Rosen Michael R, Brink Peter R, Cohen Ira S, Robinson Richard B
Department of Pharmacology, Center for Molecular Therapeutics, College of Physicians and Surgeons of Columbia University, New York, NY 10032, USA.
Med Biol Eng Comput. 2007 Feb;45(2):157-66. doi: 10.1007/s11517-006-0060-2. Epub 2006 May 31.
Biological pacemaking as a replacement for or adjunct to electronic pacemakers has been a subject of interest since the 1990s. In the following pages, we discuss the rational for and progress made using a hyperpolarization activated, cyclic nucleotide gated channel isoform to carry the I(f) pacemaker current in gene and cell therapy approaches. Both strategies have resulted in effective biological pacemaker function over a period of weeks in intact animals. Moreover, the use of adult human mesenchymal stem cells as a platform for carrying pacemaker genes has resulted in the formation of functional gap junctions with cardiac myocytes in situ leading to effective and persistent propagation of pacemaker current. The approaches described are encouraging, suggesting that biological pacemakers based on this strategy can be brought to clinical testing.
自20世纪90年代以来，生物起搏作为电子起搏器的替代或辅助手段一直是人们关注的课题。在接下来的几页中，我们将讨论在基因和细胞治疗方法中，使用超极化激活的环核苷酸门控通道亚型来携带I(f)起搏电流的原理和取得的进展。这两种策略都已在完整动物体内实现了数周的有效生物起搏功能。此外，将成人骨髓间充质干细胞用作携带起搏基因的平台，已导致在原位与心肌细胞形成功能性间隙连接，从而使起搏电流有效且持续地传播。所描述的这些方法令人鼓舞，表明基于该策略的生物起搏器可以进入临床试验阶段。
