Stem Cells Transl Med：干细胞疗法由猫到人

林辉

来源：生物谷 2016-02-03 16:22
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2016年2月3日 讯 /生物谷BIOON/ --当小猫Bob来到加州大学戴维斯分校兽医医院的时候，它已经用光了它的九条命；由于口腔炎症的折磨，Bob已经被拔掉了所有的牙齿试图要与这种名为猫类慢性龈口炎（FCGS）的疾病作斗争，最后小Bob进入到了一项临床试验中接受了新型的干细胞疗法进行治疗。Bob和其它小猫咪一样很幸运地进入到了这项临床试验，试验很成功，Bob获得了新生。$ D0 y8 s$ f. z: v. H) o
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研究者将这项研究的结果发表在了Stem Cells Translational Medicine杂志上；文章中研究人员首次利用干细胞疗法成功且有效地治疗了猫类的慢性龈口炎疾病；当研究者Arzi目睹了很多因治疗慢性龈口炎而失去所有牙齿的猫咪后，他就开启了专门治疗猫类这种疾病的临床试验；猫类慢性龈口炎是一种难以治疗的疾病，研究者经常会看到有些猫咪对传统的疗法并没有任何反应，于是他们决定利用干细胞疗法来试试；首先他们利用猫机体自身的脂肪衍生的干细胞，对干细胞进行处理并且进行特性分析，随后再将这些处理后的干细胞对猫进行静脉注射来降低猫机体的炎性表现，并且促进组织再生；研究人员同时还鉴别出了一种有用的生物标志物，其可以帮助确定是否猫会对干细胞疗法产生反应。2 q5 f) B& D8 d* n6 v
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Arzi说道，我们首次利用这种新型技术来对哺乳动物进行试验，作为一种动物疾病，猫类慢性龈口炎疾病或许就可以作为一种新型有效的模型来帮助开发治疗人类慢性口腔炎症疾病的新疗法。# }$ K) A1 _) O6 x9 l
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研究者Nasim Fazel此前就从事猫类慢性龈口炎和人类慢性口腔炎性疾病的组织病理学特性及血液炎性标志物的相关研究。口腔扁平苔癣是一种类似于猫类慢性龈口炎的T细胞介导的慢性炎性粘膜疾病，Fazel表示，我们很高兴这项疾病取得了突破性的进展，因为猫类疾病的表现同人类口腔扁平苔癣的病理学表现非常相似，基于以上研究，目前研究者已经提交了一项申请，来建立人类临床试验，利用间质干细胞疗法来治疗人类的口腔扁平苔癣，相信通过研究人员后期不懈的努力他们将在这一领域的研究取得新的研究成果* r4 k4 p8 \9 ]/ W3 T, r' r

林辉

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doi:10.5966/sctm.2015-0127
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Therapeutic Efficacy of Fresh, Autologous Mesenchymal Stem Cells for Severe Refractory Gingivostomatitis in Cats4 m7 [* R5 G8 Q  `

* J) t0 w. }1 u8 G. p+ A* u2 T/ nBoaz Arzia, Emily Mills-Kob, Frank J.M. Verstraetea, Amir Kolb, Naomi J. Walkerb, Megan R. Badgleyc, Nasim Fazeld, William J. Murphyd, Natalia Vapniarskye and Dori L. Borjessonb* \. ~- `( Z* W6 y5 `0 m/ E
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0 R( m3 e1 f0 B( v  H2 ?. C+ sMesenchymal stem cells (MSCs) are a promising therapy for immune-mediated and inflammatory disorders, because of their potent immunomodulatory properties. In this study, we investigated the use of fresh, autologous, adipose-derived MSCs (ASCs) for feline chronic gingivostomatitis (FCGS), a chronic, debilitating, idiopathic, oral mucosal inflammatory disease. Nine cats with refractory FCGS were enrolled in this pilot study. Each cat received 2 intravenous injections of 20 million autologous ASCs, 1 month apart. Oral biopsies were taken before and at 6 months after the first ASC injection. Blood immune cell subsets, serum protein, and cytokine levels were measured at 0, 1, 3, and 6 months after treatment to assess immunomodulatory effects. Seven of the 9 cats completed the study. Five cats responded to treatment by either complete clinical remission (n = 3) or substantial clinical improvement (n = 2). Two cats were nonresponders. Cats that responded to treatment also exhibited systemic immunomodulation demonstrated by decreased numbers of circulating CD8+ T cells, a normalization of the CD4/CD8 ratio, decreased neutrophil counts, and interferon-γ and interleukin (IL)-1β concentration, and a temporary increase in serum IL-6 and tumor necrosis factor-α concentration. No clinical recurrence has occurred following complete clinical remission (follow-up of 6–24 months). In this study, cats with <15% cytotoxic CD8 T cells with low expression of CD8 (CD8lo) cells were 100% responsive to ASC therapy, whereas cats with >15% CD8lo cells were nonresponders. The relative absence of CD8lo cells may be a biomarker to predict response to ASC therapy, and may shed light on pathogenesis of FCGS and mechanisms by which ASCs decrease oral inflammation and affect T-cell phenotype.
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