HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Citation Map Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Reprints/Permissions Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Slayton, W. B. Articles by Sola, M. C. Search for Related Content PubMed PubMed Citation Articles by Slayton, W. B. Articles by Sola, M. C.

Developmental Differences in Megakaryocyte Maturation Are Determined by the Microenvironment

^a University of Florida Department of Pediatrics, Gainesville, Florida, USA;
^b Program in Stem Cell Biology and Regenerative Medicine, University of Florida Shands Cancer Center, Gainesville, Florida, USA;
^c The Blood and Marrow Transplant Program, University of Florida, Gainesville, Florida, USA

Key Words. Megakaryocytopoiesis • Thrombopoiesis • Adult bone marrow stem cells • Umbilical cord blood • Development

Correspondence: William B. Slayton, M.D., J. Hillis Miller Health Center, Box 100296, Gainesville, Florida 32610, USA. Telephone: 352-392-5633; Fax: 352-392-2875; e-mail: slaytwb{at}peds.ufl.edu

Historically, physicians have attributed delayed platelet engraftment following umbilical cord blood transplant to decreased numbers of stem cells in cord blood compared with adult bone marrow. However, recent studies suggest that delayed platelet engraftment may be caused by an intrinsic inability of neonatal stem cells to produce mature, polyploid megakaryocytes. We tested this hypothesis by transplanting adult bone marrow and newborn liver hematopoietic stem and progenitor cells from transgenic mice expressing green fluorescent protein into myeloablated wild-type recipients and comparing the size and ploidy levels of megakaryocytes that developed in adult transplant recipients. Transplanted stem and progenitor cells, regardless of their source, gave rise to megakaryocytes that were larger than normal adult megakaryocytes as early as 7 days post-transplant. However, megakaryocytes that developed after transplant of neonatal stem and progenitor cells were significantly smaller than those derived from adult stem and progenitor cells. Furthermore, megakaryocytes derived from neonatal cells had lower ploidy values than megakaryocytes derived from adult cells at 18 days post-transplant, when ploidy could first be reliably measured in the bone marrow. These differences in size and ploidy disappeared by 1 month post-transplant. The largest megakaryocytes developed in the spleen. These results suggest that, in the mouse, the microenvironment is responsible for some of the maturational differences in size and ploidy between neonatal and adult megakaryocytes. Furthermore, neonatal and adult megakaryocyte progenitors also have cell-intrinsic differences in the way they engraft and respond to thrombocytopenic stress. These differences may contribute to the delay in platelet engraftment that frequently complicates cord blood transplants.

This article has been cited by other articles:

				I. S. Hitchcock, N. E. Fox, N. Prevost, K. Sear, S. J. Shattil, and K. Kaushansky Roles of focal adhesion kinase (FAK) in megakaryopoiesis and platelet function: studies using a megakaryocyte lineage specific FAK knockout Blood, January 15, 2008; 111(2): 596 - 604. [Abstract] [Full Text] [PDF]

				K. M. Pastos, W. B. Slayton, L. M. Rimsza, L. Young, and M. C. Sola-Visner Differential effects of recombinant thrombopoietin and bone marrow stromal-conditioned media on neonatal versus adult megakaryocytes Blood, November 15, 2006; 108(10): 3360 - 3362. [Abstract] [Full Text] [PDF]