Human Cord Blood Derived Unrestricted Somatic Stem Cells Restore Aquaporin Channel Expression, Reduce Inflammation and Inhibit the Development of Hydrocephalus After Experimentally Induced Perinatal Intraventricular Hemorrhage.
Human Cord Blood Derived Unrestricted Somatic Stem Cells Restore Aquaporin Channel Expression, Reduce Inflammation and Inhibit the Development of Hydrocephalus After Experimentally Induced Perinatal Intraventricular Hemorrhage.
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DOI：
10.3389/fncel.2021.633185
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发表时间：
2021
影响因子：
5.3
通讯作者：
Vinukonda G
中科院分区：
文献类型：
--
作者：
Purohit D;Finkel DA;Malfa A;Liao Y;Ivanova L;Kleinman GM;Hu F;Shah S;Thompson C;Joseph E;Wolin MS;Cairo MS;La Gamma EF;Vinukonda G
脑室内出血（IVH）是一种严重的早产并发症，与脑瘫、智力残疾以及脑脊液（CSF）积聚有关。组织学上，IVH导致室管膜下胶质瘤、纤维化和室管膜壁破坏。重要的是，分别调节脑脊液分泌和吸收的水通道蛋白通道1和4 （AQP1和AQP4）的表达随着IVH而改变，并与出血性脑积水的发生有关。在甘油诱导IVH后18小时，将人脐带血来源的非限制性体细胞干细胞（USSCs）注射到兔幼犬的脑室中，我们之前证明了它具有抗炎和有益的行为作用，可以减少脑积水的程度。与对照组相比，USSC处理的IVH幼崽在第7天和第14天的心室大小减小（均P < 0.05）。组织学上，USSC治疗减少了细胞浸润和室管膜壁破坏。在脉膜丛区域，AQP1的免疫反应性和室管膜壁AQP4的表达在IVH后被抑制，但在USSC后恢复。通过分析解剖的脉络膜丛和室管膜组织的mRNA证实了其作用。转化生长因子β (TGF-β)亚型、结缔组织生长因子（CTGF）和基质金属蛋白酶9 (MMP-9) mRNA及蛋白水平在IVH后显著升高，USSC处理后恢复正常（P < 0.05）。抗炎细胞因子白细胞介素-10 (IL-10) mRNA在IVH组降低，但注射USSC后明显恢复（P < 0.05）。综上所述，USSCs通过抑制TGF-β特异性亚型、CTGF和MMP-9发挥抗炎作用，恢复IL-10，恢复水通道蛋白表达至基线水平，减少脑积水。这些结果支持使用USSCs减少早产IVH后果的可能性。
Intraventricular hemorrhage (IVH) is a severe complication of preterm birth associated with cerebral palsy, intellectual disability, and commonly, accumulation of cerebrospinal fluid (CSF). Histologically, IVH leads to subependymal gliosis, fibrosis, and disruption of the ependymal wall. Importantly, expression of aquaporin channels 1 and 4 (AQP1 and AQP4) regulating respectively, secretion and absorption of cerebrospinal fluids is altered with IVH and are associated with development of post hemorrhagic hydrocephalus. Human cord blood derived unrestricted somatic stem cells (USSCs), which we previously demonstrated to reduce the magnitude of hydrocephalus, as having anti-inflammatory, and beneficial behavioral effects, were injected into the cerebral ventricles of rabbit pups 18 h after glycerol-induced IVH. USSC treated IVH pups showed a reduction in ventricular size when compared to control pups at 7 and 14 days (both, P < 0.05). Histologically, USSC treatment reduced cellular infiltration and ependymal wall disruption. In the region of the choroid plexus, immuno-reactivity for AQP1 and ependymal wall AQP4 expression were suppressed after IVH but were restored following USSC administration. Effects were confirmed by analysis of mRNA from dissected choroid plexus and ependymal tissue. Transforming growth factor beta (TGF-β) isoforms, connective tissue growth factor (CTGF) and matrix metalloprotease-9 (MMP-9) mRNA, as well as protein levels, were significantly increased following IVH and restored towards normal with USSC treatment (P < 0.05). The anti-inflammatory cytokine Interleukin-10 (IL-10) mRNA was reduced in IVH, but significantly recovered after USSC injection (P < 0.05). In conclusion, USSCs exerted anti-inflammatory effects by suppressing both TGF-β specific isoforms, CTGF and MMP-9, recovered IL-10, restored aquaporins expression towards baseline, and reduced hydrocephalus. These results support the possibility of the use of USSCs to reduce IVH consequences in prematurity.
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影响因子：
20.1
作者：
Hatzistergos KE;Quevedo H;Oskouei BN;Hu Q;Feigenbaum GS;Margitich IS;Mazhari R;Boyle AJ;Zambrano JP;Rodriguez JE;Dulce R;Pattany PM;Valdes D;Revilla C;Heldman AW;McNiece I;Hare JM
通讯作者：
Hare JM
DOI：
10.1073/pnas.97.18.10242
发表时间：
2000-08-29
影响因子：
11.1
作者：
Jin, KL;Mao, XO;Greenberg, DA
通讯作者：
Greenberg, DA
影响因子：
11
作者：
Douglas, M. R.;Daniel, M.;Logan, A.
通讯作者：
Logan, A.
影响因子：
5.3
作者：
Campos-Ordonez, Tania;Herranz-Perez, Vicente;Gonzalez-Perez, Oscar
通讯作者：
Gonzalez-Perez, Oscar
影响因子：
--
作者：
Deren KE;Forsyth J;Abdullah O;Hsu EW;Klinge PM;Silverberg GD;Johanson CE;McAllister JP 2nd
通讯作者：
McAllister JP 2nd