Department of Physiology, Pusan National University School of Medicine, Yangsan, 50612, Republic of Korea.
Research Institute of Convergence Biomedical Science and Technology, Pusan National University Yangsan Hospital, Yangsan, Gyeongsangnam-do, 50612, Republic of Korea.
Arch Pharm Res. 2019 Mar;42(3):224-231. doi: 10.1007/s12272-019-01123-2. Epub 2019 Jan 24.
Stem cell mobilization plays important roles in the treatment of severe ischemic diseases, including myocardial infarction, limb ischemia, ischemic stroke, and acute kidney injury. Stem cell mobilization refers to the egress of heterogeneous stem cells residing in the bone marrow into the peripheral blood. In the clinic, granulocyte colony-stimulating factor (G-CSF) is the drug most commonly used to induce stem cell mobilization. Plerixafor, a direct antagonist of CXCR4, is also frequently used alone or in combination with G-CSF to mobilize stem cells. The molecular mechanisms by which G-CSF induces stem cell mobilization are well characterized. Briefly, G-CSF activates neutrophils in the bone marrow, which then release proteolytic enzymes, such as neutrophil elastase, cathepsin G, and matrix metalloproteinase 9, which cleave a variety of molecules responsible for stem cell retention in the bone marrow, including CXCL12, VCAM-1, and SCF. Subsequently, stem cells are released from the bone marrow into the peripheral blood. The released stem cells can be collected and used in autologous or allogeneic transplantation. To identify better conditions for stem cell mobilization in the treatment of acute and chronic ischemic diseases, several preclinical and clinical studies have been conducted over the past decade on various mobilizing agents. In this paper, we are going to review methods that induce mobilization of stem cells from the bone marrow and introduce the application of stem cell mobilization to therapy of ischemic diseases.
干细胞动员在治疗严重缺血性疾病中起着重要作用，包括心肌梗死、肢体缺血、缺血性中风和急性肾损伤。干细胞动员是指骨髓中异质性干细胞进入外周血的过程。临床上，粒细胞集落刺激因子（G-CSF）是最常用于诱导干细胞动员的药物。CXCR4 的直接拮抗剂plerixafor 也常单独或与 G-CSF 联合用于动员干细胞。G-CSF 诱导干细胞动员的分子机制已得到很好的描述。简而言之，G-CSF 激活骨髓中的中性粒细胞，然后释放蛋白酶，如中性粒细胞弹性蛋白酶、组织蛋白酶 G 和基质金属蛋白酶 9，它们切割各种负责干细胞在骨髓中保留的分子，包括 CXCL12、VCAM-1 和 SCF。随后，干细胞从骨髓释放到外周血中。释放的干细胞可以被收集并用于自体或同种异体移植。为了在治疗急性和慢性缺血性疾病中找到更好的干细胞动员条件，过去十年中进行了几项关于各种动员剂的临床前和临床试验。在本文中，我们将回顾从骨髓中动员干细胞的方法，并介绍干细胞动员在治疗缺血性疾病中的应用。
