Hypoxia response element-directed expression of bFGF in dental pulp stem cells improve the hypoxic environment by targeting pericytes in SCI rats.
Hypoxia response element-directed expression of bFGF in dental pulp stem cells improve the hypoxic environment by targeting pericytes in SCI rats.
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牙髓干细胞中缺氧反应元件定向表达 bFGF 通过靶向 SCI 大鼠周细胞改善缺氧环境
DOI：
10.1016/j.bioactmat.2021.01.024
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发表时间：
2021-08
影响因子：
18.9
通讯作者：
Wang Z
中科院分区：
文献类型：
--
作者：
Zhu S;Ying Y;He Y;Zhong X;Ye J;Huang Z;Chen M;Wu Q;Zhang Y;Xiang Z;Tu Y;Ying W;Xiao J;Li X;Ye Q;Wang Z
细胞移植在脊髓损伤修复中具有巨大的潜力。碱性成纤维细胞生长因子（bFGF）已被报道对哺乳动物发育和成年神经系统具有多种神经促进作用，被认为是治疗脊髓损伤后神经损伤的一种有前景的治疗方法。人牙髓干细胞（DPSCs）是一种数量丰富、免疫排斥程度低的干细胞，可以考虑用于细胞替代治疗。本研究的目的是利用腺相关病毒（AAV-5HRE-bFGF-DPSCs）研究表达bFGF的DPSCs在五种缺氧反应因子（5HRE）的调控下在脊髓损伤修复模型中的作用。本研究发现，DPSCs可分化为CD13+周细胞，并上调N-cadherin表达，促进CD13+周细胞与血管内皮细胞的再附着。CD13+周细胞与血管内皮细胞的重新附着随后通过突起的收缩增加微血管内的血流速率。结果，红细胞数量的增加将更多的氧气输送到损伤区域，改善了脊髓损伤局部缺氧微环境。因此，本研究代表着AAV-5HRE-bFGF-DPSCs在临床脊髓损伤治疗中的潜在应用向前迈进了一步。5HRE-bFGF-DPSCs以缺氧依赖的方式分泌bFGF，使给药更加精确。CD13+周细胞通过DDC-5HT-5HT-1B调节血管直径，促进缺氧微环境的恢复。5HRE-bFGF-DPSCs可分化为CD13+周细胞，弥补脊髓损伤后CD13+周细胞的大量死亡。5HRE-bFGF-DPSCs通过N-cadherin分泌bFGF促进CD13+周细胞与血管内皮细胞的粘附。5HRE-bFGF-DPSCs通过恢复缺氧微环境和抑制自噬途径促进脊髓损伤的恢复。
Cell-based transplantation strategies possess great potential for spinal cord injury (SCI) repair. Basic fibroblast growth factor (bFGF) has been reported to have multiple neuro-promoting effects on developing and adult nervous system of mammals and considered a promising therapy for nerve injury following SCI. Human dental pulp stem cells (DPSCs) are abundant stem cells with low immune rejection, which can be considered for cell replacement therapy. The purpose of this study was to investigate the roles of DPSCs which express bFGF under the regulation of five hypoxia-responsive elements (5HRE) using an adeno-associated virus (AAV-5HRE-bFGF-DPSCs) in SCI repairing model. In this study, DPSCs were revealed to differentiate into CD13+ pericytes and up-regulate N-cadherin expression to promote the re-attachment of CD13+ pericytes to vascular endothelial cells. The re-attachment of CD13+ pericytes to vascular endothelial cells subsequently increased the flow rate of blood in microvessels via the contraction of protuberance. As a result, increased numbers of red blood cells carried more oxygen to the damaged area and the local hypoxia microenvironment in SCI was improved. Thus, this study represents a step forward towards the potential use of AAV-5HRE-bFGF-DPSCs in SCI treatment in clinic. ) 5HRE-bFGF-DPSCs secrete bFGF in a hypoxia dependent manner, making the administration more precise. CD13+ pericyte regulate vascular diameter and promote the recovery of hypoxia microenvironment via DDC-5HT-5HT-1B in SCI. 5HRE-bFGF-DPSCs can differentiate into CD13+ pericyte to compensate for the mass death of CD13+ pericyte after SCI. 5HRE-bFGF-DPSCs promote CD13+ pericyte adhesion to vascular endothelial cell by secreting bFGF through N-cadherin. 5HRE-bFGF-DPSCs promote the recovery of SCI by restoring hypoxic microenvironment and inhibit autophagy pathway.
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影响因子：
23.9
作者：
Ceto, Steven;Sekiguchi, Kohei J.;Tuszynski, Mark H.
通讯作者：
Tuszynski, Mark H.
影响因子：
5.3
作者：
Bhowmick, Saurav;D'Mello, Veera;Abdul-Muneer, P. M.
通讯作者：
Abdul-Muneer, P. M.
在模型多发性硬化病变中的原因和预防。
影响因子：
11.2
作者：
Desai RA;Davies AL;Tachrount M;Kasti M;Laulund F;Golay X;Smith KJ
通讯作者：
Smith KJ
DOI：
10.1177/1073858417731522
发表时间：
2018-10
期刊：
The Neuroscientist : a review journal bringing neurobiology, neurology and psychiatry
影响因子：
--
作者：
Almeida VM;Paiva AE;Sena IFG;Mintz A;Magno LAV;Birbrair A
通讯作者：
Birbrair A
影响因子：
6
作者：
Ahuja CS;Mothe A;Khazaei M;Badhiwala JH;Gilbert EA;van der Kooy D;Morshead CM;Tator C;Fehlings MG
通讯作者：
Fehlings MG