Characterization and Isolation of Very Small Embryonic-like (VSEL) Stem Cells Obtained from Various Human Hematopoietic Cell Sources

Kuruca, Serap Erdem; Çelik, Dolay Damla; Özerkan, Dilşad; Erdemir, Gökçe

doi:10.1007/s12015-019-09896-1

Cited by 16 publications

(16 citation statements)

References 35 publications

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“…To address this important question, we became interested in the potential effect of SARS-CoV-2 on the population of CD45 − cells, known as very small embryonic-like stem cells (VSELs), residing in postnatal tissues. These cells, which have been described and confirmed by several independent laboratories [24][25][26][27][28][29][30][31][32][33][34][35], may become specified into HSCs and EPCs and thus may revive the old concept of the presence of postnatal hemangioblasts in bone marrow [36][37][38][39][40]. Interestingly, several previous reports have indicated that hemangioblasts may be regulated by RAAS mediators [41].…”

Section: Introductionmentioning

confidence: 78%

SARS-CoV-2 Entry Receptor ACE2 Is Expressed on Very Small CD45− Precursors of Hematopoietic and Endothelial Cells and in Response to Virus Spike Protein Activates the Nlrp3 Inflammasome

Ratajczak

Bujko

Ciechanowicz

et al. 2020

Stem Cell Rev and Rep

148

144

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Angiotensin-converting enzyme 2 (ACE2) plays an important role as a member of the renin-angiotensin-aldosterone system (RAAS) in regulating the conversion of angiotensin II (Ang II) into angiotensin (1-7) (Ang [1-7]). But at the same time, while expressed on the surface of human cells, ACE2 is the entry receptor for SARS-CoV-2. Expression of this receptor has been described in several types of cells, including hematopoietic stem cells (HSCs) and endothelial progenitor cells (EPCs), which raises a concern that the virus may infect and damage the stem cell compartment. We demonstrate for the first time that ACE2 and the entry-facilitating transmembrane protease TMPRSS2 are expressed on very small CD133 + CD34 + Lin − CD45 − cells in human umbilical cord blood (UCB), which can be specified into functional HSCs and EPCs. The existence of these cells known as very small embryonic-like stem cells (VSELs) has been confirmed by several laboratories, and some of them may correspond to putative postnatal hemangioblasts. Moreover, we demonstrate for the first time that, in human VSELs and HSCs, the interaction of the ACE2 receptor with the SARS-CoV-2 spike protein activates the Nlrp3 inflammasome, which if hyperactivated may lead to cell death by pyroptosis. Based on this finding, there is a possibility that human VSELs residing in adult tissues could be damaged by SARS-CoV-2, with remote effects on tissue/organ regeneration. We also report that ACE2 is expressed on the surface of murine bone marrow-derived VSELs and HSCs, although it is known that murine cells are not infected by SARS-CoV-2. Finally, human and murine VSELs express several RAAS genes, which sheds new light on the role of these genes in the specification of early-development stem cells.

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Section: Introductionmentioning

confidence: 78%

SARS-CoV-2 Entry Receptor ACE2 Is Expressed on Very Small CD45− Precursors of Hematopoietic and Endothelial Cells and in Response to Virus Spike Protein Activates the Nlrp3 Inflammasome

Ratajczak

Bujko

Ciechanowicz

et al. 2020

Stem Cell Rev and Rep

148

144

View full text Add to dashboard Cite

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“…These cells express markers CD133 and CD34, which are known as pluripotent markers, and to a lesser extent CD90; the cocktail has a similar number of circulating endothelial cells to that reported in response to endothelial damage and dysfunction in many diseases [27]. The CD45cell fraction is similar in size and phenotype to that described for VSELs, but further studies are needed for better cell characterization [28]. Given that PB-NHESC-C is a product obtained from COVID-19 patients, the variability in the cellular number and phenotype is influenced by the immune response to viral infection and the mobilization of progenitor cells to damaged tissue.…”

Section: Discussionmentioning

confidence: 79%

Safety and Efficacy of Autologous Non-Hematopoietic Enriched Stem Cell Nebulization in Covid-19 Patients. A Randomized Clinical Trial, Abu Dhabi 2020.

