Pluchino Stefano, Zanotti Lucia, Rossi Barbara, Brambilla Elena, Ottoboni Linda, Salani Giuliana, Martinello Marianna, Cattalini Alessandro, Bergami Alessandra, Furlan Roberto, Comi Giancarlo, Constantin Gabriela, Martino Gianvito
Neuroimmunology Unit-DIBIT, Vita-Salute University, San Raffaele Hospital, via Olgettina 58, 20132 Milan, Italy.
Nature. 2005 Jul 14;436(7048):266-71. doi: 10.1038/nature03889.
In degenerative disorders of the central nervous system (CNS), transplantation of neural multipotent (stem) precursor cells (NPCs) is aimed at replacing damaged neural cells. Here we show that in CNS inflammation, NPCs are able to promote neuroprotection by maintaining undifferentiated features and exerting unexpected immune-like functions. In a mouse model of chronic CNS inflammation, systemically injected adult syngeneic NPCs use constitutively activated integrins and functional chemokine receptors to selectively enter the inflamed CNS. These undifferentiated cells survive repeated episodes of CNS inflammation by accumulating within perivascular areas where reactive astrocytes, inflamed endothelial cells and encephalitogenic T cells produce neurogenic and gliogenic regulators. In perivascular CNS areas, surviving adult NPCs induce apoptosis of blood-borne CNS-infiltrating encephalitogenic T cells, thus protecting against chronic neural tissue loss as well as disease-related disability. These results indicate that undifferentiated adult NPCs have relevant therapeutic potential in chronic inflammatory CNS disorders because they display immune-like functions that promote long-lasting neuroprotection.
在中枢神经系统（CNS）的退行性疾病中，神经多能（干）前体细胞（NPCs）移植旨在替代受损的神经细胞。在此我们表明，在中枢神经系统炎症中，NPCs能够通过维持未分化特征并发挥意想不到的类免疫功能来促进神经保护。在慢性中枢神经系统炎症的小鼠模型中，全身注射的成年同基因NPCs利用组成性激活的整合素和功能性趋化因子受体选择性进入炎症性中枢神经系统。这些未分化细胞通过在血管周围区域积聚而在中枢神经系统炎症的反复发作中存活，在这些区域，反应性星形胶质细胞、炎症性内皮细胞和致脑炎性T细胞产生神经源性和胶质源性调节因子。在血管周围的中枢神经系统区域，存活的成年NPCs诱导血源性中枢神经系统浸润的致脑炎性T细胞凋亡，从而防止慢性神经组织损失以及与疾病相关的残疾。这些结果表明，未分化的成年NPCs在慢性炎症性中枢神经系统疾病中具有相关的治疗潜力，因为它们表现出促进持久神经保护的类免疫功能。
