The evaluation of the safety and efficacy of intravenously administered allogeneic multilineage-differentiating stress-enduring cells in a swine hepatectomy model
The evaluation of the safety and efficacy of intravenously administered allogeneic multilineage-differentiating stress-enduring cells in a swine hepatectomy model
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DOI：
10.1007/s00595-020-02117-0
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发表时间：
2020-09-11
期刊：
影响因子：
2.5
通讯作者：
Unno, Michiaki
中科院分区：
文献类型：
--
作者：
Iseki, Masahiro;Mizuma, Masamichi;Unno, Michiaki
前言多系分化应激耐受(MUSE)细胞是存在于骨髓中的非肿瘤内源性多能样细胞，通过自发分化为组织构成细胞，替代受损/凋亡的细胞，发挥组织修复作用。肝切除术后肝功能衰竭(PHLF)是一种潜在的致命并发症。本研究的主要目的是评价同种异体小鼠细胞经门静脉给药在猪PHLF模型中的安全性和有效性。方法取猪骨髓间充质干细胞(MSCs)作为SSEA-3(+)细胞，对其进行鉴定。然后，将1×10(7)的同种异体小鼠细胞、同种异体骨髓间充质干细胞和赋形剂经门静脉注入70%肝切除猪模型。结果猪MUSE细胞具有与以往报道的人类MUSE细胞相似的特性。与MSC组和赋形剂组相比，MUSE组在高胆红素血症的控制(P=0.04)、凝血酶原国际正常化比率(P=0.05)和局灶性坏死的抑制(P=0.04)方面显示出特异性的细胞归巢入肝。整合后的小鼠细胞自发分化为肝细胞标记物阳性细胞。结论同种异体小鼠细胞移植对70%肝切除猪模型有一定的修复作用和功能恢复作用，有助于PHLF的治疗。
Introduction Multilineage-differentiating stress-enduring (Muse) cells are non-tumorigenic endogenous pluripotent-like cells residing in the bone marrow that exert a tissue reparative effect by replacing damaged/apoptotic cells through spontaneous differentiation into tissue-constituent cells. Post-hepatectomy liver failure (PHLF) is a potentially fatal complication. The main purpose of this study was to evaluate the safety and efficiency of allogeneic Muse cell administration via the portal vein in a swine model of PHLF. Methods Swine Muse cells, collected from swine bone marrow-mesenchymal stem cells (MSCs) as SSEA-3(+) cells, were examined for their characteristics. Then, 1 x 10(7)allogeneic-Muse cells and allogeneic-MSCs and vehicle were injected via the portal vein in a 70% hepatectomy swine model. Results Swine Muse cells exhibited characteristics comparable to previously reported human Muse cells. Compared to the MSC and vehicle groups, the Muse group showed specific homing of the administered cells into the liver, resulting in improvements in the control of hyperbilirubinemia (P = 0.04), prothrombin international normalized ratio (P = 0.05), and suppression of focal necrosis (P = 0.04). Integrated Muse cells differentiated spontaneously into hepatocyte marker-positive cells. Conclusions Allogeneic Muse cell administration may provide a reparative effect and functional recovery in a 70% hepatectomy swine model and thus may contribute to the treatment of PHLF.