Carmenate

Alkaabi

Castillo-Aleman

et al. 2021

Preprint

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Background: The novel SARS-Cov-2 has caused the COVID-19 pandemic. Currently, with insufficient worldwide vaccination rates, the identification of treatment solutions to reduce the impact of the virus is urgently needed. Method: An adaptive, multicentric, open-label, and randomized controlled phase I/II clinical trial entitled the “SENTAD-COVID Study” was conducted by the Abu Dhabi Stem Cells Center under conditional exceptional approval by the Emirates Institutional Review Board (IRB) for COVID-19 Research Committee from April 4 to July 31, 2020, using an autologous peripheral blood nonhematopoietic enriched stem cell cocktail (PB-NHESC-C) administered by compressor (jet) nebulization as a complement to standard care therapy. The primary endpoints include safety and efficacy assessments, adverse events, the mortality rate within 28 days, and the time to clinical improvement as measured by a 2-point reduction on a seven-category ordinal scale or discharge from the hospital, whichever occurred first. Results: The study included a total of 139 randomized COVID-19 patients with 69 in the experimental group and 70 in the control group (standard care). Overall survival was 94.20% for the cocktail-treated group vs. 90.27% for the control group. Adverse events occurred in 43 (62.32%) patients receiving PB-NHESC-C vs. 44 (62.86%) in the control group, and most adverse events were related to the disease. After the first nine days of the intervention, 67.3% of cocktail-treated patients recovered and were released from hospitals compared to 53.1% (RR=0.84; 95% CI, 0.56-1.28) in the control group. Improvement, i.e., at least a 2-point reduction in the severity scale, was more frequently observed in cocktail-treated patients (42.0%) than in controls (17.0%) (RR=0.69; 95% CI, 0.56-0.88). Conclusions: Cocktail treatment improved clinical outcomes without increasing adverse events. Thus, the nebulization of PB-NHESC-C was safe and effective for treatment in most of these patients. Trial registration: ClinicalTrials.gov. NCT04473170. Registered 16 July 2020. Retrospectively registered. https://clinicaltrials.gov/ct2/show/NCT04473170.

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“…Kök hücre çalışmaları, son yıllarda biyolojinin temel sorunlarını incelemek ve hastalıkların tedavisinde yeni seçenekler sunmak üzere en çok araştırmanın yapıldığı bir alandır (4). Kök hücre nakli, lösemi ve lenfoma gibi bazı malign kan hastalıkları, kemik iliği yetmezlikleri ile doğumsal kan hastalıklarının tedavisinde sıklıkla başvurulan hayat kurtarıcı yöntemlerden biridir (7). Bu hastalıklara ek olarak diyabette (8); deri kaybı, otoimmün, nörolojik, eklem ve kas hastalıklarında, kardiyovasküler hastalıklarda (9), bazı kanser türlerinde de (10) geniş uygulama alanı bulmaktadır.…”

Section: Hematopoeti̇k Kök Hücreleri̇n Kli̇ni̇k Uygula-madaki̇ Yeri̇unclassified

Hematopoeti̇k Kök Hücre İzolasyonunda Güncel Yöntemler

Okşak¹,

Erdem‐Kuruca²

2021

jmed

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Hematopoietic stem cells are the rare cells in various hematopoietic organs which are found in small numbers (1-100/ml). When these cells are transferred to patients suffering from diabetes, cancer, heart diseases, muscle and joint problems, they will help the patients' bodies with the regeneration of impaired tissues. While the most important problem in the transplantation of autologous stem cells is malignant cell contamination in cancer patients, in allogeneic transplantation, it is immune reactions and tissue rejections. Therefore, clearing of the transplant material from tumour cells and immune cells may support the long-term healthy regeneration of the tissue to which they are transplanted. Although various techniques have been developed for the purification of these cells in terms of clinical use over many years, there is still no sufficiently effective method. In recent years, researchers have shown an increased interest in microfluidic systems because they are easy to use, cheap and highly efficient. In these types of systems designed with various microcapillaries, micropillars and micropores; purification is carried out according to the properties of cells such as size, deformability, cell adhesion and electrical charges. This review aims to explain traditional and emerging hematopoietic stem cell isolation methods and their advantages and disadvantages.

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Characterization and Isolation of Very Small Embryonic-like (VSEL) Stem Cells Obtained from Various Human Hematopoietic Cell Sources

Cited by 16 publications

References 35 publications

SARS-CoV-2 Entry Receptor ACE2 Is Expressed on Very Small CD45− Precursors of Hematopoietic and Endothelial Cells and in Response to Virus Spike Protein Activates the Nlrp3 Inflammasome

SARS-CoV-2 Entry Receptor ACE2 Is Expressed on Very Small CD45− Precursors of Hematopoietic and Endothelial Cells and in Response to Virus Spike Protein Activates the Nlrp3 Inflammasome

Safety and Efficacy of Autologous Non-Hematopoietic Enriched Stem Cell Nebulization in Covid-19 Patients. A Randomized Clinical Trial, Abu Dhabi 2020.

Hematopoeti̇k Kök Hücre İzolasyonunda Güncel Yöntemler

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