scholarly journals Platelet-Derived Stromal Cell–Derived Factor-1 Regulates Adhesion and Promotes Differentiation of Human CD34+Cells to Endothelial Progenitor Cells

Circulation ◽  
2008 ◽  
Vol 117 (2) ◽  
pp. 206-215 ◽  
Author(s):  
Konstantinos Stellos ◽  
Harald Langer ◽  
Karin Daub ◽  
Tanja Schoenberger ◽  
Alexandra Gauss ◽  
...  
Keyword(s):  
Progenitor Cells ◽  
Endothelial Progenitor Cells ◽  
Stromal Cell ◽  
Endothelial Progenitor ◽  
Human Cd34 ◽  
Cd34 Cells ◽  
Stromal Cell Derived Factor

Abstract 42: In Vivo Differentiation of Epigenetically Reprogrammed Human Endothelial Progenitor Cells into Cardiomyocytes Enhances Functional and Anatomical Postinfarct Myocardial Repair

2012 ◽  
Vol 111 (suppl_1) ◽  
Author(s):  
Melissa A Thal ◽  
Prasanna Krishnamurthy ◽  
Alexander R Mackie ◽  
Eneda Hoxha ◽  
Erin Lambers ◽  
...  
Keyword(s):  
Heart Disease ◽  
Ischemic Heart Disease ◽  
Progenitor Cells ◽  
Endothelial Progenitor Cells ◽  
Ischemic Heart ◽  
Specific Gene ◽  
Myocardial Repair ◽  
Endothelial Progenitor ◽  
Human Cd34 ◽  
Cd34 Cells

Currently, bone marrow derived endothelial progenitor cells (human CD34+ cells, EPC) are being used clinically to improve vascularization in patients with ischemic heart disease. While it is generally accepted that CD34+ cells predominantly work through a paracrine mechanism, there exists no convincing evidence that these cells trans-differentiate into functional cardiomyocytes (CMC). Since ischemic heart disease leads to substantial loss of CMC, improving cardiomyogenic plasticity of an existing autologous cell therapy is of obvious import. EPC and CMC both differentiate from a common mesodermal progenitor however; during EC-specific lineage differentiation, CMC specific genes are epigenetically silenced. We hypothesized that reprogramming of CD34+ cells using small molecules targeting key epigenetic repressive marks may recapitulate their cardiomyogenic potential. Human CD34+ EPCs were treated with inhibitors of histone deacetylases (valproic acid) for 24 hours followed by an additional 24 hours with the DNA methyltransferase inhibitor (5-Azacytidine). This forty-eight hour treatment led to the reactivation of pluripotency associated and CMC specific mRNA expression while EC specific gene expression was maintained. Intra-myocardial transplantation of a sub-therapeutic dose of reprogrammed CD34+ cells in an acute myocardial infarction mouse model showed significant improvement in LV function compared to the same number of control CD34+ cells that are therapeutically equivalent to no treatment at all. This was histologically supported by de novo CMC differentiation. In addition to increased cardiomyogenic plasticity, drug treatment also enhanced the inherent therapeutic capacity of the CD34+ cells as shown by reduced fibrosis, increased capillary density, increased proliferation, increased cell survival and increased secretion of angiogenic factors. Taken together, our results suggest that epigenetically reprogrammed CD34+ cells are “super-CD34+ cells” that have an enhanced paracrine effect, display a more plastic phenotype and improve post-infarct cardiac repair by both neo-cardiomyogenesis and neovascularization.

scholarly journals Exercise Induces Stromal Cell–Derived Factor-1α–Mediated Release of Endothelial Progenitor Cells with Increased Vasculogenic Function

2015 ◽  
Vol 135 (2) ◽  
pp. 340e-350e ◽  
Author(s):  
Edwin Chang ◽  
Josemaria Paterno ◽  
Dominik Duscher ◽  
Zeshaan N. Maan ◽  
Jerry S. Chen ◽  
...  
Keyword(s):  
Progenitor Cells ◽  
Endothelial Progenitor Cells ◽  
Stromal Cell ◽  
Endothelial Progenitor ◽  
Stromal Cell Derived Factor

scholarly journals Active Stromal Cell–Derived Factor 1α and Endothelial Progenitor Cells are Equally Increased by Alogliptin in Good and Poor Diabetes Control

2017 ◽  
Vol 10 ◽  
pp. 117955141774398 ◽  
Author(s):  
Roberto Negro ◽  
Eupremio Luigi Greco ◽  
Giacomo Greco
Keyword(s):  
Progenitor Cells ◽  
Endothelial Progenitor Cells ◽  
Stromal Cell ◽  
Diabetes Control ◽  
Diabetic Patients ◽  
Endothelial Progenitor ◽  
Dipeptidyl Peptidase 4 Inhibitors ◽  
Group A ◽  
Stromal Cell Derived Factor ◽  
Group B

