https://onlinelibrary.wiley.com/doi/pdf/10.1111/j.1538-7836.2007.02472.x

From hematopoietic stem cells to platelets

Developmental differences in megakaryocytopoiesis are associated with up-regulated TPO signaling through mTOR and elevated GATA-1 levels in neonatal megakaryocytes.

Roles of focal adhesion kinase (FAK) in megakaryopoiesis and platelet function: studies using a megakaryocyte lineage–specific FAK knockout

Expansion of the neonatal platelet mass is achieved via an extension of platelet lifespan.

Differential effects of recombinant thrombopoietin and bone marrow stromal-conditioned media on neonatal versus adult megakaryocytes

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.

https://stemcellsjournals.onlinelibrary.wiley.com/doi/pdf/10.1634/stemcells.2004-0373

Anil Jotwani

Papers

Developmental Differences in Megakaryocyte Maturation Are Determined by the Microenvironment

Umbilical cord blood produces small megakaryocytes after transplantation.