Cytochrome P450 (CYP) enzymes metabolize numerous endogenous substrates, such as retinoids, androgens, estrogens and vitamin D, that can modulate important cellular processes, including proliferation, differentiation and apoptosis. The aim of this study is to characterize the expression of CYP genes in CD34+ human cord blood hematopoietic stem and early progenitor cells (CBHSPCs) as a first step toward assessment of the potential biological functions of CYP enzymes in regulating the expansion or differentiation of these cells. CD34+ CBHSPCs were purified from umbilical cord blood via antibody affinity chromatography. Purity of CD34+ CBHSPCs was assessed using fluorescence-activated cell sorting. RNA was isolated from purified CD34+ CBHSPCs and total mononuclear cells (MNCs) for RNA-PCR analysis of CYP expression. Fourteen human CYPs were detected in the initial screening with qualitative RT-PCR in CD34+ CBHSPCs. Further quantitative RNA-PCR analysis of the detected CYP transcripts yielded evidence for preferential expression of CYP2R1 in CD34+ CBHSPCs relative to MNCs; and for greater expression of CYP1B1 in MNCs relative to CD34+ CBHSPCs. These findings provide the basis for further studies on possible functions of CYP2R1 and CYP1B1 in CBHSPCs׳ proliferation and/or differentiation and their potential utility as targets for drugs designed to modulate CD34+ CBHSPC expansion or differentiation.
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http://dx.doi.org/10.1016/j.apsb.2014.10.003 | DOI Listing |
Mol Biotechnol
April 2024
Gene Therapy and Regenerative Medicine Research Center, Hope Generation Foundation, University of Social Welfare and Rehabilitation Sciences, No. 44 South Africa Blvd, PO Box, Tehran, 15178-85316, Iran.
Reactivation of the fetal hemoglobin (HbF) in adult erythroid cells via genome editing is a strategy for the treatment of β-thalassemia and sickle cell disease. In related reports, the reactivation of HbF is regularly examined in erythroblasts which are generated from the adult CD34 hematopoietic stem and progenitor cells (HSPCs). However, the procurement of adult HSPCs, either from the bone-marrow (BM) or from mobilized peripheral-blood (mPB), is difficult.
View Article and Find Full Text PDFStem Cells Transl Med
November 2021
Stem Cells and Regenerative Medicine Lab, Institute of Health Service and Transfusion Medicine, Beijing, People's Republic of China.
Red blood cells (RBCs) and platelets derived from stem cells are possible solutions to the increasing demand for blood transfusion. Based on the availability of stem cells, their relatively defined differentiation mechanisms, and the massive exploration of induction systems, the generation of RBCs or platelets in vitro from cord blood hematopoietic stem/progenitor cells (CB-HSPCs) has potential for clinical applications. However, information on the clinical translation of stem cell-derived RBCs and platelets in the literature and at the ClinicalTrials.
View Article and Find Full Text PDFLeukemia
October 2021
Department of Cell Biology, Faculty of Biochemistry, Biophysics and Biotechnology, Jagiellonian University, Krakow, Poland.
Cord blood (CB) represents a source of hematopoietic stem and progenitor cells (CB-HSPCs) for bone marrow (BM) reconstitution, but clinical CB application is limited in adult patients due to the insufficient number of CB-HSCPCs and the lack of effective ex vivo approaches to increase CB-HSPC functionality. Since human-induced pluripotent stem cells (hiPSCs) have been indicated as donor cells for bioactive extracellular vesicles (EVs) modulating properties of other cells, we are the first to employ hiPSC-derived EVs (hiPSC-EVs) to enhance the hematopoietic potential of CB-derived CD45LinCD34 cell fraction enriched in CB-HSPCs. We demonstrated that hiPSC-EVs improved functional properties of CB-HSPCs critical for their hematopoietic capacity including metabolic, hematopoietic and clonogenic potential as well as survival, chemotactic response to stromal cell-derived factor 1 and adhesion to the model components of hematopoietic niche in vitro.
View Article and Find Full Text PDFLife Sci
March 2021
Institute of Biomedical Problems, Russian Academy of Sciences, Moscow, Russia.
Aims: Stroma-dependent ex vivo expansion of hematopoietic stem progenitor cells (HSPCs) is a valid approach for cell therapy needs. Our goal was to verify whether HSPCs can affect stromal cells to optimize their functions during ex vivo expansion.
Main Methods: HSPCs from cord blood (cb) were cocultured with growth-arrested adipose mesenchymal stromal cells (MSCs).
Am J Hematol
August 2018
Laboratory of Developmental Erythropoiesis, Center for Autoimmune, Musculoskeletal, and Hematopoietic Diseases, The Feinstein Institute for Medical Research, Manhasset, New York, 11030.
Studies of human erythropoiesis have relied, for the most part, on the in vitro differentiation of hematopoietic stem and progenitor cells (HSPC) from different sources. Here, we report that despite the common core erythroid program that exists between cord blood (CB)- and peripheral blood (PB)-HSPC induced toward erythroid differentiation in vitro, significant functional differences exist. We undertook a comparative analysis of human erythropoiesis using these two different sources of HSPC.
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