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Immune characterization of mesenchymal stem cells in human umbilical cord Wharton's jelly and derived cartilage cells

机译:人脐带沃顿氏胶和衍生软骨细胞中间充质干细胞的免疫特性

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Mesenchymal stem cells derived from human umbilical cord Wharton's jelly (hWJMSCs) became prospective seed cell candidate for tissue engineering and cell-based therapy because of its variety source, easy procurement, robust proliferation, and high purity compared with bone marrow- and adipose-derived MSCs. Such neonatal stem cells can be isolated from a variety of extraembryonic tissues and appear to be more primitive and have greater multi-potentiality than their adult counterparts. In this study, we investigated the immune characters of hWJMSCs and its derived cartilage cells (hWJMSC-Cs) by detecting the expression of major histocompatibility complex I/I(MHC-I/II), costimulatory molecules (CD40, CD80 and CD86) and immune inhibitors including human leukocyte antigen G (HLA-G), indoleamine-2,3-dioxygenase (IDO), and prostaglandin E2 (PGE2). We found that hWJMSCs did not express MHC-II and costimulatory molecules, but moderately expressed MHC-I, and positively expressed immune inhibitors as HLA-G, IDO, PGE2, demonstrating their very low immunogenicity and potential to induce immune tolerance microenvironment in hosts. The results of chondrogenic differentiated hWJMSCs(hWJMSC-Cs) are similar to those of undifferentiated cells, except for the slightly elevated MHC-II and costimulators expression. Additionally, we detected cytokine profile of hWJMSCs through cytokine antibody array and verified by western blot the positive expression of immune suppression-related molecules, HGF, VEGF, TGF, and IL-10. Furthermore, to investigate the in vivo immune response of the cells, hWJMSCs-scaffold constructs were implanted into rabbits and rats, and the result showed that hWJMSCs did not elicit immune rejection in the animals. Their intermediate state between adult and embryonic stem cells makes them an ideal candidate for reprogramming to the pluripotent status. Additional studies are necessary to clarify the potential of hWJMSCs to be used in cartilage and other tissue regeneration and cell-based therapies.
机译:与骨髓和脂肪来源的骨髓相比,源自人类沃顿氏胶冻的间充质干细胞(hWJMSC)成为组织工程和基于细胞的治疗的潜在种子细胞候选者,因为其来源多样,易于获得,增殖能力强,纯度高。 MSC。这样的新生儿干细胞可以从多种胚外组织中分离出来,并且比成年的干细胞看起来更原始,具有更大的多潜能。在这项研究中,我们通过检测主要组织相容性复合体I / I(MHC-I / II),共刺激分子(CD40,CD80和CD86)的表达,研究了hWJMSCs及其衍生的软骨细胞(hWJMSC-Cs)的免疫特性。免疫抑制剂包括人白细胞抗原G(HLA-G),吲哚胺-2,3-二加氧酶(IDO)和前列腺素E2(PGE2)。我们发现hWJMSCs不表达MHC-II和共刺激分子,但是适度表达MHC-I,并积极表达免疫抑制剂,如HLA-G,IDO,PGE2,这表明它们的免疫原性很低,并具有诱导宿主免疫耐受微环境的潜力。软骨分化的hWJMSCs(hWJMSC-Cs)的结果与未分化的细胞相似,只是MHC-II和共刺激因子的表达略有升高。此外,我们通过细胞因子抗体阵列检测了hWJMSC的细胞因子谱,并通过Western blot证实了免疫抑制相关分子,HGF,VEGF,TGF和IL-10的阳性表达。此外,为了研究细胞的体内免疫应答,将hWJMSCs-支架构建体植入兔和大鼠中,结果表明hWJMSCs没有引起动物的免疫排斥。它们在成体和胚胎干细胞之间的中间状态使其成为重编程为多能状态的理想候选者。有必要进行其他研究来阐明hWJMSC在软骨和其他组织再生以及基于细胞的疗法中的潜力。

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