Ratajczak Mariusz Z, Suszynska Malwina
Stem Cell Institute at the James Graham Brown Cancer Center, University of Louisville, 500 S. Floyd Street, Rm. 107, Louisville, KY, 40202, USA.
Department of Regenerative Medicine, Medical University of Warsaw, Warsaw, Poland.
Stem Cell Rev Rep. 2016 Feb;12(1):121-8. doi: 10.1007/s12015-015-9625-5.
Successful clinical outcomes from transplantation of hematopoietic stem cells (HSCs) depend upon efficient HSC homing to bone marrow (BM), subsequent engraftment, and, finally, BM repopulation. Homing of intravenously administered HSCs from peripheral blood (PB) through the circulation to the BM stem cell niches, which is the first critical step that precedes their engraftment, is enforced by chemotactic factors released in the BM microenvironment that chemoattract HSCs. These chemotactic factors include α-chemokine stromal-derived factor 1 (SDF-1), the bioactive phosphosphingolipids sphingosine-1-phosphate (S1P) and ceramid-1-phosphate (C1P), and the extracellular nucleotides ATP and UTP. Stem cells may also respond to a Ca(2+) or H(+) gradient by employing calcium- or proton-sensing receptors, respectively. In this review, we will present emerging strategies based on ex vivo manipulation of graft HSCs that are aimed at enhancing the responsiveness of HSCs to BM-secreted chemoattractants and/or promoting HSC adhesion and seeding efficiency in the BM microenvironment.
造血干细胞（HSC）移植的成功临床结果取决于HSC向骨髓（BM）的有效归巢、随后的植入，以及最终的BM再填充。静脉注射的HSC从外周血（PB）通过循环归巢到BM干细胞龛，这是它们植入之前的第一个关键步骤，由BM微环境中释放的趋化因子驱动，这些趋化因子对HSC具有化学趋化作用。这些趋化因子包括α-趋化因子基质衍生因子1（SDF-1）、生物活性磷酸鞘脂鞘氨醇-1-磷酸（S1P）和神经酰胺-1-磷酸（C1P），以及细胞外核苷酸ATP和UTP。干细胞也可能分别通过使用钙或质子感应受体对Ca(2+)或H(+)梯度作出反应。在这篇综述中，我们将介绍基于对移植物HSC进行体外操作的新兴策略，这些策略旨在增强HSC对BM分泌的趋化因子的反应性和/或提高HSC在BM微环境中的黏附及定植效率。
