Combined mild hypoxia and bone marrow mesenchymal stem cells improve expansion and HOXB4 gene expression of human cord blood CD34+ stem cells

Mohammadali, Fatemeh; Abroun, Saeid; Atashi, Amir

doi:10.2298/abs171028003m

Cited by 10 publications

(12 citation statements)

References 42 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Mesenchymal stromal cells (MSC) play an important role in the regulation of most cells of the BM microenvironment . From a therapeutic perspective, the administration of MSC has been shown to increase the engraftment ability and the hematopoietic function in preclinical models of xenotransplantation . In addition, it has been shown that the administration of MSC from third‐party donors can also potentially increase the engraftment and improve post‐transplant cytopenias .…”

Section: Introductionmentioning

confidence: 99%

The Incorporation of Extracellular Vesicles from Mesenchymal Stromal Cells Into CD34+ Cells Increases Their Clonogenic Capacity and Bone Marrow Lodging Ability

et al. 2019

View full text Add to dashboard Cite

Mesenchymal stromal cells (MSC) may exert their functions by the release of extracellular vesicles (EV). Our aim was to analyze changes induced in CD34 + cells after the incorporation of MSC-EV. MSC-EV were characterized by flow cytometry (FC), Western blot, electron microscopy, and nanoparticle tracking analysis. EV incorporation into CD34 + cells was confirmed by FC and confocal microscopy, and then reverse transcription polymerase chain reaction and arrays were performed in modified CD34 + cells. Apoptosis and cell cycle were also evaluated by FC, phosphorylation of signal activator of transcription 5 (STAT5) by WES Simple, and clonal growth by clonogenic assays. Human engraftment was analyzed 4 weeks after CD34 + cell transplantation in nonobese diabetic/severe combined immunodeficient mice. Our results showed that MSC-EV incorporation induced a downregulation of proapoptotic genes, an overexpression of genes involved in colony formation, and an activation of the Janus kinase (JAK)-STAT pathway in CD34 + cells. A significant decrease in apoptosis and an increased CD44 expression were confirmed by FC, and increased levels of phospho-STAT5 were confirmed by WES Simple in CD34 + cells with MSC-EV. In addition, these cells displayed a higher colony-forming unit granulocyte/macrophage clonogenic potential. Finally, the in vivo bone marrow lodging ability of human CD34 + cells with MSC-EV was significantly increased in the injected femurs. In summary, the incorporation of MSC-EV induces genomic and functional changes in CD34 + cells, increasing their clonogenic capacity and their bone marrow lodging ability. STEM CELLS 2019;37:1357-1368 SIGNIFICANCE STATEMENTIn the current study, the authors validate for the first time that preincubating human CD34 + cells with extracellular vesicles derived from human mesenchymal stromal cells not only modifies the gene expression of the recipient cells (inducing a downregulation of proapoptotic genes and overexpression of genes involved in colony formation and JAK-STAT pathway) but also significantly increases their in vitro clonogenic ability and, most importantly, increases their 4-week bone marrow lodging ability in vivo in a standard xenotransplantation model. This strategy could potentially be exploited to increase the hematopoietic engraftment in the clinical setting.

show abstract

Section: Introductionmentioning

confidence: 99%

The Incorporation of Extracellular Vesicles from Mesenchymal Stromal Cells Into CD34+ Cells Increases Their Clonogenic Capacity and Bone Marrow Lodging Ability

et al. 2019

View full text Add to dashboard Cite

show abstract

“…Since HSCs are deemed to grow in hypoxic environment (Takubo et al, 2010), low oxygen also plays an important role in the in vitro expansion of HSC. Under the condition of hypoxia, the expression of CXCR4 statistically increased, which means the ability of homing increased (Mohammadali et al, 2018). The use of p38-MAPK inhibitor (Bari et al, 2018) or antioxidants can maintain low ROS levels, protect HSCs from oxidative stress, and inhibit cell aging and differentiation (Ludin et al, 2014;Cao et al, 2016;Testa et al, 2016).…”

Section: Discussionmentioning

confidence: 99%

Antioxidant Small Molecule Compound Chrysin Promotes the Self-Renewal of Hematopoietic Stem Cells

Zhang

et al. 2020

Front. Pharmacol.

View full text Add to dashboard Cite

There is an increasing demand for the expansion of functional human hematopoietic stem cells (hHSCs) for various clinical applications. Based on our primary screening of antioxidant small molecule compounds library, a small molecule compound C2968 (chrysin) was identificated to expand cord blood CD34 + cells in vitro. Then we further verified the optimum concentration and explored its effect on hHSCs phenotype and biological function. C2968 could significantly increase the proportion and absolute number of CD34 + CD38 − CD49f + and CD34 + CD38 − CD45RA − CD90 + cells under 2.5 mM. Furthermore, the total number of colony-forming units and the frequency of LT-HSCs in C2968-treated group were significantly higher than control, indicating the multipotency and long-term activity of hematopoietic stem and progenitor cells were sustained. Additionally, C2968 treatment could maintain transplantable HSCs that preserve balanced multilineage potential and promote rapid engraftment after transplantation in immunodeficient (NOG) mice. Mechanistically, the activity of chrysin might be mediated through multiple mechanisms namely delaying HSC differentiation, inhibiting ROS-activated apoptosis, and modulating of cyclin-dependent kinase inhibitors. Overall, chrysin showed good ex vivo expansion effect on hHSCs, which could maintain the self-renewal and multilineage differentiation potential of hHSCs. Through further research on its antioxidant mechanism, it may become a promising tool for further fundamental research and clinical umbilical cord blood transplantation of hHSCs.

