Human neural precursor cells promote neurologic recovery in a viral model of multiple sclerosis.
Human neural precursor cells promote neurologic recovery in a viral model of multiple sclerosis.
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DOI：
10.1016/j.stemcr.2014.04.005
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发表时间：
2014-06-03
影响因子：
5.9
通讯作者：
Lane, Thomas E.
中科院分区：
文献类型：
--
作者：
Chen, Lu;Coleman, Ronald;Leang, Ronika;Ha Tran;Kopf, Alexandra;Walsh, Craig M.;Sears-Kraxberger, Ilse;Steward, Oswald;Macklin, Wendy B.;Loring, Jeanne F.;Lane, Thomas E.
使用病毒模型的脱髓鞘疾病多发性硬化症（MS），我们表明，椎管内移植人胚胎干细胞衍生的神经前体细胞（hNPCs）的结果在持续的临床恢复，虽然hNPCs不能检测超过8天移植后。运动技能的改善与神经炎症的减少、脱髓鞘的减少和髓鞘再生的增强有关。有证据表明，减少的神经炎症与脊髓内CD 4 + CD 25 + FOXP 3+调节性T细胞（TCRs）数量的增加相关。hNPC与活化的T细胞的共培养导致T细胞增殖减少和Treg数目增加。hNPC部分通过分泌TGF-β1和TGF-β2发挥作用。这些发现表明，暂时存在的hNPC移植在MS的动物模型中具有强大的免疫调节作用，并介导恢复。进一步研究hNPC移植的恢复作用可能有助于临床相关MS治疗的发展。hNPC的脊髓移植导致MS病毒模型中的恢复hNPC介导的恢复在不存在移植细胞的情况下发生hNPC通过增加CNS中的Treg频率而具有免疫调节性hNPC通过TGF-β1和TGF-β2依赖性途径增加Treg频率在多发性硬化症的免疫活性小鼠模型中的应用导致持续的临床恢复。尽管hNPC在8天内被排斥，但治疗的小鼠表现出神经炎症的持久减少和髓鞘再生的增强。hNPC似乎通过瞬时分泌的抗炎和髓鞘形成因子介导恢复。
Using a viral model of the demyelinating disease multiple sclerosis (MS), we show that intraspinal transplantation of human embryonic stem cell-derived neural precursor cells (hNPCs) results in sustained clinical recovery, although hNPCs were not detectable beyond day 8 posttransplantation. Improved motor skills were associated with a reduction in neuroinflammation, decreased demyelination, and enhanced remyelination. Evidence indicates that the reduced neuroinflammation is correlated with an increased number of CD4+CD25+FOXP3+ regulatory T cells (Tregs) within the spinal cords. Coculture of hNPCs with activated T cells resulted in reduced T cell proliferation and increased Treg numbers. The hNPCs acted, in part, through secretion of TGF-β1 and TGF-β2. These findings indicate that the transient presence of hNPCs transplanted in an animal model of MS has powerful immunomodulatory effects and mediates recovery. Further investigation of the restorative effects of hNPC transplantation may aid in the development of clinically relevant MS treatments. Spinal cord transplantation of hNPCs results in recovery in a viral model of MS hNPC-mediated recovery occurs in the absence of engrafted cells hNPCs are immunomodulatory through increasing the frequency of Tregs in the CNS hNPCs increase Treg frequency via a TGF-β1- and TGF-β2-dependent pathway Intraspinal transplantation of hESC-derived neural precursor cells (hNPCs) into an immunocompetent mouse model of multiple sclerosis results in sustained clinical recovery. Although hNPCs were rejected within 8 days, the treated mice exhibited long-lasting reduction in neuroinflammation and enhancement of remyelination. The hNPCs appear to mediate recovery through transiently secreted anti-inflammatory and promyelination factors.
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影响因子：
64.8
作者：
Mueller, Franz-Josef;Laurent, Louise C.;Kostka, Dennis;Ulitsky, Igor;Williams, Roy;Lu, Christina;Park, In-Hyun;Rao, Mahendra S.;Shamir, Ron;Schwartz, Philip H.;Schmidt, Nils O.;Loring, Jeanne F.
通讯作者：
Loring, Jeanne F.
影响因子：
4.4
作者：
Glass, WG;Hickey, MJ;Lane, TE
通讯作者：
Lane, TE
影响因子：
25
作者：
通讯作者：
--
影响因子：
15.9
作者：
Lane, TE;Buchmeier, MJ
通讯作者：
Buchmeier, MJ
影响因子：
48
作者：
Chetty, Sundari;Pagliuca, Felicia Walton;Honore, Christian;Kweudjeu, Anastasie;Rezania, Alireza;Melton, Douglas A.
通讯作者：
Melton, Douglas A.