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Application of mutant JAK2V617F for in vitro generation of red blood cells.
- Source :
-
Transfusion . Apr2016, Vol. 56 Issue 4, p837-843. 7p. - Publication Year :
- 2016
-
Abstract
- <bold>Background: </bold>In vitro generation of red blood cells (RBCs) from hematopoietic stem cells (HSCs) has been reported, but the collection of 1 × 10(5) to 1 × 10(6) CD34+ cells present in cord and peripheral blood is too small for expansion to 1 × 10(12) cells in 1 unit of RBCs. We transduced JAK2V617F gene, the most common mutation with polycythemia vera (PV), into cord blood-derived CD34+ cells. This PV model was expected to increase cell proliferation without the addition of erythropoietin (EPO) in early phase of differentiation.<bold>Study Design and Methods: </bold>Empty vector (control), wild-type JAK2 (wJAK2), and mutant JAK2V617F (mJAK2) were transduced into CD34+ cells using a lentivirus system. The CD34+ cells were then differentiated to the RBCs in a culture system. The cells were analyzed for cell number, differential count, and morphologic changes. Cultured RBCs were tested for oxygen equilibrium.<bold>Results: </bold>wJAK2- and mJAK2-transduced cells showed higher proliferation capacity until Day 21 than control cells; interestingly, only mJAK2-transduced cells were highly increased on Day 7 during EPO-free culture. However, both wJAK2- and mJAK2-tranduced cells had more delayed differentiation than control, but they had a higher portion of completely matured RBCs and orthochromatic erythroblasts. Furthermore, mJAK2-tranduced cells showed more differentiation into RBCs than wJAK2-transduced cells and they had a normal hemoglobin dissociation curve.<bold>Conclusion: </bold>This is the first trial to use a PV erythropoiesis model for RBC differentiation from stem cells. The transduction of HSCs with mJAK2 increased their proliferation capacity in EPO-free culture conditions. This model may also be useful for investigating the pathogenesis of PV. [ABSTRACT FROM AUTHOR]
Details
- Language :
- English
- ISSN :
- 00411132
- Volume :
- 56
- Issue :
- 4
- Database :
- Academic Search Index
- Journal :
- Transfusion
- Publication Type :
- Academic Journal
- Accession number :
- 114538780
- Full Text :
- https://doi.org/10.1111/trf.13431