Bone marrow stromal cell transplantation mitigates radiation-induced gastrointestinal syndrome in mice.
Bone marrow stromal cell transplantation mitigates radiation-induced gastrointestinal syndrome in mice.
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DOI：
10.1371/journal.pone.0024072
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发表时间：
2011
期刊：
影响因子：
3.7
通讯作者：
Guha C
中科院分区：
文献类型：
--
作者：
Saha S;Bhanja P;Kabarriti R;Liu L;Alfieri AA;Guha C
核事故和恐怖主义是造成大规模伤亡的严重威胁。虽然骨髓移植可能减轻造血综合征，但目前还没有批准的医学对策来减轻辐射诱导的胃肠道综合征（RIGS），这是由对肠干细胞（ISC）和隐窝基质细胞的直接杀细胞作用引起的。我们研究了骨髓来源的贴壁基质细胞移植（BMSCT）是否可以恢复辐射肠干细胞的生态位，减轻辐射诱导的胃肠道综合征。在致死全身照射（10.4戈伊）或腹部照射（16-20戈伊）后24和72小时，在间充质基础培养基中培养自体骨髓，收获贴壁细胞用于移植到C57 B16小鼠。间充质、内皮和髓样细胞群通过流式细胞术表征。通过组织病理学和木糖吸收实验观察肠腺再生和吸收功能。与照射对照组的100%死亡率相比，BMSCT减轻了RIGS，并在18戈伊腹部照射或10.4戈伊全身照射后挽救了小鼠的辐射致死率，25天后存活率为100%（分别为p<0.0007和p<0.0009）。骨髓和非骨髓成分的移植未能提高存活率。BMASCT诱导ISC再生、ISC生态位恢复和木糖吸收。血清中肠辐射防护因子如R-Spondin 1、KGF、PDGF和FGF 2以及抗炎细胞因子水平升高，而炎性细胞因子水平下调。通过静脉内移植骨髓来源的基质细胞，包括间充质细胞、内皮细胞和巨噬细胞群，可以减轻高剂量照射后的致死性肠损伤。BMASCT增加肠道生长因子的血液水平，并诱导受照射的宿主ISC生态位的再生，从而提供了一个平台，以发现潜在的辐射缓解剂和保护剂，用于急性辐射综合征和腹部恶性肿瘤的化学-放射治疗。
Nuclear accidents and terrorism presents a serious threat for mass casualty. While bone-marrow transplantation might mitigate hematopoietic syndrome, currently there are no approved medical countermeasures to alleviate radiation-induced gastrointestinal syndrome (RIGS), resulting from direct cytocidal effects on intestinal stem cells (ISC) and crypt stromal cells. We examined whether bone marrow-derived adherent stromal cell transplantation (BMSCT) could restitute irradiated intestinal stem cells niche and mitigate radiation-induced gastrointestinal syndrome. Autologous bone marrow was cultured in mesenchymal basal medium and adherent cells were harvested for transplantation to C57Bl6 mice, 24 and 72 hours after lethal whole body irradiation (10.4 Gy) or abdominal irradiation (16–20 Gy) in a single fraction. Mesenchymal, endothelial and myeloid population were characterized by flow cytometry. Intestinal crypt regeneration and absorptive function was assessed by histopathology and xylose absorption assay, respectively. In contrast to 100% mortality in irradiated controls, BMSCT mitigated RIGS and rescued mice from radiation lethality after 18 Gy of abdominal irradiation or 10.4 Gy whole body irradiation with 100% survival (p<0.0007 and p<0.0009 respectively) beyond 25 days. Transplantation of enriched myeloid and non-myeloid fractions failed to improve survival. BMASCT induced ISC regeneration, restitution of the ISC niche and xylose absorption. Serum levels of intestinal radioprotective factors, such as, R-Spondin1, KGF, PDGF and FGF2, and anti-inflammatory cytokines were elevated, while inflammatory cytokines were down regulated. Mitigation of lethal intestinal injury, following high doses of irradiation, can be achieved by intravenous transplantation of marrow-derived stromal cells, including mesenchymal, endothelial and macrophage cell population. BMASCT increases blood levels of intestinal growth factors and induces regeneration of the irradiated host ISC niche, thus providing a platform to discover potential radiation mitigators and protectors for acute radiation syndromes and chemo-radiation therapy of abdominal malignancies.
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影响因子：
64.5
作者：
Goessling W;North TE;Loewer S;Lord AM;Lee S;Stoick-Cooper CL;Weidinger G;Puder M;Daley GQ;Moon RT;Zon LI
通讯作者：
Zon LI
DOI：
10.1152/ajpgi.00453.2007
发表时间：
2008-03-01
影响因子：
4.5
作者：
Ghia, Jean-Eric;Galeazzi, Francesca;Collins, Stephen
通讯作者：
Collins, Stephen
影响因子：
82.9
作者：
通讯作者：
--
DOI：
10.1073/pnas.0405979102
发表时间：
2005-01-04
影响因子：
11.1
作者：
Pull, SL;Doherty, JM;Stappenbeck, TS
通讯作者：
Stappenbeck, TS
影响因子：
82.9
作者：
Okamoto, R;Yajima, T;Watanabe, M
通讯作者：
Watanabe, M