Identification of cardiac stem cells within mature cardiac myocytes

Cardiac stem cells are described in a number of mammalian species including humans. Cardiac stem cell clusters consisting of both lineage-negative and partially committed cells are generally identified between contracting cardiac myocytes. In the present study, c-kit⁺, Sca⁺, and Isl1⁺ stem cells were revealed to be located <i>inside</i> the sarcoplasm of cardiac myocytes in myocardial cell cultures derived from newborn, 20-, and 40-day-old rats. Intracellularly localized cardiac stem cells had a coating or capsule with a few pores that opened into the host cell sarcoplasm. The similar structures were also identified in the suspension of freshly isolated myocardial cells (ex vivo) of 20- and 40-day-old rats. The results from this study provide direct evidence for the replicative division of encapsulated stem cells, followed by their partial cardiomyogenic differentiation. The latter is substantiated by the release of multiple transient amplifying cells following the capsule rupture. In conclusion, functional cardiac stem cells can reside not only exterior to but also within cardiomyocytes.

目前已在包括人类在内的多种哺乳动物物种中报道过心脏干细胞（cardiac stem cells）。由谱系阴性（lineage-negative）细胞与部分定型细胞共同构成的心脏干细胞簇，通常定位于收缩性心肌细胞之间。本研究发现，在新生、20日龄及40日龄大鼠的心肌细胞培养物中，c-kit⁺、Sca⁺与Isl1⁺干细胞定位于心肌细胞的肌浆内部。这类胞内定位的心脏干细胞带有一层包膜或囊壳，存在若干开孔并与宿主细胞的肌浆相通。在20日龄和40日龄大鼠新鲜分离的心肌细胞离体（ex vivo）悬液中，也观察到了类似结构。本研究结果为带囊壳干细胞的复制分裂及其后续的部分心肌向分化提供了直接证据。这一过程可通过囊壳破裂后释放的多种瞬时扩增细胞得到证实。综上，具有功能的心脏干细胞不仅可存在于心肌细胞外侧，也可定位于心肌细胞内部。