决定异体 CAR T 细胞排斥与扩增的细胞和分子机制
Cellular and molecular mechanisms determining allogeneic CAR T cell rejection and expansion.
我们评估了11例接受单一批次cemacabtagene ansegedleucel(cema-cel)治疗的大B细胞淋巴瘤患者,cemacabtagene ansegedleucel是一种异体抗CD19 CAR T产品。
英文原题:Umbilical cord-derived mesenchymal stem cells cultured in the MCL medium for aplastic anemia therapy.
MCL 中的 MSC 在支持造血和调节免疫方面具有优势,并具有有效治疗 AA 的潜力。
背景:间充质干细胞(MSC)是一类具有自我更新和多向分化潜能的成体干细胞,可能用于治疗再生障碍性贫血(AA)。方法:将脐带来源 MSC 分别培养于三种培养基:Mesencult-XF、MCL 和 StemPro MSC SFM CTS。采用 ELISA 检测 HGF、PGE2、ANG-1、TGF-β1、IFN-γ 和 TNF-α。通过放疗后输注淋巴细胞建立 AA 小鼠模型。不同处理后,每周检测常规血液指标、VEGF 和 Treg。第 28 天处死所有小鼠,并对股骨进行 HE 染色。结果:脐带来源 MSC 在三种培养基中培养后均符合 MSC 的一般特征。Mesencult-XF 和 MCL 培养的 MSC 分泌 HGF 多于 StemPro MSC SFM CTS 培养的 MSC;MCL 培养的细胞中 ANG-1 和 TGF-β1 水平高于 Mesencult-XF 和 StemPro MSC SFM CTS;MCL 和 StemPro MSC SFM CTS 中 PGE2 水平均高于 Mesencult-XF。与 Mesencult-XF 相比,MCL 和 StemPro MSC SFM CTS 培养的 MSC 对 IFN-γ 和 TNF-α 的抑制作用更强。AA 组外周血细胞处于较低水平,而 MSC 组恢复较快。MSC 组 Treg 比例和 VEGF 水平均高于 AA 组。输注 MSC 后,骨髓(BM)明显恢复。结论:MCL 培养的 MSC 在支持造血和调节免疫方面具有优势,并具有有效治疗 AA 的潜力。
BACKGROUND: Mesenchymal stem cells (MSCs) are a class of adult stem cells with self-renewal and multidirectional differentiation potential that may be a treatment for aplastic anemia (AA). METHOD: Umbilical cord-derived MSCs were cultured in three media (Mesencult-XF, MCL, and StemPro MSC SFM CTS). HGF, PGE2, ANG-1, TGF- 1, IFN- , and TNF- were detected using ELISA. The AA mouse model was built via post-irradiation lymphocyte infusion. After different treatments, routine blood, VEGF, and Tregs were detected every week. On day 28, all mice were killed, and their femurs were stained with HE. RESULTS: Umbilical cord-derived MSCs cultured in the three media all conformed to the general characteristics of MSCs. HGF secreted by MSCs in the Mesencult-XF, and MCL was greater than that in the StemPro MSC SFM CTS; ANG-1 and TGF- 1 in the MCL were more than that in Mesencult-XF and StemPro MSC SFM CTS; PGE2 in the MCL and StemPro MSC SFM CTS was more than that in the Mesencult-XF. MSCs in the MCL and StemPro MSC SFM CTS inhibited IFN- and TNF- more than those in the Mesencult-XF. The peripheral blood cell in the AA groups was at a low level while that in the MSC group recovered rapidly. The Treg ratio and VEGF level in the MSC group were higher than those in the AA group. The bone marrow (BM) recovered significantly after MSC infusion. CONCLUSION: MSCs in the MCL were advantageous in supporting hematopoiesis and modulating immunity and had the potential for effective treatment of AA.
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