Background: It is postulated that the ability of dipeptidyl peptidase-4 inhibitors (DPP-4-i) to increase circulating endothelial progenitor cells (EPCs) may be at least partly mediated by active stromal cell–derived factor 1α (SDF-1α) (a pivotal mediator of stem cell mobilization from the bone marrow). As other DPP-4-i were demonstrated to increase EPC concentrations, in this study, we sought to investigate the ability of the DPP-4-i alogliptin in modifying EPCs and SDF-1α, in patients with good and poor diabetes control. Methods: Two groups of diabetic patients on metformin were divided by hemoglobin A1c (HbA1c): Group A—those with HbA1c ≤6.5% (28 patients) and Group B—those with HbA1c 7.5% to 8.5% (31 patients). Both groups received alogliptin 25 mg/daily for 4 months. At baseline and 4 months later, clinical, laboratory parameters, EPCs, and active SDF-1α were determined. Results: After 4-month treatment with alogliptin, either Group A or Group B showed reduced HbA1c levels and concomitant similar increase in EPCs and active SDF-1α. Conclusions: Alogliptin showed significant benefits in increasing EPCs and active SDF-1α either in good or poor diabetes control. The study demonstrated that similar to other DPP-4-i, also alogliptin is able to increase EPC concentrations, suggesting the existence of a class effect mediated by SDF-1α. The extent of increase in EPCs is independent from baseline diabetes control.

Human CD34+ Cells Express CXCR4 and Its Ligand Stromal Cell–Derived Factor-1. Implications for Infection by T-Cell Tropic Human Immunodeficiency Virus

Blood ◽  
1999 ◽  
Vol 94 (1) ◽  
pp. 62-73 ◽  
Author(s):  
Alessandro Aiuti ◽  
Lucia Turchetto ◽  
Manuela Cota ◽  
Arcadi Cipponi ◽  
Andrea Brambilla ◽  
...  
Keyword(s):  
Human Immunodeficiency Virus ◽  
T Cell ◽  
Progenitor Cells ◽  
Stromal Cell ◽  
Human Cd34 ◽  
Cd34 Cells ◽  
Immunodeficiency Virus ◽  
Stromal Cell Derived Factor ◽  
Hiv 1

Human CD34+ hematopoietic progenitor cells obtained from bone marrow (BM), umbilical cord blood (UCB), and mobilized peripheral blood (MPB) were purified and investigated for the expression of the chemokine receptor CXCR4 and its ligand, stromal cell–derived factor-1 (SDF-1). CXCR4 was found present on the cell surface of all CD34+ cells, although it was expressed at lower density on MPB with respect to BM CD34+ cells. Freshly isolated and in vitro–cultured CD34+ cells also coexpressed SDF-1 mRNA, as determined by reverse transcriptase-polymerase chain reaction (RT-PCR). Of interest, CD34+/CD38+ committed progenitor cells, unlike primitive CD34+/CD38− cells, expressed SDF-1 mRNA. Supernatants from in vitro–cultured CD34+ cells contained substantial (3 to 8 ng/mL) amounts of SDF-1 by enzyme-linked immunosorbent assay and induced migration of CD34+ cells. Because CD34+ cells express low levels of CD4, the primary receptor of the human immunodeficiency virus (HIV), and CXCR4 is a coreceptor for T-cell tropic (X4) HIV strains, we investigated the susceptibility of CD34+cells to infection by this subset of viruses. Lack of productive infection was almost invariably observed as determined by a conventional RT activity in culture supernatants and by real-time PCR for HIV DNA in CD34+ cells exposed to both laboratory adapted (LAI) and primary (BON) X4 T-cell tropic HIV-1 strain. Soluble gp120 Env (sgp120) from X4 HIV-1 efficiently blocked binding of the anti-CD4 Leu3a monoclonal antibody (MoAb) to either human CD4+ T cells or CD34+ cells. In contrast, sgp120 interfered with an anti-CXCR4 MoAb binding to human T lymphocytes, but not to CD34+ cells. However, CXCR4 on CD34+ cells was downregulated by SDF-1. These results suggest that CXCR4 and its ligand SDF-1 expressed in CD34+ progenitors may play an important role in regulating the local and systemic trafficking of these cells. Moreover, these findings suggest multiple and potentially synergistic mechanisms at the basis of the resistance of CD34+ cells to X4 HIV infection, including their ability to produce SDF-1, and the lack of CXCR4 internalization following gp120 binding to CD4.

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