Purinergic Receptors in Spinal Cord-Derived Ependymal Stem/Progenitor Cells and Their Potential Role in Cell-Based Therapy for Spinal Cord Injury
Purinergic Receptors in Spinal Cord-Derived Ependymal Stem/Progenitor Cells and Their Potential Role in Cell-Based Therapy for Spinal Cord Injury
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DOI：
10.3727/096368914x682828
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发表时间：
2015-01-01
影响因子：
3.3
通讯作者：
Moreno-Manzano, Victoria
中科院分区：
文献类型：
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作者：
Gomez-Villafuertes, Rosa;Javier Rodriguez-Jimenez, Francisco;Moreno-Manzano, Victoria
脊髓损伤（SCI）是瘫痪的主要原因，目前没有治疗方法。SCI后，大量的ATP和其他核苷酸被创伤组织释放，导致嘌呤能受体的激活，与生长因子协调，诱导损伤重塑和修复。我们发现成年哺乳动物室管膜脊髓源性干/祖细胞（epSPCs）能够对ATP和其他核苷酸化合物产生应答，主要通过激活亲离子型P2 X（4）、P2 X（7）和亲代谢型P2 Y（1）和P2 Y（4）嘌呤能受体。来自健康大鼠的epSPC与SCI后获得的epSPC之间的比较研究显示，epSPC中P2 Y（1）受体下调，同时P2 Y（4）受体上调。此外，严重创伤性挫伤后的脊髓显示损伤周围P2 X（4）和P2 X（7）受体表达的早期和持续增加，当异位移植epSPC时，其完全逆转。由于epSPCi移植在SCI后与诱导的P2离子型受体的抑制平行地显著挽救神经功能，因此基于嘌呤能受体和内源性修复调节的SCI治疗中的治疗替代方案的潜在途径是开放的。
Spinal cord injury (SCI) is a major cause of paralysis with no current therapies. Following SCI, large amounts of ATP and other nucleotides are released by the traumatized tissue leading to the activation of purinergic receptors that, in coordination with growth factors, induce lesion remodeling and repair. We found that adult mammalian ependymal spinal cord-derived stem/progenitor cells (epSPCs) are capable of responding to ATP and other nucleotidic compounds, mainly through the activation of the ionotropic P2X(4), P2X(7), and the metabotropic P2Y(1) and P2Y(4) purinergic receptors. A comparative study between epSPCs from healthy rats versus epSPCis, obtained after SCI, shows a downregulation of P2Y(1) receptor together with an upregulation of P2Y(4) receptor in epSPCis. Moreover, spinal cord after severe traumatic contusion shows early and persistent increases in the expression of P2X(4) and P2X(7) receptors around the injury, which are completely reversed when epSPCis were ectopically transplanted. Since epSPCi transplantation significantly rescues neurological function after SCI in parallel to inhibition of the induced P2 ionotropic receptors, a potential avenue is open for therapeutic alternatives in SCI treatments based on purinergic receptors and the endogenous reparative modulation.