Non-invasive imaging reveals conditions that impact distribution and persistence of cells after in vivo administration.
Non-invasive imaging reveals conditions that impact distribution and persistence of cells after in vivo administration.
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DOI：
10.1186/s13287-018-1076-x
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发表时间：
2018-11-28
影响因子：
7.5
通讯作者：
Wilm B
中科院分区：
文献类型：
--
作者：
Scarfe L;Taylor A;Sharkey J;Harwood R;Barrow M;Comenge J;Beeken L;Astley C;Santeramo I;Hutchinson C;Ressel L;Smythe J;Austin E;Levy R;Rosseinsky MJ;Adams DJ;Poptani H;Park BK;Murray P;Wilm B
基于细胞的再生医学疗法现在经常在临床试验中进行测试。在许多情况下，细胞治疗是全身性的，但对它们的命运知之甚少，而且不良事件往往被低估。目前，只能在临床前研究中评估细胞疗法的安全性和结局，特别是通过使用多模式成像方法纵向监测动物。在这里，使用一套体内成像模式来探索一系列人类和小鼠细胞的命运，我们研究了给药途径、细胞类型和宿主免疫状态如何影响给药细胞的命运。我们应用了一个独特的成像平台，结合生物发光，光声和磁共振成像模式，以评估不同的人类和小鼠细胞类型的安全性，通过以下它们的生物分布和持久性，在小鼠静脉或动脉系统给药后。纵向成像分析（i）表明，对于某些细胞类型，动脉内途径可能比静脉内给药更危险，（ii）揭示了小鼠间充质干细胞/基质细胞（MSC）系形成肿瘤的潜力取决于给药途径和小鼠品系，以及（iii）表明临床测试的人脐带（hUC）-当静脉内给药于小鼠时，衍生的MSC可以瞬时和出乎意料地增殖。为了对潜在的基于细胞的疗法进行充分的安全性评估，需要彻底了解给药后的细胞生物分布和命运。这里使用的非侵入性成像平台不仅可以显示这些治疗的一般器官分布，还可以详细了解它们在不同器官中的存在，重要的是，肿瘤发生的可能性。我们观察到hUC-MSC而不是人骨髓（hBM）衍生的MSC在一些动物中持续一段时间，这表明用这些细胞进行治疗应谨慎进行。本文的在线版本（10.1186/s13287-018-1076-x）包含补充材料，可供授权用户使用。
Cell-based regenerative medicine therapies are now frequently tested in clinical trials. In many conditions, cell therapies are administered systemically, but there is little understanding of their fate, and adverse events are often under-reported. Currently, it is only possible to assess safety and fate of cell therapies in preclinical studies, specifically by monitoring animals longitudinally using multi-modal imaging approaches. Here, using a suite of in vivo imaging modalities to explore the fate of a range of human and murine cells, we investigate how route of administration, cell type and host immune status affect the fate of administered cells. We applied a unique imaging platform combining bioluminescence, optoacoustic and magnetic resonance imaging modalities to assess the safety of different human and murine cell types by following their biodistribution and persistence in mice following administration into the venous or arterial system. Longitudinal imaging analyses (i) suggested that the intra-arterial route may be more hazardous than intravenous administration for certain cell types, (ii) revealed that the potential of a mouse mesenchymal stem/stromal cell (MSC) line to form tumours depended on administration route and mouse strain and (iii) indicated that clinically tested human umbilical cord (hUC)-derived MSCs can transiently and unexpectedly proliferate when administered intravenously to mice. In order to perform an adequate safety assessment of potential cell-based therapies, a thorough understanding of cell biodistribution and fate post administration is required. The non-invasive imaging platform used here can expose not only the general organ distribution of these therapies, but also a detailed view of their presence within different organs and, importantly, tumourigenic potential. Our observation that the hUC-MSCs but not the human bone marrow (hBM)-derived MSCs persisted for a period in some animals suggests that therapies with these cells should proceed with caution. The online version of this article (10.1186/s13287-018-1076-x) contains supplementary material, which is available to authorized users.
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影响因子：
4.3
作者：
Bárcia RN;Santos JM;Filipe M;Teixeira M;Martins JP;Almeida J;Água-Doce A;Almeida SC;Varela A;Pohl S;Dittmar KE;Calado S;Simões SI;Gaspar MM;Cruz ME;Lindenmaier W;Graça L;Cruz H;Cruz PE
通讯作者：
Cruz PE
影响因子：
5.2
作者：
Angelotti, Maria Lucia;Ronconi, Elisa;Romagnani, Paola
通讯作者：
Romagnani, Paola
影响因子：
4.4
作者：
Ittrich, Harald;Lange, Claudia;Nolte-Ernsting, Claus
通讯作者：
Nolte-Ernsting, Claus
DOI：
10.2106/00004623-199301000-00012
发表时间：
1993-01-01
影响因子：
5.3
作者：
DIDUCH, DR;COE, MR;BALIAN, G
通讯作者：
BALIAN, G
静脉注射HMSC改善了小鼠的心肌梗塞，因为栓塞在肺中的细胞被激活以分泌抗炎蛋白TSG-6。
影响因子：
23.9
作者：
Lee RH;Pulin AA;Seo MJ;Kota DJ;Ylostalo J;Larson BL;Semprun-Prieto L;Delafontaine P;Prockop DJ
通讯作者：
Prockop DJ