show abstract

“…They have strong proliferation and differentiation ability and can be multi-directionally differentiated into osteoblasts, chondrocytes, hematopoietic cells, muscle cells and other types of cells. They can be used to repair tissue and organ damage (Saito et al, 2018;Mohammadali, Abroun & Atashi, 2018). They have a hematopoietic support function, since they not only provide mechanical support for hematopoietic stem cells in the bone marrow but also secrete a variety of growth factors, such as interleukin (IL)-6, IL-11, leukemia inhibitory factor (LIF), macrophage colony-stimulating factor (M-CSF) and human stem cell growth factor (SCF), to support hematopoiesis (Amini et al, 2018;Mohammadali, Abroun & Atashi, 2018).…”

Section: Discussionmentioning

confidence: 99%

“…They can be used to repair tissue and organ damage (Saito et al, 2018;Mohammadali, Abroun & Atashi, 2018). They have a hematopoietic support function, since they not only provide mechanical support for hematopoietic stem cells in the bone marrow but also secrete a variety of growth factors, such as interleukin (IL)-6, IL-11, leukemia inhibitory factor (LIF), macrophage colony-stimulating factor (M-CSF) and human stem cell growth factor (SCF), to support hematopoiesis (Amini et al, 2018;Mohammadali, Abroun & Atashi, 2018). HBMSCs also regulate immune function and do not show immunological characteristics consistent with rejection (Liu et al, 2018;Gabr et al, 2017;Lee et al, 2017).…”

Section: Discussionmentioning

confidence: 99%

Bioinformatics analysis and identification of circular RNAs promoting the osteogenic differentiation of human bone marrow mesenchymal stem cells on titanium treated by surface mechanical attrition

Zhu

Wang

et al. 2020

PeerJ

View full text Add to dashboard Cite

Background To analyze and identify the circular RNAs (circRNAs) involved in promoting the osteogenic differentiation of human bone mesenchymal stem cells (hBMSCs) on titanium by surface mechanical attrition treatment (SMAT). Methods The experimental material was SMAT titanium and the control material was annealed titanium. Cell Counting Kits-8 (CCK-8) was used to detect the proliferation of hBMSCs, and alkaline phosphatase (ALP) activity and alizarin red staining were used to detect the osteogenic differentiation of hBMSCs on the sample surfaces. The bioinformatics prediction software miwalk3.0 was used to construct competing endogenous RNA (ceRNA) networks by predicting circRNAs with osteogenesis-related messenger RNAs (mRNAs) and microRNAs (miRNAs). The circRNAs located at the key positions in the networks were selected and analyzed by quantitative real-time PCR (QRT-PCR). Results Compared with annealed titanium, SMAT titanium could promote the proliferation and osteogenic differentiation of hBMSCs. The total number of predicted circRNAs was 51. Among these, 30 circRNAs and 8 miRNAs constituted 6 ceRNA networks. Circ-LTBP2 was selected for verification. QRT-PCR results showed that the expression levels of hsa_circ_0032599, hsa_circ_0032600 and hsa_circ_0032601 were upregulated in the experimental group compared with those in the control group; the differential expression of hsa_circ_0032600 was the most obvious and statistically significant, with a fold change (FC) = 4.25 ± 1.60, p-values (p) < 0.05.

show abstract

Combined mild hypoxia and bone marrow mesenchymal stem cells improve expansion and HOXB4 gene expression of human cord blood CD34+ stem cells

Abstract: How to cite this article: Mohammadali F, Abroun S, Atashi A. Combined mild hypoxia and bone marrow mesenchymal stem cells improve expansion and HOXB4 gene expression of human cord blood CD34+ stem cells.

Cited by 10 publications

References 42 publications

The Incorporation of Extracellular Vesicles from Mesenchymal Stromal Cells Into CD34+ Cells Increases Their Clonogenic Capacity and Bone Marrow Lodging Ability

The Incorporation of Extracellular Vesicles from Mesenchymal Stromal Cells Into CD34+ Cells Increases Their Clonogenic Capacity and Bone Marrow Lodging Ability

Antioxidant Small Molecule Compound Chrysin Promotes the Self-Renewal of Hematopoietic Stem Cells

Bioinformatics analysis and identification of circular RNAs promoting the osteogenic differentiation of human bone marrow mesenchymal stem cells on titanium treated by surface mechanical attrition

Contact Info

Product

Resources

About