Capitano Maegan L, Hangoc Giao, Cooper Scott, Broxmeyer Hal E
Department of Microbiology and Immunology, Indiana University School of Medicine, Indianapolis, Indiana, USA.
Stem Cells. 2015 Jun;33(6):1975-84. doi: 10.1002/stem.1988.
Simple efforts are needed to enhance cord blood (CB) transplantation. We hypothesized that short-term exposure of CD34(+) CB cells to 39.5°C would enhance their response to stromal-derived factor-1 (SDF-1), by increasing lipid raft aggregation and CXCR4 expression, thus leading to enhanced engraftment. Mild hyperthermia (39.5°C) significantly increased the percent of CD34(+) CB that migrated toward SDF-1. This was associated with increased expression of CXCR4 on the cells. Mechanistically, mild heating increased the percent of CD34(+) cells with aggregated lipid rafts and enhanced colocalization of CXCR4 within lipid raft domains. Using methyl-β-cyclodextrin (MβCD), an agent that blocks lipid raft aggregation, it was determined that this enhancement in chemotaxis was dependent upon lipid raft aggregation. Colocalization of Rac1, a GTPase crucial for cell migration and adhesion, with CXCR4 to the lipid raft was essential for the effects of heat on chemotaxis, as determined with an inhibitor of Rac1 activation, NSC23766. Application-wise, mild heat treatment significantly increased the percent chimerism as well as homing and engraftment of CD34(+) CB cells in sublethally irradiated non-obese diabetic severe combined immunodeficiency IL-2 receptor gamma chain d (NSG) mice. Mild heating may be a simple and inexpensive means to enhance engraftment following CB transplantation in patients.
只需采取简单措施就能增强脐血（CB）移植效果。我们推测，将CD34(+)脐血细胞短期暴露于39.5°C，可通过增加脂筏聚集和CXCR4表达来增强其对基质衍生因子-1（SDF-1）的反应，从而提高植入率。轻度热疗（39.5°C）显著增加了向SDF-1迁移的CD34(+)脐血百分比。这与细胞上CXCR4表达增加有关。从机制上讲，轻度加热增加了脂筏聚集的CD34(+)细胞百分比，并增强了CXCR4在脂筏结构域内的共定位。使用甲基-β-环糊精（MβCD），一种阻断脂筏聚集的试剂，确定这种趋化性增强依赖于脂筏聚集。Rac1是一种对细胞迁移和黏附至关重要的GTP酶，它与CXCR4在脂筏中共定位对于热对趋化性的影响至关重要，这是通过Rac1激活抑制剂NSC23766确定的。在应用方面，轻度热处理显著增加了亚致死剂量照射的非肥胖糖尿病严重联合免疫缺陷IL-2受体γ链缺陷（NSG）小鼠中CD34(+)脐血细胞的嵌合率以及归巢和植入率。轻度加热可能是一种简单且廉价的方法，可增强患者脐血移植后的植入效果。
