National Centre for Cell Science, NCCS Complex, Savitribai Phule Pune University Campus, Pune 411007, India.
Chemical Biology Unit, Division of Organic Chemistry, CSIR-National Chemical Laboratory, Dr. Homi Bhabha Road, Pune 411008, India.
J Nutr Biochem. 2017 Sep;47:94-105. doi: 10.1016/j.jnutbio.2017.05.002. Epub 2017 May 17.
Hematopoietic stem cells play the vital role of maintaining appropriate levels of cells in blood. Therefore, regulation of their fate is essential for their effective therapeutic use. Here we report the role of polyunsaturated fatty acids (PUFAs) in regulating hematopoiesis which has not been explored well so far. Mice were fed daily for 10 days with n-6/n-3 PUFAs, viz. linoleic acid (LA), arachidonic acid (AA), alpha-linolenic acid and docosahexanoic acid (DHA) in four separate test groups with phosphate-buffered saline fed mice as control set. The bone marrow cells of PUFA-fed mice showed a significantly higher hematopoiesis as assessed using side population, Lin-Sca-1ckit+, colony-forming unit (CFU), long-term culture, CFU-spleen assay and engraftment potential as compared to the control set. Thrombopoiesis was also stimulated in PUFA-fed mice. A combination of DHA and AA was found to be more effective than when either was fed individually. Higher incorporation of PUFAs as well as products of their metabolism was observed in the bone marrow cells of PUFA-fed mice. A stimulation of the Wnt, CXCR4 and Notch1 pathways was observed in PUFA-fed mice. The clinical relevance of this study was evident when bone marrow-transplanted recipient mice, which were fed with PUFAs, showed higher engraftment of donor cells, suggesting that the bone marrow microenvironment may also be stimulated by feeding with PUFAs. These data indicate that oral administration of PUFAs in mice stimulates hematopoiesis and thrombopoiesis and could serve as a valuable supplemental therapy in situations of hematopoietic failure.
造血干细胞在维持血液中细胞的适当水平方面发挥着至关重要的作用。因此，调节其命运对于其有效治疗应用至关重要。本文报道了多不饱和脂肪酸（PUFAs）在调节造血作用方面的作用，迄今为止这方面尚未得到充分探索。将 n-6/n-3 PUFAs（即亚油酸（LA）、花生四烯酸（AA）、α-亚麻酸和二十二碳六烯酸（DHA））分别喂饲给 4 组实验小鼠，每日 1 次，连续 10 天，同时以磷酸盐缓冲盐水喂饲的小鼠作为对照组。与对照组相比，用侧群、Lin-Sca-1ckit+、集落形成单位（CFU）、长期培养、CFU-脾测定和植入潜能评估的方法，发现 PUFAs 喂养的小鼠骨髓细胞的造血作用明显增强。PUFAs 喂养的小鼠也刺激了血小板生成。发现 DHA 和 AA 的组合比单独喂食任何一种都更有效。在 PUFAs 喂养的小鼠的骨髓细胞中观察到更高的 PUFAs 及其代谢产物的掺入。在 PUFAs 喂养的小鼠中观察到 Wnt、CXCR4 和 Notch1 途径的刺激。当用 PUFAs 喂养骨髓移植的受体小鼠时，这项研究的临床相关性变得明显，因为这些受体小鼠的供体细胞的植入率更高，这表明骨髓微环境也可能受到 PUFAs 喂养的刺激。这些数据表明，在小鼠中口服 PUFAs 可刺激造血和血小板生成，并且可以作为造血衰竭情况下的有价值的补充治疗方法。
