All‐trans retinoic acid prevents apoptosis of human marrow CD34⁺ cells deprived of haematopoietic growth factors

Abstract

Summary. The regulation of apoptosis plays a key role in haematopoiesis. It has been demonstrated that haematopoietic progenitor cells progressively undergo apoptotic cell death in the absence of appropriate growth factors. We studied the effects of pharmacological doses of all-trans retinoic acid (ATRA) on the apoptosis of human adult marrow CD34 + progenitor cells cultured for 7 d in a serum-free medium. We quantified CD34 + cells, clonogenic progenitors and 5 week colony-forming cells (CFC) before and after ATRA exposure. Moreover, we defined the apoptotic status of the CD34 + cell fraction by analysis of phosphatidylserine externalization (using annexin V), the relative membrane permeability to 7-aminoactinomycin D (7AAD) and the mitochondrial membrane potential [using 3,3¢-dihexyloxacarbocyanine iodide, DiOC 6 (3)]. In the drastic experimental conditions used, a decrease in viable CD34 + cells, granulocyte-macrophage colony-forming units (CFU-GM), erythroid burst-forming units (BFU-E) and 5 week CFC were observed. Exposure to ATRA partially prevented the decrease in viable CD34 + , without a concomitant effect on the clonogenic and more immature progenitors. ATRAtreated CD34 + cells displayed changes in apoptotic status compared with control cultures, particularly in lower annexin V-binding. These results were confirmed using 7AAD and DiOC 6 (3). Our results demonstrate that ATRA exerts a protective effect on CD34 + cells exposed to such apoptotic stress.

Erythropoiesis in HIV-infected and uninfected Malawian children with severe anemia

“…The African HIV-IC subtype can directly infect CD34+ hematopoietic progenitors[23]. Unlike previous studies[24,25] we found no association between dyserythropoiesis or apoptosis and altered cytokine levels or vitamin A deficiency[26,27], despite 90% of children having vitamin A deficiency[14]. More intensive investigations might identify cytokines that affect regulatory signals and could potentially be therapeutic targets to reduce hemopoietic inhibition in HIV patients.…”

Retinoic acid‐mediated induction of neurons and glial cells from human umbilical cord‐derived hematopoietic stem cells

“…In the present study, however, we found that nestin expression in cord blood‐derived CD133 + cells increased with RA treatment. RA has been involved not only in embryonic development and neurogenesis (Niederreither et al, 2002) but also in survival of human bone marrow CD34 + cells in the absence of hematopoietic growth factors (Herault et al, 2002). Therefore, it is plausible that in the present study, RA played important roles in maintaining self‐renewal ability and promoting differentiation of hematopoietic stem cells to neural progenitor cells.…”

Sertraline increases the survival of retinoic acid induced neuronal cells but not glial cells from human mesenchymal stem cells

“…RA also induces differentiation of embryonic stem cells into other types, including astrocytes, lung (Malpel et al, ), kidney (Mendelsohn et al, ), intestine (Plateroti et al, ), urothelium (Mauney et al, ), and pancreas (Micallef et al, ) in a time‐ and concentration‐dependent manner (Schuldiner et al, ). RA can maintain the survival of human bone marrow CD34‐positive cells in the absence of hematopoietic growth factors (Herault et al, ).…”