Transplantation of Donor-Recipient Chimeric Cells Restores Peripheral Blood Cell Populations and Increases Survival after Total Body Irradiation-Induced Injury in a Rat Experimental Model.

IF 2.9 4区 医学 Q3 IMMUNOLOGY
Archivum Immunologiae et Therapiae Experimentalis Pub Date : 2024-05-23 eCollection Date: 2024-01-01 DOI:10.2478/aite-2024-0009
Maria Siemionow, Małgorzata Cyran, Katarzyna Stawarz, Lucile Chambily, Krzysztof Kusza
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引用次数: 0

Abstract

Current therapies for acute radiation syndrome (ARS) involve bone marrow transplantation (BMT), leading to graft-versus-host disease (GvHD). To address this challenge, we have developed a novel donor-recipient chimeric cell (DRCC) therapy to increase survival and prevent GvHD following total body irradiation (TBI)-induced hematopoietic injury without the need for immunosuppression. In this study, 20 Lewis rats were exposed to 7 Gy TBI to induce ARS, and we assessed the efficacy of various cellular therapies following systemic intraosseous administration. Twenty Lewis rats were randomly divided into four experimental groups (n = 5/group): saline control, allogeneic bone marrow transplantation (alloBMT), DRCC, and alloBMT + DRCC. DRCC were created by polyethylene glycol-mediated fusion of bone marrow cells from 24 ACI (RT1a) and 24 Lewis (RT11) rat donors. Fusion feasibility was confirmed by flow cytometry and confocal microscopy. The impact of different therapies on post-irradiation peripheral blood cell recovery was evaluated through complete blood count, while GvHD signs were monitored clinically and histopathologically. The chimeric state of DRCC was confirmed. Post-alloBMT mortality was 60%, whereas DRCC and alloBMT + DRCC therapies achieved 100% survival. DRCC therapy also led to the highest white blood cell counts and minimal GvHD changes in kidney and skin samples, in contrast to alloBMT treatment. In this study, transplantation of DRCC promoted the recovery of peripheral blood cell populations after TBI without the development of GVHD. This study introduces a novel and promising DRCC-based bridging therapy for treating ARS and extending survival without GvHD.

在大鼠实验模型中,移植供体-受体嵌合细胞可恢复全身辐照损伤后的外周血细胞群并提高存活率。
目前治疗急性放射综合征(ARS)的方法包括骨髓移植(BMT),这会导致移植物抗宿主疾病(GvHD)。为了应对这一挑战,我们开发了一种新型供体-受体嵌合细胞(DRCC)疗法,以提高存活率并预防全身照射(TBI)诱导的造血损伤后的移植物抗宿主疾病(GvHD),而无需免疫抑制。在这项研究中,20 只 Lewis 大鼠暴露于 7 Gy TBI 以诱导 ARS,我们评估了全身骨内给药后各种细胞疗法的疗效。20 只 Lewis 大鼠被随机分为四个实验组(n = 5/组):生理盐水对照组、同种异体骨髓移植(alloBMT)组、DRCC 组和 alloBMT + DRCC 组。DRCC 是通过聚乙二醇介导融合 24 名 ACI(RT1a)和 24 名 Lewis(RT11)大鼠供体的骨髓细胞而产生的。流式细胞术和共聚焦显微镜证实了融合的可行性。通过全血细胞计数评估了不同疗法对辐照后外周血细胞恢复的影响,同时通过临床和组织病理学监测了GvHD迹象。DRCC的嵌合状态得到了证实。同种异体移植后的死亡率为 60%,而 DRCC 和同种异体移植 + DRCC疗法的存活率为 100%。与同种异体移植疗法相比,DRCC疗法的白细胞计数最高,肾脏和皮肤样本的GvHD变化最小。在这项研究中,DRCC移植促进了创伤性脑损伤后外周血细胞群的恢复,且未出现GVHD。这项研究介绍了一种新颖且前景广阔的基于DRCC的桥接疗法,可用于治疗ARS并延长存活期,且不会出现GVHD。
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来源期刊
CiteScore
5.90
自引率
0.00%
发文量
26
审稿时长
>12 weeks
期刊介绍: Archivum Immunologiae et Therapiae Experimentalis (AITE), founded in 1953 by Ludwik Hirszfeld, is a bimonthly, multidisciplinary journal. It publishes reviews and full original papers dealing with immunology, experimental therapy, immunogenetics, transplantation, microbiology, immunochemistry and ethics in science.
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