CD34 positive cells as endothelial progenitor cells in biology and medicine

Hassanpour, Mehdi; Salybekov, Amankeldi A.; Kobayashi, Shuzo; Asahara, Takayuki

doi:10.3389/fcell.2023.1128134

Cited by 33 publications

(9 citation statements)

References 158 publications

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“…EPC homing as well as retaining in the tissue site of infection and inflammation will facilitate local release of angiogenic factors by these vascular precursors to fulfill their paracrine as well as autocrine effects. In addition to producing angiogenic factors, EPCs have been reported to exert immunomodulatory effects via producing anti-inflammatory cytokines, including IL-4 and IL-10 ( 42 ). With secretion of these anti-inflammatory cytokines, EPCs interplay with immune cell types via promoting differentiation of macrophages toward the M2 phenotype and proliferation of T-regulatory cells (Tregs).…”

Section: Discussionmentioning

confidence: 99%

The bone marrow endothelial progenitor cell response to septic infection

Shi,

Simms,

Ewing

et al. 2024

Front. Immunol.

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Early increase in the level of endothelial progenitor cells (EPCs) in the systemic circulation occurs in patients with septic infection/sepsis. The significance and underlying mechanisms of this response remain unclear. This study investigated the bone marrow EPC response in adult mice with septic infection induced by intravenous injection (i.v.) of Escherichia coli. For in vitro experiments, sorted marrow stem/progenitor cells (SPCs) including lineage(lin)-stem cell factor receptor (c-kit)+stem cell antigen-1 (Sca-1)−, lin−c-kit+, and lin− cells were cultured with or without lipopolysaccharides (LPSs) and recombinant murine vascular endothelial growth factor (VEGF) in the absence and presence of anti-Sca-1 crosslinking antibodies. In a separate set of experiments, marrow lin−c-kit+ cells from green fluorescence protein (GFP)+ mice, i.v. challenged with heat-inactivated E. coli or saline for 24 h, were subcutaneously implanted in Matrigel plugs for 5 weeks. Marrow lin−c-kit+ cells from Sca-1 knockout (KO) mice challenged with heat-inactivated E. coli for 24 h were cultured in the Matrigel medium for 8 weeks. The marrow pool of EPCs bearing the lin−c-kit+Sca-1+VEGF receptor 2 (VEGFR2)+ (LKS VEGFR2+) and LKS CD133+VEGFR2+ surface markers expanded rapidly following septic infection, which was supported by both proliferative activation and phenotypic conversion of marrow stem/progenitor cells. Increase in marrow EPCs and their reprogramming for enhancing angiogenic activity correlated with cell-marked upregulation of Sca-1 expression. Sca-1 was coupled with Ras-related C3 botulinum toxin substrate 2 (Rac2) in signaling the marrow EPC response. Septic infection caused a substantial increase in plasma levels of IFN-γ, VEGF, G-CSF, and SDF-1. The early increase in circulating EPCs was accompanied by their active homing and incorporation into pulmonary microvasculature. These results demonstrate that the marrow EPC response is a critical component of the host defense system. Sca-1 signaling plays a pivotal role in the regulation of EPC response in mice with septic infection.

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Section: Discussionmentioning

confidence: 99%

The bone marrow endothelial progenitor cell response to septic infection

Shi,

Simms,

Ewing

et al. 2024

Front. Immunol.

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“…We know that despite the virus causing T-cell cytokine storms in infected patients, some of them survive and some die. Hence, it is highly unlikely that ACE2-negative T-cells can compete with ACE2 + (hemangioblasts, CD133 + CD34 +/− ) ( Sidney et al, 2014 ; Koka et al, 2020 ; Hassanpour et al, 2023 ) cells in receiving or harbouring the virus to such an extent that can cause the death of SARS-CoV-2 infected patients unless as an indirect consequence on the secondary T-cells.…”

Section: Discussionmentioning

confidence: 99%

“…SARS-CoV-2 directly targets the precursors which are the pluripotent hemangioblasts that possess lineage commitment into the dual multipotent lineages of CD34 + hematopoietic stem-progenitor cells (HSPC) and CD133 + endothelial stem-progenitor cells (ESPC) ( Sidney et al, 2014 ; Hassanpour et al, 2023 ). Whether these ESPCs retain the hematopoietic stem-progenitor cells’ (HSPC) surface marker antigen CD34 (CD133 + CD34 + ), or negative for CD34 (CD133 + CD34 − ), these progenitor stem cells co-express the ACE2 cell-surface antigen, the latter being the primary receptor for SARS-CoV-2 entry into the ACE2 + (CD133 + CD34 +/− ) ESPC.…”

Section: Introductionmentioning

confidence: 99%

Contrasting mechanistic susceptibilities of hematopoietic and endothelial stem-progenitor cells in respective pathogeneses of HIV-1 and SARS-CoV-2 infections

Koka,

Ramdass

2023

Front. Cell Dev. Biol.

