Cell-Based Delivery of Interleukin-13 Directs Alternative Activation of Macrophages Resulting in Improved Functional Outcome after Spinal Cord Injury.
Cell-Based Delivery of Interleukin-13 Directs Alternative Activation of Macrophages Resulting in Improved Functional Outcome after Spinal Cord Injury.
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DOI：
10.1016/j.stemcr.2016.11.005
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发表时间：
2016-12-13
影响因子：
5.9
通讯作者：
Hendrix, Sven
中科院分区：
文献类型：
--
作者：
Dooley, Dearbhaile;Lemmens, Evi;Vangansewinkel, Tim;Le Blon, Debbie;Hoornaert, Chloe;Ponsaerts, Peter;Hendrix, Sven
迄今为止，间充质干细胞（MSC）移植治疗脊髓损伤（SCI）的效果有限。因此，我们旨在通过持续分泌抗炎细胞因子白介素-13 （IL-13）来增强MSCs的免疫调节特性。通过使用MSCs作为IL-13的载体（MSC/IL-13），我们研究了它们在脊髓损伤小鼠模型中的治疗潜力，并与非工程化MSCs进行了比较。我们发现移植的MSC/IL-13显著改善了脊髓损伤后的功能恢复，并使病变大小和脱髓鞘面积减少了40%以上。进一步对CX3CR1EGFP/+ CCR2RFP/+转基因小鼠的组织学分析表明，MSC/IL-13显著减少了常驻小胶质细胞的数量，增加了交替活化的巨噬细胞的数量。此外，MSC/ il -13处理小鼠的巨噬细胞-轴突接触数量减少了50%，表明轴突枯死减少。我们的数据提供了证据，证明MSC/IL-13移植可改善脊髓损伤小鼠模型的功能和组织病理学恢复。分泌IL-13的MSCs改善脊髓损伤后的功能和组织病理学结果MSC/IL-13处理小鼠中选择性活化的巨噬细胞数量增加MSC/IL-13处理小鼠中巨噬细胞-轴突接触减少Hendrix及其同事证明，移植MSC/IL-13可显著改善小鼠脊髓损伤后的功能和组织病理学结果。此外，MSC/IL-13显著增加了巨噬细胞的选择性活化数量，减少了巨噬细胞与轴突的接触数量。因此，MSCs可以成功地用作脊髓损伤小鼠模型中IL-13局部递送的载体。
The therapeutic effects of mesenchymal stem cell (MSC) transplantation following spinal cord injury (SCI) to date have been limited. Therefore, we aimed to enhance the immunomodulatory properties of MSCs via continuous secretion of the anti-inflammatory cytokine interleukin-13 (IL-13). By using MSCs as carriers of IL-13 (MSC/IL-13), we investigated their therapeutic potential, compared with non-engineered MSCs, in a mouse model of SCI. We show that transplanted MSC/IL-13 significantly improve functional recovery following SCI, and also decrease lesion size and demyelinated area by more than 40%. Further histological analyses in CX3CR1EGFP/+ CCR2RFP/+ transgenic mice indicated that MSC/IL-13 significantly decrease the number of resident microglia and increase the number of alternatively activated macrophages. In addition, the number of macrophage-axon contacts in MSC/IL-13-treated mice was decreased by 50%, suggesting a reduction in axonal dieback. Our data provide evidence that transplantation of MSC/IL-13 leads to improved functional and histopathological recovery in a mouse model of SCI. Use of MSCs as carriers of IL-13 in a mouse model of SCI IL-13-secreting MSCs improve functional and histopathological outcome after SCI Increase in number of alternatively activated macrophages in MSC/IL-13-treated mice Decrease in macrophage-axon contacts in MSC/IL-13-treated mice Hendrix and colleagues demonstrate that transplantation of MSC/IL-13 significantly improves both functional and histopathological outcome following SCI in mice. Furthermore, MSC/IL-13 significantly increases the number of alternatively activated macrophages and decreases the number of macrophage-axon contacts. MSCs can therefore be successfully used as carriers for the local delivery of IL-13 in a mouse model of SCI.
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影响因子：
7.5
作者：
De Vocht N;Praet J;Reekmans K;Le Blon D;Hoornaert C;Daans J;Berneman Z;Van der Linden A;Ponsaerts P
通讯作者：
Ponsaerts P
影响因子：
5.5
作者：
Geurts, Nathalie;Vangansewinkel, Tim;Hendrix, Sven
通讯作者：
Hendrix, Sven
影响因子：
5.3
作者：
Evans, Teresa A.;Barkauskas, Deborah S.;Myers, Jay T.;Hare, Elisabeth G.;You, Jing Qiang;Ransohoff, Richard M.;Huang, Alex Y.;Silver, Jerry
通讯作者：
Silver, Jerry
影响因子：
4.8
作者：
Hendrix, Sven;Kramer, Peter;Maurer, Marcus
通讯作者：
Maurer, Marcus
影响因子：
5.3
作者：
Horn, Kevin P.;Busch, Sarah A.;Hawthorne, Alicia L.;van Rooijen, Nico;Silver, Jerry
通讯作者：
Silver, Jerry