title: Arachidonic acid and Docosahexanoic acid enhance platelet formation from human apheresis-derived CD34+cells.
abstract: An Aberration in megakaryopoiesis and thrombopoiesis, 2 important processes that maintain hemostasis, leads to thrombocytopenia. Though platelet transfusions are used to treat this condition, blood banks frequently face a shortage of platelets. Therefore, methods to generate platelets on a large scale are strongly desirable. However, to generate megakaryocytes (MKs) and platelets (PLTs) in numbers sufficient for clinical application, it is essential to understand the mechanism of platelet production and explore efficient strategies accordingly. We have earlier reported that the N-6 and N-3 poly-unsaturated fatty acids (PUFAs), Arachidonic acid (AA)/Docosahexanoic acid (DHA) have beneficial effect on the generation of MKs and PLTs from umbilical cord blood derived CD34+cells. Here we tested if a similar effect is observed with peripheral blood derived CD34+cells, which are more commonly used in transplantation settings. We found a significant enhancement in cell numbers, surface marker expression, cellular ploidy and expression of cytoskeletal components during PLT biogenesis in cultures exposed to media containing AA/DHA than control cultures that were not exposed to these PUFAs. The test cells engrafted more efficiently in NOD/SCID mice than control cells. AA/DHA appears to have enhanced MK/PLT generation through upregulation of the NOTCH and AKT pathways. Our data show that PUFAs could be valuable additives in the culture system for large scale production of platelets for clinical applications.
authors.affiliation: a National Centre for Cell Science, NCCS Complex, Savitribai Phule Pune University Campus , Pune , India.
authors.forename: Ankita
authors.initials: A
authors.lastname: Dhenge
authors.affiliation: a National Centre for Cell Science, NCCS Complex, Savitribai Phule Pune University Campus , Pune , India.
authors.forename: Kedar
authors.initials: K
authors.lastname: Limbkar
authors.affiliation: b Blood and Marrow Transplant Unit, Deenanath Mangeshkar Hospital , Pune , India.
authors.forename: Sameer
authors.initials: S
authors.lastname: Melinkeri
authors.affiliation: a National Centre for Cell Science, NCCS Complex, Savitribai Phule Pune University Campus , Pune , India.
authors.forename: Vaijayanti Prakash
authors.initials: VP
authors.lastname: Kale
authors.affiliation: a National Centre for Cell Science, NCCS Complex, Savitribai Phule Pune University Campus , Pune , India.
authors.forename: Lalita
authors.initials: L
authors.lastname: Limaye
mesh_terms: D000818:Animals; D018952:Antigens, CD34 / Q000235:genetics; D016718:Arachidonic Acid / Q000494:pharmacology*; D001781:Blood Component Removal; D001792:Blood Platelets / Q000166:cytology* / Q000187:drug effects; D002454:Cell Differentiation / Q000187:drug effects; D019070:Cell Lineage / Q000187:drug effects; D004281:Docosahexaenoic Acids / Q000494:pharmacology*; D005312:Fetal Blood / Q000166:cytology / Q000187:drug effects; D006801:Humans; D008533:Megakaryocytes / Q000166:cytology / Q000187:drug effects*; D051379:Mice; D017713:Platelet Transfusion; D015398:Signal Transduction / Q000187:drug effects; D034061:Thrombopoiesis / Q000187:drug effects
chemical_list: D018952:Antigens, CD34; D004281:Docosahexaenoic Acids; D016718:Arachidonic Acid
keywords: megakaryocytes; mobilized peripheral blood; platelets and polyunsaturated fatty acids and differentiation