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Role of stem cell mobilization in the treatment of ischemic diseases

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Abstract

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.

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Acknowledgements

This research was supported by the MRC program (NRF-2015R1A5A2009656) and the National Research Foundation of Korea (NRF) funded by the Ministry of Education, Science and Technology (NRF-2015M3A9C6030280; NRF-2017M3A9B4051542).

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  1. Department of Physiology, Pusan National University School of Medicine, Yangsan, 50612, Republic of Korea

    Seong Gyu Kwon, Insoo Park, Yang Woo Kwon, Tae Wook Lee, Gyu Tae Park & Jae Ho Kim

  2. Research Institute of Convergence Biomedical Science and Technology, Pusan National University Yangsan Hospital, Yangsan, Gyeongsangnam-do, 50612, Republic of Korea

    Jae Ho Kim

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  1. Seong Gyu Kwon
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Kwon, S.G., Park, I., Kwon, Y.W. et al. Role of stem cell mobilization in the treatment of ischemic diseases. Arch. Pharm. Res. 42, 224–231 (2019). https://doi.org/10.1007/s12272-019-01123-2

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