Nicotinamide Boots Magakaryocytic Cells in CD34+ Cells

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British Journal of Haematology

Volume 135 Page 554 - November 2006

doi:10.1111/j.1365-2141.2006.06341.x

Volume 135 Issue 4

research paper

Nicotinamide (vitamin B3) increases the polyploidisation and

proplatelet formation of cultured primary human megakaryocytes

M. Giammona1, G. Fuhrken1, Eleftherios T. Papoutsakis1,2

and M. 1,2

Summary

Megakaryocytic (Mk) cell maturation involves polyploidisation, and the

number of platelets produced increases with Mk DNA content. Ploidy

levels in cultured human MK cells are much lower than those observed

in vivo.

This study demonstrated that adding the water-soluble vitamin

nicotinamide (NIC) to mobilised peripheral blood CD34+ cells cultured

with thrombopoietin (Tpo) more than doubled the percentage of

high-ploidy ( & #8805;8N) MK cells. This was observed regardless of

donor-dependent differences in Mk differentiation. Furthermore, MK

cells in cultures with NIC were larger, had more highly lobated

nuclei, reached a maximum DNA content of 64N (vs. 16N with Tpo alone),

and exhibited more frequent and more elaborate cytoplasmic extensions.

NIC also increased the ploidy of cultured primary murine MK cells and

a cell line model (CHRF-288) of Mk differentiation.

However, NIC did not alter Mk commitment, apoptosis, or the time at

which endomitosis was initiated.

Despite the dramatic phenotypic differences observed with NIC

addition, gene expression microarray analysis revealed similar overall

transcriptional patterns in primary human Mk cultures with or without

NIC, indicating that NIC did not disrupt the normal Mk transcriptional

program.

Elucidating the mechanisms by which NIC increases Mk maturation could

lead to advances in the treatment of Mk and platelet disorders.