諸如汽車事故或戰(zhàn)時戰(zhàn)斗一樣的災(zāi)難中的屠殺事件往往反映在涉及的人的機體內(nèi)。一種嚴重創(chuàng)傷能使血管和神經(jīng)切斷,、骨折和細胞殘骸散落于全身,。
神經(jīng)嚴重損傷是最具挑戰(zhàn)性傷口之一,。這就是槍傷或刺傷、車禍?zhǔn)芎φ呒皯?zhàn)場上受傷士兵這些人的傷口類型,。
一篇發(fā)表在PLoS ONE上的文章報道了一系列令人吃驚的細胞,,它們可能具有神經(jīng)移植的潛力。
在大鼠研究中,研究小組發(fā)現(xiàn)背根神經(jīng)節(jié)神經(jīng)元(即DRG細胞)幫助產(chǎn)生稠密,、健康的神經(jīng),,不引起免疫系統(tǒng)的不必要注意。
這項發(fā)現(xiàn)為更好地治療美國每年不止35萬的外周神經(jīng)嚴重受損的患者向前推進了一步,。
對于這些嚴重的損傷來說,,有許多種選擇,但沒有一種是理想的,。
因為受損神經(jīng)的自我修復(fù),,神經(jīng)的兩個分離但健康的部分必須通過迷宮般組織找出彼此并連結(jié)在一起。對于一個非常小的傷口而言,,這會自然地發(fā)生,,就像皮膚小切口的愈合,但是對某些神經(jīng)損傷,,切口只是實在太大,,神經(jīng)沒有干預(yù)將長不回來了,。
對于醫(yī)生來說,,首選是從患者自身的其他地方移植神經(jīng)組織到受傷地方,如大腿神經(jīng)的一部分,。移植神經(jīng)起腳手架作用,,即新神經(jīng)生長部分的路標(biāo)與切口間的橋梁。既然組織來自患者,,機體就會接納新新神經(jīng),,不對它進行排斥。
但對許多患者來說,,不選擇這種治療,。他們可能機體其他部分也有嚴重的傷口,以致沒有可用的額外神經(jīng)組織,。另一選擇就是從尸體或動物上移植神經(jīng),,但那些神經(jīng)將帶來其他的挑戰(zhàn),如終身服用強效免疫抑制藥物,,因此很少用那些神經(jīng)組織,。
神經(jīng)外科醫(yī)生使用的一種技術(shù)就是產(chǎn)神經(jīng)導(dǎo)管(NeuraGen Nerve Guide),它是一種中空的,、可吸收的膠原管,,通過它神經(jīng)纖維能生長并找到彼此。這種技術(shù)常用于修復(fù)不到半英寸長的短距離神經(jīng)損傷,。
在這項發(fā)表于PLoS One 上的研究中,,研究小組在大鼠上比較了幾種試圖搭橋約半英寸切口的方法。研究小組從不同類型大鼠移植神經(jīng)細胞到傷口處,比較了單用生神經(jīng)技術(shù)(NeuraGen technology)及其與DRG細胞,、神經(jīng)鞘細胞等其他細胞成對使用時的結(jié)果,。
4個月后,發(fā)現(xiàn)裝備有DRG細胞或神經(jīng)鞘細胞的導(dǎo)管生長出了健康神經(jīng),。另外,,與神經(jīng)鞘細胞相比,DRG細胞引起更少的免疫系統(tǒng)不必要注意,,神經(jīng)鞘細胞引起免疫系統(tǒng)的注意是巨噬細胞的兩倍,,大大多于免疫化合物γ-干擾素。
而Schwann 和DRG都在神經(jīng)再生中起作用,,更常認為Schwann細胞是神經(jīng)移植過程中潛在搭檔,,即使它們因為免疫系統(tǒng)對其反應(yīng)而有相當(dāng)?shù)奶魬?zhàn)性。
常規(guī)觀點認為Schwann細胞在再生過程中起決定性作用,,但是DRG細胞也發(fā)揮重要作用,。DRG細胞可能是神經(jīng)再生的豐富資源。在一項相關(guān)研究中,,正在實驗室里通過伸拉這些細胞來創(chuàng)造DRG細胞,,誘騙它們每三周生長約一英寸長。這個主意是在實驗室里使神經(jīng)生長幾英寸長,,然后將它們移植到患者上,,而不是手術(shù)后等待幾個月時間讓神經(jīng)末梢在患者體內(nèi)游歷最后對接的這段距離。(生物谷bioon.com)
doi:10.1371/journal.pone.0031675
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PMID:
Allotransplanted Neurons Used to Repair Peripheral Nerve Injury Do Not Elicit Overt Immunogenicity
Allotransplanted Neurons Used to Repair Peripheral Nerve Injury Do Not Elicit Overt Immunogenicity
ABSTRACT A major problem hindering the development of autograft alternatives for repairing peripheral nerve injuries is immunogenicity. We have previously shown successful regeneration in transected rat sciatic nerves using conduits filled with allogeneic dorsal root ganglion (DRG) cells without any immunosuppression. In this study, we re-examined the immunogenicity of our DRG neuron implanted conduits as a potential strategy to overcome transplant rejection. A biodegradable NeuraGen? tube was infused with pure DRG neurons or Schwann cells cultured from a rat strain differing from the host rats and used to repair 8 mm gaps in the sciatic nerve. We observed enhanced regeneration with allogeneic cells compared to empty conduits 16 weeks post-surgery, but morphological analyses suggest recovery comparable to the healthy nerves was not achieved. The degree of regeneration was indistinguishable between DRG and Schwann cell allografts although immunogenicity assessments revealed substantially increased presence of Interferon gamma (IFN-γ) in Schwann cell allografts compared to the DRG allografts by two weeks post-surgery. Macrophage infiltration of the regenerated nerve graft in the DRG group 16 weeks post-surgery was below the level of the empty conduit (0.56 fold change from NG; p<0.05) while the Schwann cell group revealed significantly higher counts (1.29 fold change from NG; p<0.001). Major histocompatibility complex I (MHC I) molecules were present in significantly increased levels in the DRG and Schwann cell allograft groups compared to the hollow NG conduit and the Sham healthy nerve. Our results confirmed previous studies that have reported Schwann cells as being immunogenic, likely due to MHC I expression. Nerve gap injuries are difficult to repair; our data suggest that DRG neurons are superior medium to implant inside conduit tubes due to reduced immunogenicity and represent a potential treatment strategy that could be preferable to the current gold standard of autologous nerve transplant.