Biomaterials Unit, International Center for Materials Nanoarchitectonics (MANA), National Institute for Materials Science (NIMS), Tsukuba, Japan.
Curr Med Chem. 2013;20(28):3429-47. doi: 10.2174/09298673113209990032.
The contribution of adult stem cells to cardiac repair is mostly ascribed to an indirect paracrine effect, rather than to their actual engraftment and differentiation into new contractile and vascular cells. This effect consists in a direct reduction of host cell death, promotion of neovascularization, and in a "bystander effect" on local inflammation. A number of cytokines secreted by adult stem/progenitor cells has been proposed to be responsible for the consistent beneficial effect reported in the early attempts to deliver different stem cell subsets to the injured myocardium. Aiming to maximize their beneficial activity on the diseased myocardium, the genetic modification of adult stem cells to enhance and/or control the secretion of specific cytokines would turn them into active drug delivery vectors. On the other hand, engineering biocompatible scaffolds as to release paracrine factors could result in multiple advantages: (1) achieve a local controlled release of the drug of interest, thus minimizing off-target effects, (2) enhance stem cell retention in the injured area and (3) boost the beneficial paracrine effects exerted by adult stem cells on the host tissue. In the present review, a critical overview of the state-of-the-art in the modification of stem cells and the functionalization of biocompatible scaffolds to deliver beneficial soluble factors to the injured myocardium is offered. Besides the number of concerns to be addressed before a clinical application can be foreseen for such concepts, this path could translate into the generation of active scaffolds as smart cell and drug delivery systems for cardiac repair.
成体干细胞对心脏修复的贡献主要归因于间接旁分泌作用，而不是其实际的植入和分化为新的收缩和血管细胞。这种作用包括直接减少宿主细胞死亡、促进新血管生成，以及对局部炎症的“旁观者效应”。许多由成体干细胞/祖细胞分泌的细胞因子被认为是导致早期尝试将不同的干细胞亚群递送到受损心肌时报告的一致有益效果的原因。为了最大限度地提高其对患病心肌的有益活性，可以对成体干细胞进行基因修饰，以增强和/或控制特定细胞因子的分泌，从而将其转化为活性药物输送载体。另一方面，设计生物相容性支架以释放旁分泌因子可能会带来多种优势：（1）实现感兴趣药物的局部控制释放，从而最小化脱靶效应；（2）增强干细胞在受损区域的保留；（3）增强成体干细胞对宿主组织发挥的有益旁分泌作用。在本综述中，对修饰干细胞和功能化生物相容性支架以将有益的可溶性因子递送到受损心肌的最新技术进行了批判性概述。除了在可以预见此类概念的临床应用之前需要解决的许多问题外，这一途径还可以转化为活性支架的生成，作为心脏修复的智能细胞和药物输送系统。
