体外冷冻大鼠骨髓源性多能间充质间质细胞修复大鼠辐射损伤的作用

Q4 Medicine
N. Uzlenkova, N. Skorobogatova, A. Kryvko, M. Krasnoselsky
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引用次数: 1

摘要

目前,应用多能间充质基质细胞(MSCs)作为辐射损伤的细胞治疗越来越受到关注,因为目前的医疗管理还远远不能令人满意。本研究的目的是检验冷冻保存的离体扩增骨髓间充质干细胞(rBM-MSCs)在大鼠全身和局部辐射暴露模型上修复辐射损伤的疗效。材料和方法。间充质干细胞来源于4个月龄未经辐照的雌性白化大鼠的骨髓,短期离体扩增两代,并在二甲基亚砜冷冻保护下冷冻保存,在-70℃下低温保存6-12个月。在体内实验中将来自每批rBM-MSCs培养物的冷冻保存样品移植到大鼠之前,测试其生存能力和功能特征。通过剂量为5.5Gy(TBI 5.5)和7.0Gy(TBI 7.0)的全身照射(TBI)和剂量为50Gy的右髋皮肤局部照射来模拟大鼠的急性辐射损伤。冷冻保存的rBM-MSCs(1.5•106和0.5•106细胞/动物)在TBI后24小时内静脉内移植,并在大腿照射后第15天和第21天局部注射(1.5•106/动物两次)。通过存活率和血液学研究以及辐照皮肤伤口愈合试验来评估冷冻保存的rBM-MSCs的疗效。后果冷冻保存的离体扩增rBM-MSC的特征在于具有约80%的细胞活力的高水平的功能活性、包括至少8.5%的集落形成MSC和具有在TBI 5.5大鼠中成脂和成骨分化能力的MSC,冷冻保存的移植rBM-MSCs(1.5106个细胞/只)通过在第2天增加3.7倍的白细胞数量来防止辐射损伤的第一个关键日子的急性白细胞减少,并通过在第22天增加BM细胞数量和血小板计数来促进血液病的更完全恢复,这导致总生存率的增加,最高可达100%,体重恢复。在TBI 7.0大鼠中,较低剂量的rBM-MSCs(0.5•106个细胞/只)在总体恢复方面更有效,并将总生存时间延长了6天。根据评分和伤口大小测定的结果,局部注射rBM-MSCs(两次1.5•106个细胞/动物)降低了放射性皮肤伤口的严重程度,并促进了伤口的愈合。结论本研究证实,冷冻保存的离体扩增rBM-MSCs在功能上完全可用于实验性辐射损伤的大鼠模型的治疗,并且对辐射暴露后的造血系统和严重皮肤伤口的恢复有效。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
The efficacy of cryopreserved ex vivo expanded rat bone marrow-derived multipotent mesenchymal stromal cells in the repair of radiation injuries in rats
At present, applying multipotent mesenchymal stromal cells (MSCs) as cell therapy for radiation damages have gained increasing attention since current medical management remains far from satisfactory. The aim of the study is to examine the efficacy of cryopreserved ex vivo expanded bone marrow-derived MSCs (rBM-MSCs) to the repair of radiation injuries on rat models of total and local radiation exposure. Materials and methods. The MSCs were derived from bone marrow of non-irradiated female albino rats aged 4 months, short-term ex vivo expanded for two passages and cryopreserved under dimethyl sulfoxide cryoprotection for low temperature storage at -70 oC for 6-12 months. The cryopreserved samples from each batch of rBM-MSCs culture were tested for the viability and functional characteristics before being transplanted to rats in experiments in vivo. The acute radiation damages in rats were modeled by total body irradiation (TBI) at doses of 5.5 Gy (TBI 5.5) and 7.0 Gy (TBI 7.0) and locally irradiated in the right hip skin at a dose of 50 Gy. The cryopreserved rBM-MSCs (1.5•106 and 0.5•106 cells/animal) were intravenously transplanted within 24 h following TBI and locally injected (twice 1.5•106 Cells/animals) on days 15 and 21 following thigh irradiation. The efficacy of cryopreserved rBM-MSCs was assessed by survival and hematological study as well as the irradiated skin wound healing assay. Results. The cryopreserved ex vivo expanded rBM-MSCs were characterized by high level of functional activity with cell viability about 80 %, include at least 8.5 % of the colony forming MSCs and MSCs with ability to adipogenic and osteogenic differentiation In TBI 5.5 rats, cryopreserved transplanted rBM-MSCs (1.5·106 cells/animal) prevented acute leukopenia in the first critical days of the radiation injury by increasing the number of leukocytes by 3.7 times on day 2 and contributed to a more complete recovery of hematological disorders by increasing the BM cells number and platelet count on day 22, which led to the increase of the increase of overall survival up to 100 % with a regain of body weight. In TBI 7.0 rats, the lower transplanted dose of rBM-MSCs (0.5•106 cells/animal) was more effective in terms of general recovery and extended the overall survival time for 6 days. The locally injected rBM-MSCs (twice 1.5•106 cells/animals) reduced the severity and promoted the healing of radiation skin wounds according to the results of scoring and wound size assay. Conclusion. The present study confirms that the cryopreserved ex vivo expanded rBM-MSCs were functionally complete for the therapeutic use on rat models of experimental radiation damage and were effective for the recovery of hematopoietic system and severe skin wound after radiation exposure.
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来源期刊
Cell and Organ Transplantology
Cell and Organ Transplantology Medicine-Transplantation
CiteScore
0.40
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