Department of Integrative Medical Sciences, Northeast Ohio Medical University, Rootstown, OH 44272, USA.
Department of Anatomy and Neuroscience, Northeast Ohio Medical University, Rootstown, OH 44272, USA.
Cells. 2023 Jan 6;12(2):242. doi: 10.3390/cells12020242.
Many clinical trials have attempted to use stem cells to treat ischemic heart diseases (IHD), but the benefits have been modest. Though coronary collaterals can be a "natural bypass" for IHD patients, the regulation of coronary collateral growth (CCG) and the role of endogenous stem cells in CCG are not fully understood. In this study, we used a bone marrow transplantation scheme to study the role of bone marrow stem cells (BMSCs) in a rat model of CCG. Transgenic GFP rats were used to trace BMSCs after transplantation; GFP bone marrow was harvested or sorted for bone marrow transplantation. After recovering from transplantation, the recipient rats underwent 10 days of repetitive ischemia (RI), with echocardiography before and after RI, to measure cardiac function and myocardial blood flow. At the end of RI, the rats were sacrificed for the collection of bone marrow for flow cytometry or heart tissue for imaging analysis. Our study shows that upon RI stimulation, BMSCs homed to the recipient rat hearts' collateral-dependent zone (CZ), proliferated, differentiated into endothelial cells, and engrafted in the vascular wall for collateral growth. These RI-induced collaterals improved coronary blood flow and cardiac function in the recipients' hearts during ischemia. Depletion of donor CD34 BMSCs led to impaired CCG in the recipient rats, indicating that this cell population is essential to the process. Overall, these results show that BMSCs contribute to CCG and suggest that regulation of the function of BMSCs to promote CCG might be a potential therapeutic approach for IHD.
许多临床试验都试图利用干细胞来治疗缺血性心脏病（IHD），但收效甚微。虽然冠状侧支循环可以作为 IHD 患者的“天然旁路”，但冠状侧支循环生长（CCG）的调节和内源性干细胞在 CCG 中的作用尚未完全了解。在这项研究中，我们使用骨髓移植方案来研究骨髓干细胞（BMSCs）在大鼠 CCG 模型中的作用。使用转绿色荧光蛋白（GFP）大鼠来追踪移植后的 BMSCs；采集 GFP 骨髓进行骨髓移植或分选。移植后恢复后，受体大鼠接受 10 天的重复缺血（RI），在 RI 前后进行超声心动图检查，以测量心脏功能和心肌血流。在 RI 结束时，处死大鼠以收集骨髓进行流式细胞术或心脏组织进行成像分析。我们的研究表明，在 RI 刺激下，BMSCs 归巢到受体大鼠心脏的侧支依赖区（CZ），增殖、分化为内皮细胞，并在血管壁中植入以促进侧支生长。这些由 RI 诱导的侧支在缺血期间改善了受体心脏的冠状动脉血流和心功能。耗尽供体 CD34 BMSCs 导致受体大鼠的 CCG 受损，表明该细胞群对这一过程至关重要。总体而言，这些结果表明 BMSCs 有助于 CCG，并提示调节 BMSCs 的功能以促进 CCG 可能是治疗 IHD 的一种潜在方法。
