Human CD34+ very small embryonic-like stem cells can give rise to endothelial colony-forming cells with a multistep differentiation strategy using UM171 and nicotinamide acid

Domingues, Alison; Rossi, Elisa; Bujko, Kamila; Détriché, Grégoire; Richez, Ulysse; Blandinières, Adeline; Kucia, Magdalena; Ratajczak, Janina; Smadja, David M.; Ratajczak, Mariusz Z.

doi:10.1038/s41375-022-01517-0

Cited by 16 publications

(15 citation statements)

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“…The inability of VSELs to achieve this state is basically because of their unique epigenetic status and their quiescent state due to the erasure of differently methylated regions (DMRs) at some of the paternally imprinted genes involved in embryogenesis (Shin et al, 2010;Ratajczak et al, 2019), which allow them to achieve what the hES/iPS cells cannot (Figure 1A). Recent attempts to expand VSELs in vitro by treating with epigenetic modulators, such as pyrimidoindole derivative (UM171) and nicotinamide acid, were successful (Lahlil et al, 2018;Domingues et al, 2022). CD34 + cells are now being produced on an industrial scale in a "good manufacturing practice" facility with an increased fraction of LIN -CD45 -CD133 + VSELs (Henon et al, 2022).…”

Section: An Introduction To Vselsmentioning

confidence: 99%

“…CD34 + cells are now being produced on an industrial scale in a “good manufacturing practice” facility with an increased fraction of LIN – CD45 – CD133 + VSELs ( Henon et al, 2022 ). Meanwhile, Domingues et al (2022) showed that CD34 + VSELs represent an excellent source of true vasculogenic endothelial progenitors for vascular repair, especially since both ES and iPS cells have failed to show similar potential. Ratajczak et al (2011) differentiated VSELs into HSCs in vitro by culturing on OP9 feeder support.…”

Section: Introductionmentioning

confidence: 99%

“… Ratajczak et al (2011) differentiated VSELs into HSCs in vitro by culturing on OP9 feeder support. VSELs sit at the top of the hematopoietic system hierarchy and give rise to HSCs, MSCs, and EPCs ( Figure 1B ), which further differentiate into all types of blood cells, pericytes, and endothelial cells ( Taichman et al, 2010 ; Domingues et al, 2022 ).…”

Section: Introductionmentioning

confidence: 99%

“…VSELs are at the top of the hierarchy that comprises HSCs, MSCs, and EPCs. VSELs are more primitive and give rise to progenitor HSCs ( Taichman et al, 2010 ; Ratajczak et al, 2011a ; Domingues et al, 2022 ) by undergoing asymmetrical cell divisions ( Ganguly et al, 2018 ). VSELs are 2–6 µm cells with a surface phenotype of LIN – CD45 – CD133 + in humans and LIN – CD45 – SCA-1 + in mice, whereas HSCs have a surface phenotype of LIN – CD45 + CD133 + in humans and LIN – CD45 + SCA-1 + in mice.…”

Section: Introductionmentioning

confidence: 99%

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Very small embryonic-like stem cells have the potential to win the three-front war on tissue damage, cancer, and aging

Bhartiya¹,

Jha²,

Tripathi³

et al. 2023

Front. Cell Dev. Biol.

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The concept of dedifferentiation and reprogramming of mature somatic cells holds much promise for the three-front “war” against tissue damage, cancer, and aging. It was hoped that reprogramming human somatic cells into the induced pluripotent state, along with the use of embryonic stem cells, would transform regenerative medicine. However, despite global efforts, clinical applications remain a distant dream, due to associated factors such as genomic instability, tumorigenicity, immunogenicity, and heterogeneity. Meanwhile, the expression of embryonic (pluripotent) markers in multiple cancers has baffled the scientific community, and it has been suggested that somatic cells dedifferentiate and “reprogram” into the pluripotent state in vivo to initiate cancer. It has also been suggested that aging can be reversed by partial reprogramming in vivo. However, better methods are needed; using vectors or Yamanaka factors in vivo, for example, is dangerous, and many potential anti-aging therapies carry the same risks as those using induced pluripotent cells, as described above. The present perspective examines the potential of endogenous, pluripotent very small embryonic-like stem cells (VSELs). These cells are naturally present in multiple tissues; they routinely replace diseased tissue and ensure regeneration to maintain life-long homeostasis, and they have the ability to differentiate into adult counterparts. Recent evidence suggests that cancers initiate due to the selective expansion of epigenetically altered VSELs and their blocked differentiation. Furthermore, VSEL numbers have been directly linked to lifespan in studies of long- and short-lived transgenic mice, and VSEL dysfunction has been found in the ovaries of aged mice. To conclude, a greater interest in VSELs, with their potential to address all three fronts of this war, could be the “light at the end of the tunnel.”

