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Abstract：
BACKGROUND: Haematopoietic stem cell (HSC) infusion has demonstrated short-term improvement in liver functions in patients with chronic liver disease. The combination of HSC with mesenchymal stem cells (MSCs), which has an immunomodulatory effect, may augment the effects and enhance the duration of improvements on liver functions. The aim of the present study was to assess the safety of infusing the combination of autologous HSCs and MSCs in decompensated liver cirrhosis.
METHODS: In phase I of the study, in vitro assessment was performed to observe the effect of coculturing MSCs with HSCs on their viability and cytokine profiles. Phase II of the study was to assess the safety of combination of stem cell infusions. Bone marrow (50 ml) was aspirated for MSC isolation and expansion using standard protocol. Patients received subcutaneous doses (n = 5) of granulocyte colony-stimulating factor (G-CSF) for stem cell mobilization followed by leukapheresis for harvesting HSCs using CliniMacs. HSCs and MSCs were infused through the hepatic artery under fluoroscopic guidance and were monitored for any adverse effects.
RESULTS: In vitro studies revealed 94% viable HSCs in coculture similar to monoculture. HSCs released only interleukin (IL)-8, whereas MSCs secreted IL-8 and IL-6 in monocultures, and both IL-8 and IL-6 were secreted in coculture. G-CSF administration- and bone marrow aspiration-related complications were not observed. Infusion of the cells through the hepatic artery was safe, and no postprocedural complications were noted.
CONCLUSIONS: The combination of autologous HSC and MSC infusion is a safe procedure in patients with decompensated liver cirrhosis, and the outcomes needed to be assessed in larger studies.
BACKGROUND: NCT04243681.
METHODS: In phase I of the study, in vitro assessment was performed to observe the effect of coculturing MSCs with HSCs on their viability and cytokine profiles. Phase II of the study was to assess the safety of combination of stem cell infusions. Bone marrow (50 ml) was aspirated for MSC isolation and expansion using standard protocol. Patients received subcutaneous doses (n = 5) of granulocyte colony-stimulating factor (G-CSF) for stem cell mobilization followed by leukapheresis for harvesting HSCs using CliniMacs. HSCs and MSCs were infused through the hepatic artery under fluoroscopic guidance and were monitored for any adverse effects.
RESULTS: In vitro studies revealed 94% viable HSCs in coculture similar to monoculture. HSCs released only interleukin (IL)-8, whereas MSCs secreted IL-8 and IL-6 in monocultures, and both IL-8 and IL-6 were secreted in coculture. G-CSF administration- and bone marrow aspiration-related complications were not observed. Infusion of the cells through the hepatic artery was safe, and no postprocedural complications were noted.
CONCLUSIONS: The combination of autologous HSC and MSC infusion is a safe procedure in patients with decompensated liver cirrhosis, and the outcomes needed to be assessed in larger studies.
BACKGROUND: NCT04243681.
摘要：
背景：造血干细胞（HSC）输注已证明慢性肝病患者的肝功能短期改善。HSC与间充质干细胞（MSCs）的组合，具有免疫调节作用，可能会增强效果并延长肝功能改善的持续时间。本研究的目的是评估在失代偿期肝硬化中输注自体HSCs和MSCs组合的安全性。
方法：在研究的第一阶段，进行体外评估以观察共培养MSC与HSC对其活力和细胞因子谱的影响。研究的第二阶段是评估干细胞输注组合的安全性。使用标准方案抽吸骨髓(50ml)用于MSC分离和扩增。患者接受皮下剂量（n=5）的粒细胞集落刺激因子（G-CSF）用于干细胞动员，然后使用CliniMac进行白细胞去除术以收获HSC。在荧光透视引导下通过肝动脉输注HSC和MSC,并监测任何不良反应。
结果:体外研究显示,在类似于单一培养的共培养中94%的活HSC。HSC仅释放白细胞介素（IL）-8，而MSC在单一培养中分泌IL-8和IL-6，IL-8和IL-6在共培养中均分泌。未观察到G-CSF给药和骨髓抽吸相关并发症。通过肝动脉输注细胞是安全的，未发现术后并发症.
结论：在失代偿期肝硬化患者中，自体HSC和MSC联合输注是一种安全的方法，结果需要在更大的研究中进行评估.
背景：NCT04243681。
方法：在研究的第一阶段，进行体外评估以观察共培养MSC与HSC对其活力和细胞因子谱的影响。研究的第二阶段是评估干细胞输注组合的安全性。使用标准方案抽吸骨髓(50ml)用于MSC分离和扩增。患者接受皮下剂量（n=5）的粒细胞集落刺激因子（G-CSF）用于干细胞动员，然后使用CliniMac进行白细胞去除术以收获HSC。在荧光透视引导下通过肝动脉输注HSC和MSC,并监测任何不良反应。
结果:体外研究显示,在类似于单一培养的共培养中94%的活HSC。HSC仅释放白细胞介素（IL）-8，而MSC在单一培养中分泌IL-8和IL-6，IL-8和IL-6在共培养中均分泌。未观察到G-CSF给药和骨髓抽吸相关并发症。通过肝动脉输注细胞是安全的，未发现术后并发症.
结论：在失代偿期肝硬化患者中，自体HSC和MSC联合输注是一种安全的方法，结果需要在更大的研究中进行评估.
背景：NCT04243681。
