Decuzzi Paolo
Houston Methodist Hospital Research Institute, Houston Methodist Hospital, Houston, Texas.
Methodist Debakey Cardiovasc J. 2013 Oct-Dec;9(4):223-8. doi: 10.14797/mdcj-9-4-223.
Stem cell transplantation has the potential to restore heart function following myocardial infarction. However, the success of any stem cell-based therapy is critically linked to the effective homing and early engraftment of the injected cells at the infarcted site. Here, a hierarchical multiscale computational model is proposed for predicting the patient-specific vascular transport and intratissue homing and migration of stem cells injected either systemically or locally. Starting with patient-specific data, such as the vascular geometry, blood flow, and location of the infarcted area, the computational model can be used to perform parametric analysis to identify optimal injection conditions in terms of administration route, injection site, catheter type, and infusion velocity. In addition to this, a new generation of magnetic nanoconstructs is introduced for labeling stem cells and monitoring their behavior in vivo via magnetic resonance imaging. These nanoconstructs also can be used for multimodal imaging, merging MRI and nuclear imaging, and the intracellular delivery of active agents to support stem cell differentiation. The convergence of computational modeling and novel nanoconstructs for stem cell labeling could improve our understanding in cell homing and early engraftment at the infarcted site and thus pave the way to more effective stem cell-based therapies.
干细胞移植具有在心肌梗死后恢复心脏功能的潜力。然而,任何基于干细胞的治疗的成功都与注入细胞在梗死部位的有效归巢和早期植入密切相关。在此,提出了一种分层多尺度计算模型,用于预测全身或局部注射的干细胞在患者特定的血管运输以及组织内的归巢和迁移情况。从患者特定的数据(如血管几何形状、血流和梗死区域位置)出发,该计算模型可用于进行参数分析,以确定在给药途径、注射部位、导管类型和输注速度方面的最佳注射条件。除此之外,还引入了新一代磁性纳米构建体用于标记干细胞,并通过磁共振成像在体内监测它们的行为。这些纳米构建体还可用于多模态成像,将磁共振成像和核成像相结合,以及将活性剂进行细胞内递送以支持干细胞分化。用于干细胞标记的计算建模与新型纳米构建体的融合,可能会增进我们对梗死部位细胞归巢和早期植入的理解,从而为更有效的基于干细胞的治疗铺平道路。