Contributions
Abstract: P1220
Type: Poster Sessions
Abstract Category: Therapy - Neuroprotection and Repair
Background: Blocking of bone morphogenetic proteins (BMPs) is known to induce oligodendrogenesis from neural stem cells. BMPs were detected in MS lesions and in spinal cord of EAE. We have reported that anti-BMP2/4 treatment improved relapsing EAE (R-EAE) and enhanced differentiation of neuroblasts and pro-oligodendrocytes. The question whether this therapy induces immunosuppression remained unsolved.
Objective: To examine the effect of BMP2/4 blockage in R-EAE on formation of mature oligodendrocytes and on immune activity.
Methods: R-EAE-induced in SJL mice were treated with I.V anti-BMP2/4 or isotype control (IC), or vehicle, on day 9 post-immunization. BrdU was injected to 3 mice per group between days 9-18 that were sacrificed on day 18 for immunohistochemistry of BrdU+CC1+ cells in the lumbar spinal cord. Spleens, brains and spinal cords removed from 3 mice of each group at day 14 (peak of 1st relapse). Mononuclear cells (MNC) were isolated from brains and spinal cords using percoll gradient. Flow cytometry study was done for CD45+, CD4+, CD8+, CD11b+, CD19+ and CD4+Foxp3+ Tregs in the spleen and CNS and for CD4+IFNγ+ (Th1), CD4+IL-4+ (Th2) and CD4+IL-17+ (Th17) in stimulated splenocytes.
Results: Treatment with anti-BMP2/4 attenuated R-EAE: 41.7% of anti-BMP2/4 group developed score ≥1 vs. 100% and 91.7% of the IC and vehicle group, respectively. Cumulative scores: 8.3± 2.5 vs. 26.0±2.9 and 25.4±4.7, P< 0.001 and P=0.005, respectively, maximum scores: 0.8±0.3 vs. 2.1±0.2 and 1.9±0.3, P=0.004 and P=0.043, respectively. A significant induction of BrdU+CC1+ mature oligodendrocytes was detected in the lumbar spinal cord: 12.2±3.8 (anti-BMP2/4 group) vs. 0.4±0.2 (IC group), P=0.032. No significant difference in the number of CD45+ cells was observed in splenocytes, brains and spinal cords between anti-BMP2/4 group vs. IC group: 5.3±1.2 x106 vs. 7.0±0.4 x106, 3.5±0.5 X105 vs. 3.0±1.2 x105, and 2.8±0.9 x105 vs. 3.6±0.5 x105 respectively. No significant differences were found in levels of CD4+ T cells, CD8+ T cells, CD11b+ monocytes, CD19+ B cells and CD4+Foxp3+ Tregs in splenocytes and MNC of the brain and spinal cord. Anti-BMP2/4 treatment did not affect the levels of CD4+IFNγ+, CD4+IL-4+ and CD4+IL-17+ cells in splenocytes.
Conclusions: Systemic blockage of BMP-2/4 ameliorates R-EAE, accompanied by oligodendrogenesis without immunosuppression.. These results suggest a novel therapeutic approach for oligodendrogenesis/ remyelination induction in MS.
Disclosure: The study is supported by stem cell medicine Ltd.
Mausner-Fainberg K: Nothing to disclose, Golan M: Nothing to disclose , Ben Hamou M: Nothing to disclose, Karni A: Nothing to disclose
Abstract: P1220
Type: Poster Sessions
Abstract Category: Therapy - Neuroprotection and Repair
Background: Blocking of bone morphogenetic proteins (BMPs) is known to induce oligodendrogenesis from neural stem cells. BMPs were detected in MS lesions and in spinal cord of EAE. We have reported that anti-BMP2/4 treatment improved relapsing EAE (R-EAE) and enhanced differentiation of neuroblasts and pro-oligodendrocytes. The question whether this therapy induces immunosuppression remained unsolved.
Objective: To examine the effect of BMP2/4 blockage in R-EAE on formation of mature oligodendrocytes and on immune activity.
Methods: R-EAE-induced in SJL mice were treated with I.V anti-BMP2/4 or isotype control (IC), or vehicle, on day 9 post-immunization. BrdU was injected to 3 mice per group between days 9-18 that were sacrificed on day 18 for immunohistochemistry of BrdU+CC1+ cells in the lumbar spinal cord. Spleens, brains and spinal cords removed from 3 mice of each group at day 14 (peak of 1st relapse). Mononuclear cells (MNC) were isolated from brains and spinal cords using percoll gradient. Flow cytometry study was done for CD45+, CD4+, CD8+, CD11b+, CD19+ and CD4+Foxp3+ Tregs in the spleen and CNS and for CD4+IFNγ+ (Th1), CD4+IL-4+ (Th2) and CD4+IL-17+ (Th17) in stimulated splenocytes.
Results: Treatment with anti-BMP2/4 attenuated R-EAE: 41.7% of anti-BMP2/4 group developed score ≥1 vs. 100% and 91.7% of the IC and vehicle group, respectively. Cumulative scores: 8.3± 2.5 vs. 26.0±2.9 and 25.4±4.7, P< 0.001 and P=0.005, respectively, maximum scores: 0.8±0.3 vs. 2.1±0.2 and 1.9±0.3, P=0.004 and P=0.043, respectively. A significant induction of BrdU+CC1+ mature oligodendrocytes was detected in the lumbar spinal cord: 12.2±3.8 (anti-BMP2/4 group) vs. 0.4±0.2 (IC group), P=0.032. No significant difference in the number of CD45+ cells was observed in splenocytes, brains and spinal cords between anti-BMP2/4 group vs. IC group: 5.3±1.2 x106 vs. 7.0±0.4 x106, 3.5±0.5 X105 vs. 3.0±1.2 x105, and 2.8±0.9 x105 vs. 3.6±0.5 x105 respectively. No significant differences were found in levels of CD4+ T cells, CD8+ T cells, CD11b+ monocytes, CD19+ B cells and CD4+Foxp3+ Tregs in splenocytes and MNC of the brain and spinal cord. Anti-BMP2/4 treatment did not affect the levels of CD4+IFNγ+, CD4+IL-4+ and CD4+IL-17+ cells in splenocytes.
Conclusions: Systemic blockage of BMP-2/4 ameliorates R-EAE, accompanied by oligodendrogenesis without immunosuppression.. These results suggest a novel therapeutic approach for oligodendrogenesis/ remyelination induction in MS.
Disclosure: The study is supported by stem cell medicine Ltd.
Mausner-Fainberg K: Nothing to disclose, Golan M: Nothing to disclose , Ben Hamou M: Nothing to disclose, Karni A: Nothing to disclose