Designing 3D Mesenchymal Stem Cell Sheets Merging Magnetic and Fluorescent Features: When Cell Sheet Technology Meets Image-Guided Cell Therapy.
Designing 3D Mesenchymal Stem Cell Sheets Merging Magnetic and Fluorescent Features: When Cell Sheet Technology Meets Image-Guided Cell Therapy.
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DOI：
10.7150/thno.14064
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发表时间：
2016
期刊：
影响因子：
12.4
通讯作者：
Clément O
中科院分区：
文献类型：
--
作者：
Rahmi G;Pidial L;Silva AK;Blondiaux E;Meresse B;Gazeau F;Autret G;Balvay D;Cuenod CA;Perretta S;Tavitian B;Wilhelm C;Cellier C;Clément O
细胞片技术通过提供易于植入的无支架3D组织构建体，为组织再生治疗开辟了新的前景。许多研究都集中在细胞片植入的治疗效果，而相对较少关注植入细胞在体内的命运。本研究的目的是纵向跟踪植入在靶组织中的细胞片层中的细胞。为此，我们（i）赋予骨髓间充质干细胞（BMMSC）的成像特性，通过荧光和磁性示踪剂的双重标记，（ii）应用BMMSC细胞片在小鼠消化道瘘模型，（iii）跟踪BMMSC的命运在体内的MRI和探针为基础的共聚焦激光显微内镜（pCLE），和（iv）量化瘘的愈合。我们发现，图像引导的纵向随访可以记录细胞片衍生的BMMSCs的命运及其愈合能力。此外，我们的治疗诊断方法告知作用机制，直接通过将细胞片衍生的BMMSC整合到宿主组织中或间接通过在宿主组织中释放信号分子。多模式成像和临床评价共同证明细胞片移植导致最小的临床炎症，改善瘘愈合，减少组织纤维化和增强微血管密度。在分子水平上，细胞片移植诱导抗炎细胞因子（TGF-β 2和IL-10）和参与组织修复的宿主肠生长因子（EGF和VEGF）的表达增加。多模态成像对于跟踪细胞片层和对其再生特性的非侵入性随访是有用的。
Cell sheet technology opens new perspectives in tissue regeneration therapy by providing readily implantable, scaffold-free 3D tissue constructs. Many studies have focused on the therapeutic effects of cell sheet implantation while relatively little attention has concerned the fate of the implanted cells in vivo. The aim of the present study was to track longitudinally the cells implanted in the cell sheets in vivo in target tissues. To this end we (i) endowed bone marrow-derived mesenchymal stem cells (BMMSCs) with imaging properties by double labeling with fluorescent and magnetic tracers, (ii) applied BMMSC cell sheets to a digestive fistula model in mice, (iii) tracked the BMMSC fate in vivo by MRI and probe-based confocal laser endomicroscopy (pCLE), and (iv) quantified healing of the fistula. We show that image-guided longitudinal follow-up can document both the fate of the cell sheet-derived BMMSCs and their healing capacity. Moreover, our theranostic approach informs on the mechanism of action, either directly by integration of cell sheet-derived BMMSCs into the host tissue or indirectly through the release of signaling molecules in the host tissue. Multimodal imaging and clinical evaluation converged to attest that cell sheet grafting resulted in minimal clinical inflammation, improved fistula healing, reduced tissue fibrosis and enhanced microvasculature density. At the molecular level, cell sheet transplantation induced an increase in the expression of anti-inflammatory cytokines (TGF-ß2 and IL-10) and host intestinal growth factors involved in tissue repair (EGF and VEGF). Multimodal imaging is useful for tracking cell sheets and for noninvasive follow-up of their regenerative properties.