The dual effect of mesenchymal stem cells on tumour growth and tumour angiogenesis.
The dual effect of mesenchymal stem cells on tumour growth and tumour angiogenesis.
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DOI：
10.1186/scrt195
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发表时间：
2013-04-29
影响因子：
7.5
通讯作者：
Rome C
中科院分区：
文献类型：
--
作者：
Kéramidas M;de Fraipont F;Karageorgis A;Moisan A;Persoons V;Richard MJ;Coll JL;Rome C
了解人类间充质干细胞（hMSCs）所发挥的多种生物学功能以及它们作为再生医学或癌症治疗的治疗剂的发展是研究的主要领域。事实上，已经确定hMSC在肿瘤的发病机制和进展中发挥核心作用，但它们对肿瘤生长的影响仍然存在争议。在这项研究中，我们研究了hMSCs对预先建立的肿瘤生长的影响。我们将转移酶阳性的小鼠腺癌细胞（TSA-Luc+）移植到裸鼠体内，以获得皮下或肺肿瘤。当通过非侵入性生物发光成像确认肿瘤存在时，将hMSC注射到SC肿瘤的外周中或通过全身静脉注射递送到携带SC肿瘤或肺转移的小鼠中。无论hMSC注射的肿瘤模型和模式如何，hMSC给药总是与肿瘤生长降低相关，这是由于抑制肿瘤细胞增殖，可能是由于肿瘤血管生成的深度修饰。事实上，我们确定，尽管hMSC可以在小鼠的非肿瘤纤维素海绵模型中诱导新血管的形成，但它们不会改变递送到SC肿瘤或肺转移中的血红蛋白的总量。我们观察到这些肿瘤血管数量减少，但更长。我们的研究结果表明，hMSCs注射减少了小鼠体内实体瘤的生长，并改变了肿瘤血管系统，这证实了hMSCs可用于治疗预先建立的肿瘤。
Understanding the multiple biological functions played by human mesenchymal stem cells (hMSCs) as well as their development as therapeutics in regenerative medicine or in cancer treatment are major fields of research. Indeed, it has been established that hMSCs play a central role in the pathogenesis and progression of tumours, but their impact on tumour growth remains controversial. In this study, we investigated the influence of hMSCs on the growth of pre-established tumours. We engrafted nude mice with luciferase-positive mouse adenocarcinoma cells (TSA-Luc+) to obtain subcutaneous or lung tumours. When tumour presence was confirmed by non-invasive bioluminescence imaging, hMSCs were injected into the periphery of the SC tumours or delivered by systemic intravenous injection in mice bearing either SC tumours or lung metastasis. Regardless of the tumour model and mode of hMSC injection, hMSC administration was always associated with decreased tumour growth due to an inhibition of tumour cell proliferation, likely resulting from deep modifications of the tumour angiogenesis. Indeed, we established that although hMSCs can induce the formation of new blood vessels in a non-tumoural cellulose sponge model in mice, they do not modify the overall amount of haemoglobin delivered into the SC tumours or lung metastasis. We observed that these tumour vessels were reduced in number but were longer. Our results suggest that hMSCs injection decreased solid tumour growth in mice and modified tumour vasculature, which confirms hMSCs could be interesting to use for the treatment of pre-established tumours.
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影响因子：
3.1
作者：
Andrade, SP;Machado, RDP;Beraldo, WT
通讯作者：
Beraldo, WT
影响因子：
11.5
作者：
Hung, SC;Deng, WP;Gelovani, JG
通讯作者：
Gelovani, JG
影响因子：
33.6
作者：
Goel S;Duda DG;Xu L;Munn LL;Boucher Y;Fukumura D;Jain RK
通讯作者：
Jain RK
影响因子：
5.2
作者：
Klopp, Ann H.;Gupta, Anshul;Spaeth, Erika;Andreeff, Michael;Marini, Frank, III
通讯作者：
Marini, Frank, III
影响因子：
64.8
作者：
Karnoub, Antoine E.;Dash, Ajeeta B.;Weinberg, Robert A.
通讯作者：
Weinberg, Robert A.