Synergism of hematopoietic cytokines for infarct repair.
Synergism of hematopoietic cytokines for infarct repair.
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造血细胞因子对梗死修复的协同作用。
DOI：
10.1161/01.res.0000222024.14452.7b
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发表时间：
2006
影响因子：
20.1
通讯作者：
Yoon,Young-sup
中科院分区：
文献类型：
--
作者：
Cho,Hyun-Jai;Yoon,Young-sup
在过去的几年里，干细胞生物学及其在心血管疾病中的治疗应用领域已经显着扩大，并移动到心血管科学的前沿。来自骨髓（BM）衍生的干细胞或祖细胞的实验研究的有希望的结果1 -3促使缺血性心脏病（IHD）的临床试验的开始。初步临床试验4，5表明，使用各种BM衍生细胞的细胞疗法对于治疗IHD是安全有效的。BM包括各种干细胞的发现产生了直接动员和归巢BM细胞进入心脏以再生受损组织的策略。6这个概念很吸引人，因为可以避免与获取和将BM细胞输送到心脏相关的侵入性程序。从BM动员干细胞的策略最初是由血液学家设计的，以加速癌症化疗后的恢复。7许多造血细胞因子，包括粒细胞集落刺激因子（G-CSF）、粒细胞巨噬细胞集落刺激因子（GM-CSF）、干细胞因子（SCF）、flt 3配体（FL）和促红细胞生成素，已经被测试用于造血系统的动员和再增殖。G-CSF是动物和患者中研究最广泛的造血生长因子。除了动员BM细胞外，G-CSF还诱导造血细胞的增殖、分化和存活。最近，据报道G-CSF对表达G-CSF受体的非造血细胞如心肌细胞、8内皮细胞、8和神经元细胞具有直接作用。克隆SCF作为c-kit的配体。9 SCF在骨髓造血的早期阶段发挥其活性，并与CSF协同作用。Flt 3是主要在HSC和祖细胞上表达的受体，并且与c-kit具有许多重叠活性。FL属于造血细胞因子家族，包括SCF和巨噬细胞集落刺激因子（M-CSF），对III类酪氨酸激酶受体具有特异性。10 FL在早期造血前体细胞的增殖、存活和分化中起核心作用。FL作为单一细胞因子通常不是有效的，但与G-CSF一起，它对HSC的动员和植入发挥协同作用。11
Over the past few years, the field of stem cell biology and its therapeutic application in cardiovascular diseases has expanded remarkably and moved to the forefront of cardiovascular science. Promising results from experimental studies with bone marrow (BM)-derived stem or progenitor cells1–3 prompted initiation of clinical trials in ischemic heart diseases (IHD). Pilot clinical trials4, 5 demonstrated that cell therapy using various BM-derived cells are safe and effective for treating IHD. The discovery that BM includes various stem cells spawned the strategy of directly mobilizing and homing BM cells into the heart to regenerate injured tissue. 6 This concept is appealing because invasive procedures related to harvesting and delivering BM cells into the heart can be avoided.The strategy of mobilizing stem cells from BM was initially contrived by hematologists to accelerate recovery after cancer chemotherapy. 7 A number of hematopoietic cytokines, including granulocyte colony-stimulating factor (G-CSF), granulocyte macrophage colony stimulating factor (GM-CSF), stem cell factor (SCF), flt3 ligand (FL), and erythropoietin have been tested for mobilization and repopulation of the hematopoietic system. G-CSF is the most widely investigated hematopoietic growth factor in animals and patients. In addition to mobilizing BM cells, G-CSF induces proliferation, differentiation, and survival of hematopoietic cells. Recently, G-CSF was reported to have a direct action on nonhematopoietic cells expressing G-CSF receptors such as cardiomyocytes, 8 endothelial cells, 8 and neuronal cells. SCF was cloned as a ligand for c-kit. 9 SCF exerts its activity at the early stages of hematopoiesis in BM and acts synergistically with CSFs. Flt3 is a receptor expressed predominantly on HSCs and progenitors and has many overlapping activities with c-kit. FL belongs to a family of hematopoietic cytokines, including SCF and macrophage colony-stimulating factor (M-CSF), that are specific for class III tyrosine kinase receptors. 10 FL plays a central role in the proliferation, survival, and differentiation of early hematopoietic precursor cells. FL is usually not efficient as a single cytokine, but with G-CSF it exerts synergistic effects on mobilization and engraftment of HSCs. 11