scholarly journals DNA damage response and preleukemic fusion genes induced by ionizing radiation in umbilical cord blood hematopoietic stem cells

2020 ◽  
Vol 10 (1) ◽  
Author(s):  
Pavol Kosik ◽  
Matus Durdik ◽  
Lukas Jakl ◽  
Milan Skorvaga ◽  
Eva Markova ◽  
...  
Keyword(s):  
Dna Damage ◽  
Ionizing Radiation ◽  
Cord Blood ◽  
Progenitor Cells ◽  
Umbilical Cord ◽  
Umbilical Cord Blood ◽  
Fusion Genes ◽  
Hematopoietic Stem ◽  
Radiation Induced ◽  
Induced Apoptosis

Abstract There is clear evidence that ionizing radiation (IR) causes leukemia. For many types of leukemia, the preleukemic fusion genes (PFG), as consequences of DNA damage and chromosomal translocations, occur in hematopoietic stem and progenitor cells (HSPC) in utero and could be detected in umbilical cord blood (UCB) of newborns. However, relatively limited information is available about radiation-induced apoptosis, DNA damage and PFG formation in human HSPC. In this study we revealed that CD34+ HSPC compared to lymphocytes: (i) are extremely radio-resistant showing delayed time kinetics of apoptosis, (ii) accumulate lower level of endogenous DNA damage/early apoptotic γH2AX pan-stained cells, (iii) have higher level of radiation-induced 53BP1 and γH2AX/53BP1 co-localized DNA double stranded breaks, and (iv) after low dose of IR may form very low level of BCR-ABL PFG. Within CD34+ HSPC we identified CD34+CD38+ progenitor cells as a highly apoptosis-resistant population, while CD34+CD38− hematopoietic stem/multipotent progenitor cells (HSC/MPP) as a population very sensitive to radiation-induced apoptosis. Our study provides critical insights into how human HSPC respond to IR in the context of DNA damage, apoptosis and PFG.

Immunoglobulin gene expression in umbilical cord blood-derived CD34+ hematopoietic stem/progenitor cells

Gene ◽  
2016 ◽  
Vol 575 (1) ◽  
pp. 108-117 ◽  
Author(s):  
Jingfang Liu ◽  
Miaoran Xia ◽  
Pingzhang Wang ◽  
Chong Wang ◽  
Zihan Geng ◽  
...  
Keyword(s):  
Gene Expression ◽  
Cord Blood ◽  
Progenitor Cells ◽  
Umbilical Cord ◽  
Umbilical Cord Blood ◽  
Immunoglobulin Gene ◽  
Hematopoietic Stem

scholarly journals Catalase Inhibits Ionizing Radiation-Induced Apoptosis in Hematopoietic Stem and Progenitor Cells

2015 ◽  
Vol 24 (11) ◽  
pp. 1342-1351 ◽  
Author(s):  
Xia Xiao ◽  
Hongmei Luo ◽  
Kenneth N. Vanek ◽  
Amanda C. LaRue ◽  
Bradley A. Schulte ◽  
...  
Keyword(s):  
Ionizing Radiation ◽  
Progenitor Cells ◽  
Hematopoietic Stem ◽  
Stem And Progenitor Cells ◽  
Radiation Induced ◽  
Induced Apoptosis

scholarly journals MicroRNA-21 over expression in umbilical cord blood hematopoietic stem progenitor cells by leukemia microvesicles

2019 ◽  
Vol 42 (2) ◽  
pp. 465-471 ◽  
Author(s):  
Farnaz Razmkhah ◽  
Masoud Soleimani ◽  
Sorayya Ghasemi ◽  
Sedigheh Amini Kafi-abad
Keyword(s):  
Cord Blood ◽  
Progenitor Cells ◽  
Umbilical Cord ◽  
Umbilical Cord Blood ◽  
Hematopoietic Stem ◽  
Over Expression

Study of In Vitro Proliferation Potential of CD133 Positive Cells Derived from Umbilical Cord Blood.

