft derived cells can help reconstruction of lost glial syncytium in demyelinating lesion remains elusive.
Our preliminary data showed that both mouse and human iPS-derived oligodendrocytes expressed Cx47 on their somata and in paranodes where they nicely connected to astrocytic Cx43. Future experiments will reveal the expression of Cx43 or Cx30 in the graft-derived astrocytes, Cx32 and Cx29 in the graft-derived oligodendrocytes, the connection between the endogenous or exogenous astrocytes and/or the endogenous/exogenous oligodendrocytes.
The results of this study will highlight the involvement of astroglial network in the biology of myelin regeneration. SM is recipient of an ECTRIMS post-doctoral fellowship.
Disclosure:
Sabah Mozafari: nothing to disclose
Cecilia Laterza: nothing to disclose
Marc Ehrlic: nothing to disclose
Tanja Kuhlmann: nothing to disclose
Gianvito Martino: nothing to disclose
Anne Baron-Van Evercooren: nothing to disclose