Hoshino K, Kimura T, De Grand A M, Yoneyama R, Kawase Y, Houser S, Ly H Q, Kushibiki T, Furukawa Y, Ono K, Tabata Y, Frangioni J V, Kita T, Hajjar R J, Hayase M
Cardiology Laboratory for Integrative Physiology and Imaging, Massachusetts General Hospital, Harvard Medical School, Boston, MA 02114, USA.
Gene Ther. 2006 Sep;13(18):1320-7. doi: 10.1038/sj.gt.3302793. Epub 2006 May 18.
Gelatin hydrogel microspheres (GHMs) have been reported as novel non-viral vectors for gene or protein delivery (GHM therapy). However, the components of an effective catheter-based delivery strategy for GHM therapy are unknown. We evaluated the effectiveness of three catheter-based strategies for cardiac GHM therapy: (1) antegrade injection (AI) via coronary arteries; (2) retrograde injection (RI) via coronary veins; and (3) direct myocardial injection (DI) via the coronary sinus. AI distributed microspheres homogeneously throughout the target area with 73+/-11% retention. RI scattered microspheres non-homogenously with 22+/-8% retention. DI distributed microspheres in the needle-advanced area with 47+/-14% retention. However, despite high efficiency, AI did not show biological effects of inducing angiogenesis from basic fibroblast growth factor bound to GHMs. Furthermore, focal micro-infarctions, owing to micro-embolism of aggregated GHMs into small coronary arterioles, were detected in the AI group. Conversely, only RI and DI groups displayed increased coronary flow reserve. DI groups also demonstrated increased capillary density. These results suggest that RI and DI are effective for cardiac GHM therapy, while AI appears inappropriate owing to the risk of focal infarctions.
明胶水凝胶微球（GHMs）已被报道为用于基因或蛋白质递送的新型非病毒载体（GHM疗法）。然而，基于导管的有效GHM治疗策略的组成部分尚不清楚。我们评估了三种基于导管的心脏GHM治疗策略的有效性：（1）经冠状动脉顺行注射（AI）；（2）经冠状静脉逆行注射（RI）；以及（3）经冠状窦直接心肌注射（DI）。AI使微球均匀分布于整个靶区域，滞留率为73±11%。RI使微球分布不均匀，滞留率为22±8%。DI使微球分布于进针区域，滞留率为47±14%。然而，尽管效率高，但AI未显示出与结合在GHMs上的碱性成纤维细胞生长因子诱导血管生成的生物学效应。此外，在AI组中检测到由于聚集的GHMs微栓塞进入小冠状动脉而导致的局灶性微梗死。相反，只有RI组和DI组显示冠状动脉血流储备增加。DI组还显示毛细血管密度增加。这些结果表明，RI和DI对心脏GHM治疗有效，而AI由于存在局灶性梗死的风险似乎不合适。