Blood ◽  
2007 ◽  
Vol 110 (11) ◽  
pp. 4039-4039
Author(s):  
Ri Zhang ◽  
Wenjin Gao ◽  
Yuanyuan Sun ◽  
Jingcheng Miao ◽  
Xueguang Zhang
Keyword(s):  
Cord Blood ◽  
Progenitor Cells ◽  
Umbilical Cord ◽  
Umbilical Cord Blood ◽  
Ex Vivo ◽  
Ex Vivo Expansion ◽  
Hematopoietic Stem ◽  
Low Concentration ◽  
Tgf Β1

Abstract Transforming growth factor-beta 1 (TGF-β1) is known to maintain primitive human hematopoietic stem/progenitor cells with polyfunctional role in a quiescent state and CD133 is a new stem cell antigen that may provide an alternative to CD34 for the selection and expansion of hematopoietic cells for transplantation. To investigate the specific effect of TGF-β1 on proliferation and differentiation of CD133 positive cells derived from umbilical cord blood (UCB) during short-term culture in vitro, CD133 positive cells from 20 fresh UCB samples were selected using Miltenyi Biotec’s CliniMACS separation device and were cultured in IMDM medium with 20% FCS in the presence of a cytokine combination of SCF, IL-6, thrombopoietin, IL-3 and Flt3-ligand for up to 2 weeks and TGF-β1 with low concentration was also added to the mediumon day 4. The proliferative response was assessed at day 7, day 10 and day 14 by evaluating the following parameters: nucleated cells (NC), clonogenic progenitors (CFU-GEMM,CFU-GM and BFU-E), and immunophenotypes (CD133 and CD34). The results showed that efficacious expansion of various hematopoietic stem/progenitor cells was constantly observed during the culture. The fold expansion of NC on day7, day10 and day14 expansion were 33.59,224.26 and 613.48, respectively. The fold expansion of CFU-GEMM, CFU-GM and BFU-E on day 10 were 24.89, 41.62 and 49.28, respectively, obviously higher than that without ex vivo expansion (P<0.05). The expansions of CD133+, CD133+CD34+ and CD34+ subpopulation on day 14 were up to 25.83-fold, 16.16-fold and 60.54-fold, respectively. Furthermore the expansion systems with TGF-β1 showed more CD133+ cells than control at every time points. Our datas suggested that the CD133+ cells from human UCB have great expansion potential for ex-vivo expansion. The low concentration of TGF-β1 may delay over-differentiation of hematopoietic stem/progenitor cells.

Identification of functional endothelial progenitor cells suitable for the treatment of ischemic tissue using human umbilical cord blood

Blood ◽  
2007 ◽  
Vol 110 (1) ◽  
pp. 151-160 ◽  
Author(s):  
Masumi Nagano ◽  
Toshiharu Yamashita ◽  
Hiromi Hamada ◽  
Kinuko Ohneda ◽  
Ken-ichi Kimura ◽  
...  
Keyword(s):  
Stem Cells ◽  
Cord Blood ◽  
Progenitor Cells ◽  
Endothelial Progenitor Cells ◽  
Umbilical Cord ◽  
Umbilical Cord Blood ◽  
Human Umbilical Cord ◽  
Aldh Activity ◽  
Endothelial Progenitor ◽  
Hematopoietic Stem

Umbilical cord blood (UCB) has been used as a potential source of various kinds of stem cells, including hematopoietic stem cells, mesenchymal stem cells, and endothelial progenitor cells (EPCs), for a variety of cell therapies. Recently, EPCs were introduced for restoring vascularization in ischemic tissues. An appropriate procedure for isolating EPCs from UCB is a key issue for improving therapeutic efficacy and eliminating the unexpected expansion of nonessential cells. Here we report a novel method for isolating EPCs from UCB by a combination of negative immunoselection and cell culture techniques. In addition, we divided EPCs into 2 subpopulations according to the aldehyde dehydrogenase (ALDH) activity. We found that EPCs with low ALDH activity (Alde-Low) possess a greater ability to proliferate and migrate compared to those with high ALDH activity (Alde-High). Moreover, hypoxia-inducible factor proteins are up-regulated and VEGF, CXCR4, and GLUT-1 mRNAs are increased in Alde-Low EPCs under hypoxic conditions, while the response was not significant in Alde-High EPCs. In fact, the introduction of Alde-Low EPCs significantly reduced tissue damage in ischemia in a mouse flap model. Thus, the introduction of Alde-Low EPCs may be a potential strategy for inducing rapid neovascularization and subsequent regeneration of ischemic tissues.

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