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Section: An Introduction To Vselsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Very small embryonic-like stem cells have the potential to win the three-front war on tissue damage, cancer, and aging

Bhartiya¹,

Jha²,

Tripathi³

et al. 2023

Front. Cell Dev. Biol.

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“…Although the proof of BM-derived ECFCs is not approved by the former reports, there are several publication demonstrating that a pluripotent stem cell known as “very small embryonic-like stem cell” (VSEL) is a lineage-negative, CD34 + , CD133 + and CD45 − cell with very small size (<6 µm length) located in BM, and differentiate into ECFC-like ECs in human ( Havens et al, 2014 ; Guerin et al, 2015 ; Lahlil et al, 2018 ; Domingues et al, 2022 ). Also other reports disclosed VSELs derived from cord blood CD34 + cell differentiated into ECFCs ex vivo ( Lahlil et al, 2018 ) ( Domingues et al, 2022 ). We need further insights and discussions regarding the origin of ECFCs.…”

Section: Cd34 + Cell As a Progenitor For Ecsmentioning

confidence: 99%

CD34 positive cells as endothelial progenitor cells in biology and medicine

Hassanpour

Salybekov

Kobayashi

et al. 2023

Front. Cell Dev. Biol.

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CD34 is a cell surface antigen expressed in numerous stem/progenitor cells including hematopoietic stem cells (HSCs) and endothelial progenitor cells (EPCs), which are known to be rich sources of EPCs. Therefore, regenerative therapy using CD34+ cells has attracted interest for application in patients with various vascular, ischemic, and inflammatory diseases. CD34+ cells have recently been reported to improve therapeutic angiogenesis in a variety of diseases. Mechanistically, CD34+ cells are involved in both direct incorporation into the expanding vasculature and paracrine activity through angiogenesis, anti-inflammatory, immunomodulatory, and anti-apoptosis/fibrosis roles, which support the developing microvasculature. Preclinical, pilot, and clinical trials have well documented a track record of safety, practicality, and validity of CD34+ cell therapy in various diseases. However, the clinical application of CD34+ cell therapy has triggered scientific debates and controversies in last decade. This review covers all preexisting scientific literature and prepares an overview of the comprehensive biology of CD34+ cells as well as the preclinical/clinical details of CD34+ cell therapy for regenerative medicine.

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Molecular analysis and comparison of CD34⁺ and CD133⁺ very small embryonic‐like stem cells purified from umbilical cord blood

et al. 2023

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Very small embryonic like stem cells (VSELs) are a dormant population of stem cells that, as proposed, are deposited during embryogenesis in various tissues, including bone marrow (BM). These cells are released under steady state conditions from their tissue locations and circulate at a low level in peripheral blood (PB). Their number increases in response to stressors as well as tissue/organ damage. This increase is evident during neonatal delivery, as delivery stress prompts enrichment of umbilical cord blood (UCB) with VSELs. These cells could be purified from BM, PB, and UCB by multiparameter sorting as a population of very small CXCR4+Lin−CD45− cells that express the CD34 or CD133 antigen. In this report, we evaluated a number of CD34+Lin−CD45− and CD133+Lin−CD45− UCB‐derived VSELs. We also performed initial molecular characterization of both cell populations for expression of selected pluripotency markers and compared these cells at the proteomic level. We noticed that CD133+Lin−CD45− population is more rare and express, at a higher level, mRNA for pluripotency markers Oct‐4 and Nanog as well as the stromal‐derived factor‐1 (SDF‐1) CXCR4 receptor that regulates trafficking of these cells, however both cells population did not significantly differ in the expression of proteins assigned to main biological processes.

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Human CD34+ very small embryonic-like stem cells can give rise to endothelial colony-forming cells with a multistep differentiation strategy using UM171 and nicotinamide acid

Cited by 16 publications

References 15 publications

Very small embryonic-like stem cells have the potential to win the three-front war on tissue damage, cancer, and aging

Very small embryonic-like stem cells have the potential to win the three-front war on tissue damage, cancer, and aging

CD34 positive cells as endothelial progenitor cells in biology and medicine

Molecular analysis and comparison of CD34⁺ and CD133⁺ very small embryonic‐like stem cells purified from umbilical cord blood

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Human CD34+ very small embryonic-like stem cells can give rise to endothelial colony-forming cells with a multistep differentiation strategy using UM171 and nicotinamide acid

Cited by 16 publications

References 15 publications

Very small embryonic-like stem cells have the potential to win the three-front war on tissue damage, cancer, and aging

Very small embryonic-like stem cells have the potential to win the three-front war on tissue damage, cancer, and aging

CD34 positive cells as endothelial progenitor cells in biology and medicine

Molecular analysis and comparison of CD34+ and CD133+ very small embryonic‐like stem cells purified from umbilical cord blood

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Molecular analysis and comparison of CD34⁺ and CD133⁺ very small embryonic‐like stem cells purified from umbilical cord blood