Speidel Alessondra T, Stuckey Daniel J, Chow Lesley W, Jackson Laurence H, Noseda Michela, Abreu Paiva Marta, Schneider Michael D, Stevens Molly M
British Heart Foundation Centre of Research Excellence, Department of Materials, Department of Bioengineering, Institute for Biomedical Engineering, and National Heart and Lung Institute, Imperial College London, London, SW7 2AZ, United Kingdom.
Centre for Advanced Biomedical Imaging (CABI), University College London, London WC1E 6DD, United Kingdom.
ACS Cent Sci. 2017 Apr 26;3(4):338-348. doi: 10.1021/acscentsci.7b00039. Epub 2017 Mar 30.
Retention and survival of transplanted cells are major limitations to the efficacy of regenerative medicine, with short-term paracrine signals being the principal mechanism underlying current cell therapies for heart repair. Consequently, even improvements in short-term durability may have a potential impact on cardiac cell grafting. We have developed a multimodal hydrogel-based platform comprised of a poly(ethylene glycol) network cross-linked with bioactive peptides functionalized with Gd(III) in order to monitor the localization and retention of the hydrogel in vivo by magnetic resonance imaging. In this study, we have tailored the material for cardiac applications through the inclusion of a heparin-binding peptide (HBP) sequence in the cross-linker design and formulated the gel to display mechanical properties resembling those of cardiac tissue. Luciferase-expressing cardiac stem cells (CSC-Luc2) encapsulated within these gels maintained their metabolic activity for up to 14 days in vitro. Encapsulation in the HBP hydrogels improved CSC-Luc2 retention in the mouse myocardium and hind limbs at 3 days by 6.5- and 12- fold, respectively. Thus, this novel heparin-binding based, Gd(III)-tagged hydrogel and CSC-Luc2 platform system demonstrates a tailored, in vivo detectable theranostic cell delivery system that can be implemented to monitor and assess the transplanted material and cell retention.
移植细胞的留存和存活是再生医学疗效的主要限制因素，短期旁分泌信号是当前心脏修复细胞疗法的主要作用机制。因此，即使是短期耐久性的改善也可能对心脏细胞移植产生潜在影响。我们开发了一种基于多模态水凝胶的平台，该平台由聚乙二醇网络与用钆（III）功能化的生物活性肽交联而成，以便通过磁共振成像监测水凝胶在体内的定位和留存情况。在本研究中，我们通过在交联剂设计中加入肝素结合肽（HBP）序列，对用于心脏应用的材料进行了定制，并配制了凝胶使其具有类似于心脏组织的机械性能。封装在这些凝胶中的表达荧光素酶的心脏干细胞（CSC-Luc2）在体外长达14天内保持其代谢活性。在HBP水凝胶中封装可使CSC-Luc2在3天时在小鼠心肌和后肢中的留存率分别提高6.5倍和12倍。因此，这种新型的基于肝素结合、钆（III）标记的水凝胶和CSC-Luc2平台系统展示了一种可定制的、体内可检测的治疗诊断细胞递送系统，可用于监测和评估移植材料及细胞留存情况。
