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优化脂肪组织来源的间充质基质细胞移植用于辐照后骨髓再填充

Optimization of adipose tissue-derived mesenchymal stromal cells transplantation for bone marrow repopulation following irradiation.

作者信息

Kim Min-Jung, Moon Won, Heo Jeonghoon, Lim Sangwook, Lee Seung-Hyun, Jeong Jee-Yeong, Lee Sang Joon

机构信息

Department of Biochemistry, Cancer Research Institute Kosin University College of Medicine, Seo-gu 49267, Busan, South Korea.

Department of Internal Medicine, Kosin University College of Medicine, Seo-gu 49267, Busan, South Korea.

出版信息

World J Stem Cells. 2022 Mar 26;14(3):245-263. doi: 10.4252/wjsc.v14.i3.245.

Abstract

BACKGROUND

Bone marrow (BM) suppression is one of the most common side effects of radiotherapy and the primary cause of death following exposure to irradiation. Despite concerted efforts, there is no definitive treatment method available. Recent studies have reported using mesenchymal stromal cells (MSCs), but their therapeutic effects are contested.

AIM

We administered and examined the effects of various amounts of adipose-derived MSCs (ADSCs) in mice with radiation-induced BM suppression.

METHODS

Mice were divided into three groups: Normal control group, irradiated (RT) group, and stem cell-treated group following whole-body irradiation (WBI). Mouse ADSCs (mADSCs) were transplanted into the peritoneal cavity either once or three times at 5 × 10 cells/200 μL. The white blood cell count and the levels of, plasma cytokines, BM mRNA, and BM surface markers were compared between the three groups. Human BM-derived CD34 hematopoietic progenitor cells were co-cultured with human ADSCs (hADSCs) or incubated in the presence of hADSCs conditioned media to investigate the effect on human cells .

RESULTS

The survival rate of mice that received one transplant of mADSCs was higher than that of mice that received three transplants. Multiple transplantations of ADSCs delayed the repopulation of BM hematopoietic stem cells. Anti-inflammatory effects and M2 polarization by intraperitoneal ADSCs might suppress erythropoiesis and induce myelopoiesis in sub-lethally RT mice.

CONCLUSION

The results suggested that an optimal amount of MSCs could improve survival rates post-WBI.

摘要

背景

骨髓抑制是放疗最常见的副作用之一,也是辐射暴露后死亡的主要原因。尽管人们共同努力,但目前尚无确切的治疗方法。最近的研究报道了使用间充质基质细胞(MSC),但其治疗效果存在争议。

目的

我们对辐射诱导的骨髓抑制小鼠给予不同数量的脂肪来源间充质干细胞(ADSC)并检测其效果。

方法

将小鼠分为三组:正常对照组、全身照射(WBI)后的照射(RT)组和干细胞治疗组。将小鼠ADSC(mADSC)以5×10个细胞/200μL的剂量腹腔注射一次或三次。比较三组之间的白细胞计数、血浆细胞因子水平、骨髓mRNA和骨髓表面标志物。将人骨髓来源的CD34造血祖细胞与人ADSC(hADSC)共培养,或在hADSC条件培养基存在下孵育,以研究对人细胞的影响。

结果

接受一次mADSC移植的小鼠存活率高于接受三次移植的小鼠。ADSC的多次移植延迟了骨髓造血干细胞的再填充。腹腔内ADSC的抗炎作用和M2极化可能会抑制亚致死性放疗小鼠的红细胞生成并诱导粒细胞生成。

结论

结果表明,适量的MSC可以提高WBI后的存活率。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b6e1/8968216/5658a1e7fa30/WJSC-14-245-g001.jpg

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