Oral feeding with polyunsaturated fatty acids fosters hematopoiesis and thrombopoiesis in healthy and bone marrow-transplanted mice |
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| Institution: | 1. National Centre for Cell Science, NCCS Complex, Savitribai Phule Pune University Campus, Pune 411007, India;2. Chemical Biology Unit, Division of Organic Chemistry, CSIR-National Chemical Laboratory, Dr. Homi Bhabha Road, Pune 411008, India;3. CSIR-Institute of Genomics and Integrative Biology, Mall Road, New Delhi 110007, India;1. Department of Molecular and Life Sciences, Hanyang University, Ansan, Republic of Korea;2. Institute of Natural Science and Technology, Hanyang University, Ansan, Republic of Korea;3. Department of Bionanotechnology, Hanyang University, Seoul, Republic of Korea;1. Department of Pediatrics, Medical College of Wisconsin, Milwaukee, WI, USA;2. Children''s Research Institute, Medical College of Wisconsin, Milwaukee, WI, USA;3. Blood Research Institute, Blood Center of Wisconsin, Milwaukee, WI, USA;4. Department of Biophysics, Medical College of Wisconsin, Milwaukee, WI, USA;5. Department of Mechanical Engineering, University of Connecticut, Storrs, CT, USA;6. Department of Chemistry, Purdue University, West Lafayette, IN, USA;7. Technical Services, Harlan-Teklad Laboratories, Inc., Madison, WI, USA |
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| Abstract: | 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-1+ckit+, 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. |
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