Department of Chemical Engineering and Institute of Biomedical Engineering, National Tsing Hua University, Hsinchu, 30013, Taiwan (ROC).
Adv Healthc Mater. 2014 Aug;3(8):1133-48. doi: 10.1002/adhm.201300605. Epub 2014 Jan 27.
Cell transplantation via direct intramuscular injection is a promising therapy for patients with ischemic diseases. However, following injections, retention of transplanted cells in engrafted areas remains problematic, and can be deleterious to cell-transplantation therapy. In this Progress Report, a thermoresponsive hydrogel system composed of aqueous methylcellulose (MC) blended with phosphate-buffered saline is constructed to grow cell sheet fragments and cell bodies for the treatment of ischemic diseases. The as-prepared MC hydrogel system undergoes a sol-gel reversible transition upon heating or cooling at ≈32 °C. Via this unique property, the grown cell sheet fragments (cell bodies) can be harvested without using proteolytic enzymes; consequently, their inherent extracellular matrices (ECMs) and integrative adhesive agents remain well preserved. In animal studies using rats and pigs with experimentally created myocardial infarction, the injected cell sheet fragments (cell bodies) become entrapped in the interstices of muscular tissues and adhere to engraftment sites, while a minimal number of cells exist in the group receiving dissociated cells. Moreover, transplantation of cell sheet fragments (cell bodies) significantly increases vascular density, thereby improving the function of an infarcted heart. These experimental results demonstrate that cell sheet fragments (cell bodies) function as a cell-delivery construct by providing a favorable ECM environment to retain transplanted cells locally and consequently, improving the efficacy of therapeutic cell transplantation.
通过直接肌内注射进行细胞移植是治疗缺血性疾病患者的一种很有前途的疗法。然而，在注射后，移植细胞在植入部位的保留仍然是一个问题，并且可能对细胞移植治疗有害。在本进展报告中，构建了一种由水性甲基纤维素（MC）与磷酸盐缓冲盐水混合而成的温敏水凝胶系统，用于生长细胞片片段和细胞体，以治疗缺血性疾病。所制备的 MC 水凝胶系统在约 32°C 加热或冷却时经历溶胶-凝胶可逆转变。通过这种独特的特性，可以在不使用蛋白水解酶的情况下收获生长的细胞片片段（细胞体）；因此，它们固有的细胞外基质（ECM）和整合的粘附剂得以很好地保留。在使用大鼠和猪进行的实验性心肌梗死动物研究中，注射的细胞片片段（细胞体）被捕获在肌肉组织的间隙中并附着在植入部位，而在接受分离细胞的组中只有少数细胞存在。此外，移植细胞片片段（细胞体）显著增加了血管密度，从而改善了梗死心脏的功能。这些实验结果表明，细胞片片段（细胞体）作为一种细胞输送构建体发挥作用，为局部保留移植细胞提供了有利的 ECM 环境，从而提高了治疗性细胞移植的疗效。
