Human olfactory mesenchymal stromal cell transplantation ameliorates experimental autoimmune encephalomyelitis revealing an inhibitory role for IL16 on myelination.
Human olfactory mesenchymal stromal cell transplantation ameliorates experimental autoimmune encephalomyelitis revealing an inhibitory role for IL16 on myelination.
复制标题
人嗅间充质基质细胞移植改善实验性自身免疫性脑脊髓炎揭示IL 16对髓鞘形成的抑制作用
DOI：
10.1186/s40478-022-01316-9
复制
发表时间：
2022-01-29
影响因子：
7.1
通讯作者：
Barnett SC
中科院分区：
文献类型：
--
作者：
Lindsay SL;Molęda AM;MacLellan LM;Keh SM;McElroy DE;Linington C;Goodyear CS;Barnett SC
骨髓间充质干细胞（bone marrow mesenchymal stromal cell，hBM-MSCs）移植是治疗自身免疫性脱髓鞘疾病多发性硬化（multiple sclerosis，MS）的有效方法之一。然而，考虑到它们在体外增强髓鞘形成的能力，我们假设人嗅粘膜来源的MSC（hOM-MSC）可能具有适合CNS修复的额外特性。在此，我们已经使用实验性自身免疫性脑脊髓炎（EAE）模型检查了hOM-MSC相对于hBM-MSC的功效。如果在症状性疾病的初始发作期间递送，则两种MSC类型均改善疾病。然而，只有hOM-MSC改善疾病的结果，如果在建立的疾病，当动物有严重的神经功能缺损。脊髓损伤的组织学分析显示hOM-MSC移植减少了血脑屏障破坏和炎性细胞募集，并增强了轴突存活。在hOM-MSC治疗后的早期时间点，动物具有降低的循环IL-16水平，这反映在免疫细胞分泌IL-16的能力和脊髓炎性病变中的IL-16水平两者中。进一步的体外研究揭示了IL-16对少突胶质细胞分化和髓鞘形成的抑制作用。此外，在hOM-MSC存在下，脱髓鞘后生物活性IL-16的可用性降低。结合起来，我们的数据表明，人hOM-MSC可能具有治疗效益，在MS的治疗通过IL-16介导的途径，特别是如果在主动脱髓鞘和炎症。
One of the therapeutic approaches for the treatment of the autoimmune demyelinating disease, multiple sclerosis (MS) is bone marrow mesenchymal stromal cell (hBM-MSCs) transplantation. However, given their capacity to enhance myelination in vitro, we hypothesised that human olfactory mucosa-derived MSCs (hOM-MSCs) may possess additional properties suitable for CNS repair. Herein, we have examined the efficacy of hOM-MSCs versus hBM-MSCs using the experimental autoimmune encephalomyelitis (EAE) model. Both MSC types ameliorated disease, if delivered during the initial onset of symptomatic disease. Yet, only hOM-MSCs improved disease outcome if administered during established disease when animals had severe neurological deficits. Histological analysis of spinal cord lesions revealed hOM-MSC transplantation reduced blood–brain barrier disruption and inflammatory cell recruitment and enhanced axonal survival. At early time points post-hOM-MSC treatment, animals had reduced levels of circulating IL-16, which was reflected in both the ability of immune cells to secrete IL-16 and the level of IL-16 in spinal cord inflammatory lesions. Further in vitro investigation revealed an inhibitory role for IL-16 on oligodendrocyte differentiation and myelination. Moreover, the availability of bioactive IL-16 after demyelination was reduced in the presence of hOM-MSCs. Combined, our data suggests that human hOM-MSCs may have therapeutic benefit in the treatment of MS via an IL-16-mediated pathway, especially if administered during active demyelination and inflammation.
登录
查看更多内容
影响因子：
48
作者：
Connick, Peter;Kolappan, Madhan;Crawley, Charles;Webber, Daniel J.;Patani, Rickie;Michell, Andrew W.;Du, Ming-Qing;Luan, Shi-Lu;Altmann, Daniel R.;Thompson, Alan J.;Compston, Alastair;Scott, Michael A.;Miller, David H.;Chandran, Siddharthan
通讯作者：
Chandran, Siddharthan
DOI：
10.1097/nen.0b013e3181f97392
发表时间：
2010-11-01
影响因子：
3.2
作者：
Gordon, David;Pavlovska, Gordana;Scolding, Neil J.
通讯作者：
Scolding, Neil J.
影响因子：
3.7
作者：
Glenn, Justin D.;Smith, Matthew D.;Whartenby, Katharine A.
通讯作者：
Whartenby, Katharine A.
DOI：
10.1084/jem.165.4.1230
发表时间：
1987-04-01
期刊：
The Journal of experimental medicine
影响因子：
--
作者：
Funke I;Hahn A;Rieber EP;Weiss E;Riethmüller G
通讯作者：
Riethmüller G
DOI：
10.1073/pnas.76.1.514
发表时间：
1979-01-01
影响因子：
11.1
作者：
BOTTENSTEIN, JE;SATO, GH
通讯作者：
SATO, GH