Increased megakaryopoiesis in cultures of CD34‐enriched cord blood cells maintained at 39°C

Abstract

Based on previous evidence suggesting positive effects of fever on in vivo hematopoiesis, we tested the effect of hyperthermia on megakaryopoiesis (MK) in ex vivo cultures of CD34-enriched cord blood (CB) cells. The cells were cultured at 37jC or 39jC for 14 days in cytokine conditions optimized for megakaryocyte development and analyzed periodically. Compared to 37jC, the cultures maintained at 39jC produced significantly more (up to 10-fold) total cells, myeloid and MK progenitors, and total MKs, and showed accelerated and enhanced MK maturation with increased yields of proplatelets and platelets. This observation could facilitate clinical applications requiring ex vivo expansion of hematopoietic cells. B 2004 Wiley Periodicals, Inc.

Glycoprotein Ibα Receptor Instability Is Associated with Loss of Quality in Platelets Produced in Culture

“…GM6001 was added at day 12 following preliminary experiments showing no beneficial effect on GPIba expression when added at earlier time (data not shown). Cultures were maintained in a humidified atmosphere (10% CO 2 , 20% O 2 ) at 398C and 378C for the first and last 7 days of culture, respectively, to increase Mk and PLP yields [9,18]. Viable nucleated cells were manually counted as described [7].…”

“…Megakaryocyte (Mk) and platelet production have been described from different sources of cells such as cell lines [1], embryonic stem cell [2,3], and hematopoietic stem cells [4][5][6][7][8] maintained in suspension cultures [4,5,7,9], or with feeder layers [2,3,6] or in bioreactors [8] (recently reviewed in [10]). Despite many efforts, platelet-like particles' (PLP) yield remains the Achilles' heel of all protocols described to date.…”

Mild Hyperthermia Promotes and Accelerates Development and Maturation of Erythroid Cells

“…Thus, the strong impact on erythropoiesis reported herein is a direct consequence of MH. Consistent with this, several investigations have shown that the temperature of incubation can impact the growth and differentiation of primary bone marrow cells [20,[33][34][35].…”

“…In line with the impact of WBH on platelet levels, we previously demonstrated that expansion and differentiation of cord blood (CB) CD34 + cells along the megakaryocytic (MK) lineage were significantly increased under MH (ie, 39°C) [20]. MH-mediated acceleration of MK differentiation and maturation was shown to be rapid [21], associated with increased levels of the heat shock protein HSP70 [20] and of several transcription factors implicated in erythroid and megakaryocyte differentiation [21].…”

“…MH-mediated acceleration of MK differentiation and maturation was shown to be rapid [21], associated with increased levels of the heat shock protein HSP70 [20] and of several transcription factors implicated in erythroid and megakaryocyte differentiation [21]. Given that the erythroid and MK lineages are closely related, we have investigated herein whether erythropoiesis could also be promoted when CB CD34 + cells are induced to undergo erythroid differentiation under MH.…”