Inhibitory Effects of iPSC-MSCs and Their Extracellular Vesicles on the Onset of Sialadenitis in a Mouse Model of Sjögren's Syndrome.
Inhibitory Effects of iPSC-MSCs and Their Extracellular Vesicles on the Onset of Sialadenitis in a Mouse Model of Sjögren's Syndrome.
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DOI：
10.1155/2018/2092315
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发表时间：
2018
影响因子：
4.3
通讯作者：
Liu F
中科院分区：
文献类型：
--
作者：
Hai B;Shigemoto-Kuroda T;Zhao Q;Lee RH;Liu F
干燥综合征（SS）是一种主要影响唾液腺和泪腺的慢性自身免疫性疾病，目前尚无有效的治疗方法。在小鼠模型和一项小型临床试验中，系统性输注从骨髓 (BM) 等组织分离的同种异体间充质干细胞 (MSC) 可缓解 SS，但这种 MSC 疗法的进一步研究和应用受到有限的扩展性、显着的供体变异和组织源性 MSC 的安全性问题的阻碍。为了规避这些问题，我们使用优化的方案从人类 iPSC 中衍生出 MSC，该方案可以轻松扩大规模以产生大量标准化 MSC。我们的 iPSC-MSC 以与 BM-MSC 相同的方式抑制 SS 的 NOD 小鼠模型中淋巴细胞浸润到唾液腺的发生。细胞外囊泡（EV）以与其原始细胞相同的方式携带生物活性分子，并且比用于治疗的细胞更稳定并且被认为更安全。我们发现，源自 BM-MSC 和 iPSC-MSC 的 EV 在体外抑制了免疫细胞的活化和 SS 进展所必需的促炎症因子的表达，并且与输注 BM-MSC 和 iPSC-MSC 相同，在疾病前期输注 iPSC-MSC EV 降低了唾液腺中的淋巴细胞浸润和血清自身抗体水平。这些数据表明 iPSC-MSC EV 有可能在唾液腺炎发作前预防 SS 的进展。
No effective treatment for Sjögren's syndrome (SS), a chronic autoimmune disease affecting mainly salivary and lacrimal glands, is available now. Systemic infusion of allogeneic mesenchymal stem cells (MSCs) isolated from tissues such as bone marrow (BM) alleviated SS in mouse models and a small clinical trial, but further research and application of this MSC therapy were hindered by limited expandability, significant donor variations, and safety concerns of tissue-derived MSCs. To circumvent these issues, we derived MSCs from human iPSCs using an optimized protocol that can be easily scaled up to produce a huge amount of standardized MSCs. Our iPSC-MSCs inhibited the onset of lymphocyte infiltration into salivary glands in the NOD mouse model of SS in the same way as BM-MSCs. Extracellular vesicles (EVs) carry bioactive molecules in the same way as their originating cells and are more stable and considered much safer than cells for therapies. We found that EVs derived from BM-MSCs and iPSC-MSCs suppressed activation of immune cells and expression of proinflammation factors essential for SS progression in vitro and that infusion of iPSC-MSC EVs at the predisease stage decreased the lymphocyte infiltration in salivary glands and serum autoantibody levels in the same way as infusion of BM-MSCs and iPSC-MSCs. These data suggested that iPSC-MSC EVs have the potential to prevent the progression of SS before the onset of sialadenitis.
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影响因子：
3.7
作者：
Jin, Jun-O;Shinohara, Yoshinori;Yu, Qing
通讯作者：
Yu, Qing
影响因子：
3.3
作者：
Budoni, Manuela;Fierabracci, Alessandra;Muraca, Maurizio
通讯作者：
Muraca, Maurizio
DOI：
10.1073/pnas.1522905113
发表时间：
2016-01-05
影响因子：
11.1
作者：
Ko, Jung Hwa;Lee, Hyun Ju;Oh, Joo Youn
通讯作者：
Oh, Joo Youn
影响因子：
4.6
作者：
Di Trapani M;Bassi G;Midolo M;Gatti A;Kamga PT;Cassaro A;Carusone R;Adamo A;Krampera M
通讯作者：
Krampera M
影响因子：
3.7
作者：
Misuno K;Tran SD;Khalili S;Huang J;Liu Y;Hu S
通讯作者：
Hu S