Stem Cell Institute, James Graham Brown Cancer Center, University of Louisville, Louisville, KY, USA.
Department of Molecular Genetics, Institute of Bioorganic Chemistry, Polish Academy of Sciences, Poznan, Poland.
Methods Mol Biol. 2023;2567:263-280. doi: 10.1007/978-1-0716-2679-5_17.
Mobilization or egress of stem cells from bone marrow (BM) into peripheral blood (PB) is an evolutionary preserved and important mechanism in an organism for self-defense and regeneration. BM-derived stem cells circulate always at steady-state conditions in PB, and their number increases during stress situations related to (a) infections, (b) tissue organ injury, (c) stress, and (d) strenuous exercise. Stem cells also show a circadian pattern of their PB circulating level with peak in early morning hours and nadir late at night. The number of circulating in PB stem cells could be pharmacologically increased after administration of some drugs such as cytokine granulocyte colony-stimulating factor (G-CSF) or small molecular antagonist of CXCR4 receptor AMD3100 (Plerixafor) that promote their egress from BM into PB and lymphatic vessels. Circulating can be isolated from PB for transplantation purposes by leukapheresis. This important homeostatic mechanism is governed by several intrinsic complementary pathways. In this chapter, we will discuss the role of purinergic signaling and extracellular nucleotides in regulating this process and review experimental strategies to study their involvement in mobilization of various types of stem cells that reside in murine BM.
骨髓(BM)中的干细胞向外周血(PB)的动员或迁出是生物体自我防御和再生的一种进化上保守且重要的机制。在 PB 中,BM 来源的干细胞始终处于稳定状态循环,并且在与(a)感染、(b)组织器官损伤、(c)应激和(d)剧烈运动相关的应激情况下其数量会增加。干细胞的 PB 循环水平也存在昼夜节律模式,峰值出现在清晨,低谷出现在深夜。一些药物(如细胞因子粒细胞集落刺激因子(G-CSF)或 CXCR4 受体小分子拮抗剂 AMD3100(plerixafor))给药后,干细胞向 PB 和淋巴管的迁出会增加 PB 中循环的干细胞数量,从而增加其数量。可以通过白细胞分离术从 PB 中分离出用于移植的循环细胞。这种重要的体内平衡机制受几个内在互补途径的控制。在本章中,我们将讨论嘌呤能信号转导和细胞外核苷酸在调节这一过程中的作用,并综述研究其在各种驻留在鼠 BM 中的干细胞动员中的作用的实验策略。