研究动态
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间充质基质细胞治疗的时机决定了其在大鼠肺移植模型中的免疫抑制作用。

Timing of Mesenchymal Stromal Cell Therapy Defines its Immunosuppressive Effects in a Rat Lung Transplantation Model.

发表日期:2023
作者: Yukinori Tanoue, Tomoshi Tsuchiya, Takuro Miyazaki, Mayumi Iwatake, Hironosuke Watanabe, Hiroshi Yukawa, Kazuhide Sato, Go Hatachi, Koichiro Shimoyama, Keitaro Matsumoto, Ryoichiro Doi, Koichi Tomoshige, Takeshi Nagayasu
来源: Stem Cell Research & Therapy

摘要:

正在研究使用间充质基质细胞(MSC)的细胞疗法的免疫抑制作用。在器官移植中,移植器官和其他器官中积累的间充质干细胞的数量可能会因给药时间的不同而有所不同,这可能会影响其免疫抑制效果。在体外,脂肪源性间充质干细胞(ADMSC)在细胞间接触条件下抑制淋巴细胞活化。然而,在体内,ADMSCs在移植器官或次级淋巴器官中积累是否更有效尚存在争议。在此,我们的目的是研究ADMSC的给药时机是否影响其在大鼠肺移植模型中的免疫抑制能力。在移植研究中,大鼠肺移植后每24小时肌内注射常用剂量一半的他克莫司(0.5 mg/kg)。 ADMSCs (1 × 106) 在移植前 (PreTx) 或移植后 (PostTx) 通过颈静脉给药。使用量子点进行细胞追踪。 ADMSCs 主要积聚在肺和肝中; PreTx 组移植肺中分布的 ADMSC 数量少于 PostTx 组。 ADMSC 给药组的排斥率非常低,尤其是 PostTx 组。 PreTx 组的血清肿瘤坏死因子-α (TNF-α)、干扰素-γ 和白细胞介素 (IL)-6 水平比 PostTx 组显示出更大的下降趋势。移植后10天移植肺中调节性T细胞的比例PostTx组高于PreTx组。 PostTx 给药比 PreTx 给药更好地抑制排斥反应,这可能是由于移植肺中积累的 ADMSC 诱导调节性 T 细胞所致,这表明与心脏或肾移植中的机制不同,PreTx 给药比 PostTx 给药更有效。这些结果可能有助于建立在肺移植中使用间充质干细胞的细胞疗法。
Cell therapy using mesenchymal stromal cells (MSCs) is being studied for its immunosuppressive effects. In organ transplantation, the amount of MSCs that accumulate in transplanted organs and other organs may differ depending on administration timing, which may impact their immunosuppressive effects. In vitro, adipose-derived mesenchymal stem cells (ADMSCs) suppress lymphocyte activation under cell-to-cell contact conditions. However, in vivo, it is controversial whether ADMSCs are more effective in accumulating in transplanted organs or in secondary lymphoid organs. Herein, we aimed to investigate whether the timing of ADMSC administration affects its immunosuppression ability in a rat lung transplantation model. In the transplantation study, rats were intramuscularly administered half the usual dose of tacrolimus (0.5 mg/kg) every 24 h after lung transplantation. ADMSCs (1 × 106) were administered via the jugular vein before (PreTx) or after (PostTx) transplantation. Cell tracking using quantum dots was performed. ADMSCs accumulated predominantly in the lung and liver; fewer ADMSCs were distributed in the grafted lung in the PreTx group than in the PostTx group. The rejection rate was remarkably low in the ADMSC-administered groups, particularly in the PostTx group. Serum tumor necrosis factor-α (TNF-α), interferon-γ, and interleukin (IL)-6 levels showed a greater tendency to decrease in the PreTx group than in the PostTx group. The proportion of regulatory T cells in the grafted lung 10 days after transplantation was higher in the PostTx group than in the PreTx group. PostTx administration suppresses rejection better than PreTx administration, possibly due to regulatory T cell induction by ADMSCs accumulated in the transplanted lungs, suggesting a mechanism different from that in heart or kidney transplantation that PreTx administration is more effective than PostTx administration. These results could help establish cell therapy using MSCs in lung transplantation.