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The multitude of cellular types can be expected to behave differently when receiving invading pathogens such as mammalian viruses. The nature-dictated causes for such intrinsic cellular diversity become the criteria for the emergence of specific virus-receptor interactions on that particular host cellular surface, in order to accommodate contact with various other living entities whether desirable to the host or not. At present, we are presented with an example of two contrasting behaviours wherein the well-known HIV-1 and the more recently emergent SARS-CoV-2 cause adverse consequences to the differentiation and functions of progenitor stem cells. These include the two different downstream multipotent CD34+ hematopoietic (HSPC) and CD133+ endothelial (ESPC) stem-progenitor cells of their common pluripotent hemangioblast precursors. The two viruses target the respective endothelial and hematopoietic stem-progenitor cells to thrive upon the relevant host cellular surrounded stromal microenvironments by adopting reciprocally-driven mechanistic routes, which incidentally cause pathogenesis either directly of ESPC (SARS-CoV-2), or indirectly of HSPC (HIV-1). HIV-1 utilizes the CD4+ T-lymphocyte receptor thereby advancing pathogenesis indirectly to the CD34+ HSPC. SARS-CoV-2 directly targets the CD133+ ESPC via ACE2 receptor causing cytokine storms of the CD4+ T-lymphocytes. In this manner, these two viruses cause and extend their damage to the other cellular sub/types coexisting in the host cellular microenvironments. The infected individuals require clinical interventions that are efficacious to prevent cellular dysfunction and ultimate cell depletion or death. We infer from these viruses mediated pathogeneses mechanisms a potential common origin of microRNA molecular therapies to address cellular dysfunctions and prevent cell loss.

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“…To further assess the endothelial characteristics of eEPC lines, we initially tested the expression of the key endothelial markers, such as cluster of differentiation (CD) 31, VE-Cadherin (CD144), vascular endothelial growth factor receptor (VEGFR-2)/KDR, and Von Willebrand factor (vWF), which are all widely recognized as endothelial-specific markers [10,29] and CD34, which is known as an EPC marker [30]. Phase contrast imaging of representative eEPC lines displayed a cobblestone shape morphology (Figure 4A), and 98.9% eEPC population expressed CD34+/CD31+ cells according to single cell flow cytometric analysis (Figure 4B).…”

Section: Eepc Lines Express Surface Proteins and Cellular Markers Of ...mentioning

confidence: 99%

Clonal and Scalable Endothelial Progenitor Cell Lines from Human Pluripotent Stem Cells

Lee,

Sternberg,

Bignone

et al. 2023

Biomedicines

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Human pluripotent stem cells (hPSCs) can be used as a renewable source of endothelial cells for treating cardiovascular disease and other ischemic conditions. Here, we present the derivation and characterization of a panel of distinct clonal embryonic endothelial progenitor cells (eEPCs) lines that were differentiated from human embryonic stem cells (hESCs). The hESC line, ESI-017, was first partially differentiated to produce candidate cultures from which eEPCs were cloned. Endothelial cell identity was assessed by transcriptomic analysis, cell surface marker expression, immunocytochemical marker analysis, and functional analysis of cells and exosomes using vascular network forming assays. The transcriptome of the eEPC lines was compared to various adult endothelial lines as well as various non-endothelial cells including both adult and embryonic origins. This resulted in a variety of distinct cell lines with functional properties of endothelial cells and strong transcriptomic similarity to adult endothelial primary cell lines. The eEPC lines, however, were distinguished from adult endothelium by their novel pattern of embryonic gene expression. We demonstrated eEPC line scalability of up to 80 population doublings (pd) and stable long-term expansion of over 50 pd with stable angiogenic properties at late passage. Taken together, these data support the finding that hESC-derived clonal eEPC lines are a potential source of scalable therapeutic cells and cell products for treating cardiovascular disease. These eEPC lines offer a highly promising resource for the development of further preclinical studies aimed at therapeutic interventions.

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CD34 positive cells as endothelial progenitor cells in biology and medicine

Cited by 33 publications

References 158 publications

The bone marrow endothelial progenitor cell response to septic infection

The bone marrow endothelial progenitor cell response to septic infection

Contrasting mechanistic susceptibilities of hematopoietic and endothelial stem-progenitor cells in respective pathogeneses of HIV-1 and SARS-CoV-2 infections

Clonal and Scalable Endothelial Progenitor Cell Lines from Human Pluripotent Stem Cells

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