Umbilical Cord Blood Produces Small Megakaryocytes After Transplantation

Abstract

Delayed platelet engraftment is a major complication of umbilical cord blood (CB) transplantation. Megakaryocytes derived from CB in vitro are smaller than megakaryocytes derived from bone marrow (BM) or mobilized peripheral blood from adults. Small megakaryocyte size may contribute to delayed platelet engraftment. To test whether small size persists after transplantation, we measured megakaryocyte size, concentration, and maturational stage in BM biopsy specimens obtained after transplantation in archived BM samples from patients receiving CB (CB group, n = 10) versus mobilized peripheral blood or BM transplantation (BM group, n = 9). Megakaryocytes in the postengraftment BM samples were significantly smaller in the CB group than in the BM group (median diameter, 16.7 vs 22.0 microm). There were no significant differences in megakaryocyte concentration or maturational stage between the CB and BM groups. For the first time, we demonstrate that the attainment of adult size in CB-derived megakaryocytes is delayed after human CB transplantation.

Evaluation of human cord blood CD34+ hematopoietic stem cell differentiation to megakaryocyte on aminated PES nanofiber scaffold compare to 2-D culture system

“…Regardless of the abundant advantages of using UCB for transplantation compared to other cell sources, the low number of HSPCs contained in a single UCB unit, and the consequently delayed platelet recovery, has limited successful transplantation (Laughlin 2001, Koh et al 2007). Platelet recovery in cord blood (CB) transplantation takes a longer period compared to that in bone marrow (BM) or mobilized peripheral blood (MPB) cell transplantation (Chen et al 2009), as the average of number of days for platelet engraftment in UCB and MPB is nearly 70 and 20 days, respectively (Ignatz et al 2007). Th us, ex vivo expansion of megakaryocytes (Mk) derived from UCB along with HSCs might accelerate Mk diff erentiation and platelet recovery after transplantation.…”

Neonatal expression of RNA-binding protein IGF2BP3 regulates the human fetal-adult megakaryocyte transition

“…Thus, transplant recipients of neonatal, cord blood-derived hematopoietic stem and progenitor cells (CB HSPCs) have smaller megakaryocytes and slower platelet recovery compared with age-matched recipients of adult HSPCs, despite having equal megakaryocyte numbers (7). In ex vivo HSPC cultures, CB megakaryocytes show a greater than 10-fold enhancement in proliferation and markedly diminished morphogenesis compared with adult counterparts (8).…”

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

“…This is supported by the finding that CB-derived MKs remain significantly smaller than those derived from adult sources for at least 3 months after transplantation. 14 The small size of neonatal MKs is also thought to contribute to the high incidence of thrombocytopenia among sick premature neonates. 8,15 Although megakaryocytopoiesis is regulated by multiple cytokines, TPO is the main stimulatory factor for MK proliferation and maturation.…”