Mesenchymal stem cell therapy stimulates endogenous host progenitor cells to improve colonic epithelial regeneration.
Mesenchymal stem cell therapy stimulates endogenous host progenitor cells to improve colonic epithelial regeneration.
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DOI：
10.1371/journal.pone.0070170
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发表时间：
2013
期刊：
影响因子：
3.7
通讯作者：
Mathieu N
中科院分区：
文献类型：
--
作者：
Sémont A;Demarquay C;Bessout R;Durand C;Benderitter M;Mathieu N
接受盆腔放疗的患者可能会因胃肠道改变而产生严重的慢性并发症。缺乏治愈性治疗突出了新的和有效的治疗策略的重要性。因此，我们测试了间充质干细胞（MSC）治疗的治疗效益，并提出了作用的分子机制。在组织学上类似于在患者中观察到的放射诱导的严重结肠溃疡的实验模型中检测MSC的疗效。在该模型中，在照射后立即或三周（已建立病变）静脉注射骨髓间充质干细胞。MSC治疗可减少放射诱导的结肠溃疡，提高动物存活率。骨髓间充质干细胞不论输注时间长短，均可诱导治疗效果。在结肠中注入MSC移植物，但也增加了内源性MSC在血液中的动员，随着时间的推移具有持久的益处。体外分析表明，MSC效应是通过非典型WNT（无翼整合位点）途径通过旁分泌机制介导的。在受辐照的大鼠结肠中，MSC处理增加了上皮细胞非规范WNT4配体的表达。通过刺激SOX9（含基因9的SRY-box）祖细胞/干细胞标记物阳性的结肠上皮细胞，MSC注射后上皮细胞再生过程得到改善。本研究表明，MSC治疗诱导内源性宿主祖细胞的刺激，以改善再生过程，并构成了支持使用MSC来限制/减少辐射引起的结肠直肠损伤的初步方法。
Patients who undergo pelvic radiotherapy may develop severe and chronic complications resulting from gastrointestinal alterations. The lack of curative treatment highlights the importance of novel and effective therapeutic strategies. We thus tested the therapeutic benefit of mesenchymal stem cells (MSC) treatment and proposed molecular mechanisms of action. MSC efficacy was tested in an experimental model of radiation-induced severe colonic ulceration histologically similar to that observed in patients. In this model, MSC from bone marrow were administered intravenously, immediately or three weeks (established lesions) after irradiation. MSC therapy reduces radiation-induced colonic ulceration and increases animal survival. MSC treatment induces therapeutic efficacy whatever the time of cell infusion. Infused-MSC engraft in the colon but also increase endogenous MSC mobilization in blood that have lasting benefits over time. In vitro analysis demonstrates that the MSC effect is mediated by paracrine mechanisms through the non-canonical WNT (Wingless integration site) pathway. In irradiated rat colons, MSC treatment increases the expression of the non-canonical WNT4 ligand by epithelial cells. The epithelial regenerative process is improved after MSC injection by stimulation of colonic epithelial cells positive for SOX9 (SRY-box containing gene 9) progenitor/stem cell markers. This study demonstrates that MSC treatment induces stimulation of endogenous host progenitor cells to improve the regenerative process and constitutes an initial approach to arguing in favor of the use of MSC to limit/reduce colorectal damage induced by radiation.
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DOI：
10.1073/pnas.1013004108
发表时间：
2011-01-04
影响因子：
11.1
作者：
Montgomery, Robert K.;Carlone, Diana L.;Breault, David T.
通讯作者：
Breault, David T.
影响因子：
12.4
作者：
Leroux, Lionel;Descamps, Betty;Duplaa, Cecile
通讯作者：
Duplaa, Cecile
影响因子：
29.4
作者：
Gregorieff, A;Pinto, D;Clevers, H
通讯作者：
Clevers, H
影响因子：
2
作者：
Basinski, C;Fuller, E;Benson, JT
通讯作者：
Benson, JT
影响因子：
0.9
作者：
Mansilla, E.;Marin, G. H.;Soratti, C.
通讯作者：
Soratti, C.