Contributions
Abstract: P677
Type: Poster
Abstract Category: Therapy - disease modifying - Neurorepair
Multiple studies have highlighted the immune-regulatory, neurotrophic and neuroprotective properties of stem cells, providing the current rationale for clinical translation of cell therapy in multiple sclerosis (MS). Neural precursor cells inhibited the immune-mediated injury in experimental autoimmune encephalomyelitis (EAE), resulting in a milder long term sequel. However, to date, it has not been shown whether stem cells induce ongoing therapeutic effects in a chronic active, relapsing-progressive model of MS. Also, while Oligodendrocyte progenitor cells are the main remyelinating cell type in the adult CNS, it is not known whether these cells exhibit also therapeutic immune-regulatory effects.
We therefore examined whether human embryonic stem cell (hESC)-derived oligodendrocyte progenitor cells (hOPCs) inhibit chronic relapsing EAE in the Biozzi mouse model.
EAE was induced in Biozzi mice by immunization with spinal cord homogenate. The mice developed an acute relapse, followed by a chronic relapsing course, with active neuroinflammation, manily in the spinal cord, and typical demyelinated plaques in the spinal tracts with variable degrees of axonal injury and loss.
hESC cultures were neuralized, and then exposed to retionic acid and purmorphamine for caudalization and ventralization. hOPC enriched cultures were propagated for 7-8 weeks prior to transplantation. hOPCs were transplanted intracerebroventricularly into Biozzi mice at day 30 post-EAE induction, at remission from the first clinical relapse. Olig2+ hOPCs were detected along spinal cord meninges during the 65 days of follow-up. Following transplantation, the animals exhibited a significant milder disease, in terms of mean and cumulative clinical scores, and reduced risk of developing a second relapse, as compared to vehicle-injected EAE mice. The hOPC-transplanted mice exhibited significantly less neuroinflammation (as indicated by CD3+ T cell and IBA-1+ microglial/macrophage infiltration) and significantly less demyelination and axonal loss (as indicated by Gold-Black and Bielchowsky staining, as well as by Toluidine-blue semi-thin stained cervical spine sections).
Thus, we show here for the first time that hOPCs possess immune-regulatory and neuroprotective properties. Moreover, their beneficial effects persist long-term in vivo, following transplantation into a clinical-relevant model of chronic active MS.
Disclosure:
Tamir Ben-Hur: Scientific advisory board member of Kadimastem, Mapi Pharma, Regenera Pharma, Stem Cell Medicine.
Benjamin Reubinoff: CSO of Cell Cure Neuroscience, Scientific advisory board member of Kadimastem
Yossi Nishri, David Hampton, Etti Ben-Shushan, Siddharthan Chandran: nothing to disclose
Supported by a grant from BIRAX - The British Council
Abstract: P677
Type: Poster
Abstract Category: Therapy - disease modifying - Neurorepair
Multiple studies have highlighted the immune-regulatory, neurotrophic and neuroprotective properties of stem cells, providing the current rationale for clinical translation of cell therapy in multiple sclerosis (MS). Neural precursor cells inhibited the immune-mediated injury in experimental autoimmune encephalomyelitis (EAE), resulting in a milder long term sequel. However, to date, it has not been shown whether stem cells induce ongoing therapeutic effects in a chronic active, relapsing-progressive model of MS. Also, while Oligodendrocyte progenitor cells are the main remyelinating cell type in the adult CNS, it is not known whether these cells exhibit also therapeutic immune-regulatory effects.
We therefore examined whether human embryonic stem cell (hESC)-derived oligodendrocyte progenitor cells (hOPCs) inhibit chronic relapsing EAE in the Biozzi mouse model.
EAE was induced in Biozzi mice by immunization with spinal cord homogenate. The mice developed an acute relapse, followed by a chronic relapsing course, with active neuroinflammation, manily in the spinal cord, and typical demyelinated plaques in the spinal tracts with variable degrees of axonal injury and loss.
hESC cultures were neuralized, and then exposed to retionic acid and purmorphamine for caudalization and ventralization. hOPC enriched cultures were propagated for 7-8 weeks prior to transplantation. hOPCs were transplanted intracerebroventricularly into Biozzi mice at day 30 post-EAE induction, at remission from the first clinical relapse. Olig2+ hOPCs were detected along spinal cord meninges during the 65 days of follow-up. Following transplantation, the animals exhibited a significant milder disease, in terms of mean and cumulative clinical scores, and reduced risk of developing a second relapse, as compared to vehicle-injected EAE mice. The hOPC-transplanted mice exhibited significantly less neuroinflammation (as indicated by CD3+ T cell and IBA-1+ microglial/macrophage infiltration) and significantly less demyelination and axonal loss (as indicated by Gold-Black and Bielchowsky staining, as well as by Toluidine-blue semi-thin stained cervical spine sections).
Thus, we show here for the first time that hOPCs possess immune-regulatory and neuroprotective properties. Moreover, their beneficial effects persist long-term in vivo, following transplantation into a clinical-relevant model of chronic active MS.
Disclosure:
Tamir Ben-Hur: Scientific advisory board member of Kadimastem, Mapi Pharma, Regenera Pharma, Stem Cell Medicine.
Benjamin Reubinoff: CSO of Cell Cure Neuroscience, Scientific advisory board member of Kadimastem
Yossi Nishri, David Hampton, Etti Ben-Shushan, Siddharthan Chandran: nothing to disclose
Supported by a grant from BIRAX - The British Council