scholarly journals Shh, BMP4 and IL-7 in the maintenance and differentiation of human CD34+ progenitor cells in the thymus

Cell Cycle ◽  
2009 ◽  
Vol 8 (23) ◽  
pp. 3809-3815
Author(s):  
Anna L. Furmanski ◽  
Tessa Crompton
Keyword(s):  
Progenitor Cells ◽  
Human Cd34

Infection of human CD34+ progenitor cells with Bartonella henselae results in intraerythrocytic presence of B henselae

Blood ◽  
2005 ◽  
Vol 106 (4) ◽  
pp. 1215-1222 ◽  
Author(s):  
Tanja Mändle ◽  
Hermann Einsele ◽  
Martin Schaller ◽  
Diana Neumann ◽  
Wichard Vogel ◽  
...  
Keyword(s):  
Progenitor Cells ◽  
Laser Scanning ◽  
Bartonella Henselae ◽  
Bacterial Pathogen ◽  
Erythroid Differentiation ◽  
Laser Scanning Microscopy ◽  
Confocal Laser ◽  
Facs Analysis ◽  
Human Cd34 ◽  
First Time

Abstract Although there is evidence that endothelial cells are important targets for human pathogenic Bartonella species, the primary niche of infection is unknown. Here we elucidated whether human CD34+ hematopoietic progenitor cells (HPCs) internalize B henselae and may serve as a potential niche of the pathogen. We showed that B henselae does not adhere to or invade human erythrocytes. In contrast, B henselae invades and persists in HPCs as shown by gentamicin protection assays, confocal laser scanning microscopy (CLSM), and electron microscopy (EM). Fluorescence-activated cell sorting (FACS) analysis of glycophorin A expression revealed that erythroid differentiation of HPCs was unaffected following infection with B henselae. The number of intracellular B henselae continuously increased over a 13-day period. When HPCs were infected with B henselae immediately after isolation, intracellular bacteria were subsequently detectable in differentiated erythroid cells on day 9 and day 13 after infection, as shown by CLSM, EM, and FACS analysis. Our data provide, for the first time, evidence that a bacterial pathogen is able to infect and persist in differentiating HPCs, and suggest that HPCs might serve as a potential primary niche in Bartonella infections.

scholarly journals Phenotype and function of human hematopoietic cells engrafting immune- deficient CB17-severe combined immunodeficiency mice and nonobese diabetic-severe combined immunodeficiency mice after transplantation of human cord blood mononuclear cells

Blood ◽  
1996 ◽  
Vol 88 (10) ◽  
pp. 3731-3740 ◽  
Author(s):  
F Pflumio ◽  
B Izac ◽  
A Katz ◽  
LD Shultz ◽  
W Vainchenker ◽  
...  
Keyword(s):  
Cord Blood ◽  
Progenitor Cells ◽  
Mononuclear Cells ◽  
Severe Combined Immunodeficiency ◽  
Human Cells ◽  
Scid Mice ◽  
Combined Immunodeficiency ◽  
Human Cd34 ◽  
Blood Mononuclear Cells ◽  
Cord Blood Mononuclear Cells

In an attempt to understand better the regulation of stem cell function in chimeric immunodeficient mice transplanted with human cells, and the filiation between progenitor cells identified in vitro and in vivo, we assessed the different compartments of hematopoietic progenitors found in the marrow of CB17-severe combined immunodeficiency (SCID) mice (34 mice, 9 experiments) after intravenous injection of 2 to 3 x 10(7) cord blood mononuclear cells. On average 6.3 +/-4 x 10(5) human cells were detected per four long bones 4 to 6 weeks after the transplant predominantly represented by granulomonocytic (CD11b+) and B lymphoid (CD19+) cells. Twenty five percent of these human cells expressed the CD34 antigen, of which 90% coexpressed the CD38 antigen and 50% the CD19 antigen. Functional assessment of progenitor cells (both clonogenic and long-term culture-initiating cells [LTC-IC]) was performed after human CD34+ cells and CD34+/CD38- cells have been sorted from chimeric CB17-SCID marrow 3 to 10 weeks after intravenous (IV) injection of human cells. The frequency of both colony-forming cells and LTC-IC was low (4% and 0.4%, respectively in the CD34+ fraction) when compared with the frequencies of cells with similar function in CD34+ cells from the starting cord blood mononuclear cells (26% +/- 7% and 7.2% +/- 5%, respectively). More surprisingly, the frequency of LTC-IC was also low in the human CD34+ CD38- fraction sorted from chimeric mice. This observation might be partly accounted for by the expansion of the CD34+ CD19+ B-cell precursor compartment. Despite their decreased frequency and absolute numbers, the differentiation capability of these LTC-IC, assessed by their clonogenic progeny output after 5 weeks in coculture with murine stromal cells was intact when compared with that of input LTC-IC. Furthermore the ratio between clonogenic progenitor cells and LTC-IC was similar in severe combined immunodeficiency (SCID) mice studied 4 weeks after transplant and in adult marrow or cord blood suspensions. Results generated in experiments where nonobese diabetic (NOD)-SCID mice were used as recipients indicate a higher level of engraftment but no change in the distribution of clonogenic cells or LTC-IC. These results suggest that the hierarchy of hematopoietic differentiation classically defined in human hematopoietic tissues can be reconstituted in immunodeficient SCID or NOD-SCID mice.

Efficient transient genetic labeling of human CD34+progenitor cells forin vivoapplication

2006 ◽  
Vol 1 (2) ◽  
pp. 223-234 ◽  
Author(s):  
Juliane MI Wiehe ◽  
Carola Niesler ◽  
Jan Torzewski ◽  
Oliver Zimmermann ◽  
Markus Wiesneth ◽  
...  
Keyword(s):  
Progenitor Cells ◽  
Human Cd34 ◽  
Genetic Labeling

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 Development of a retroviral construct containing a human mutated dihydrofolate reductase cDNA for hematopoietic stem cell transduction

Blood ◽  
1994 ◽  
Vol 83 (11) ◽  
pp. 3403-3408 ◽  
Author(s):  
MX Li ◽  
D Banerjee ◽  
SC Zhao ◽  
BI Schweitzer ◽  
S Mineishi ◽  
...  
Keyword(s):  
Progenitor Cells ◽  
Dihydrofolate Reductase ◽  
Leukemia Virus ◽  
Mouse Bone Marrow ◽  
Peripheral Blood Stem Cells ◽  
Hematopoietic Stem ◽  
Proviral Dna ◽  
Human Cd34 ◽  
Blood Stem Cells

Abstract A double-copy Moloney leukemia virus-based retroviral construct containing both the NeoR gene and a mutant human dihydrofolate reductase (DHFR) cDNA (Ser31 mutant) was used to transduce NIH 3T3 and mouse bone marrow (BM) progenitor cells. This resulted in increased resistance of these cells to methotrexate (MTX). The transduced BM progenitor cells were returned to lethally irradiated mice. The recipients transplanted with marrow cells infected with the recombinant virus showed protection from lethal MTX toxicity as compared with mock- infected animals. Evidence for integration of the proviral DNA was obtained by amplification of proviral DNA by polymerase chain reaction (PCR) and Southern analysis. Sequencing a portion of the PCR-amplified human DHFR cDNA showed the presence of the mutation. These studies with the human Ser31 mutant DHFR cDNA gave results comparable with those obtained with the mutant murine DHFR cDNA (Leu to Arg22) in developing MTX-resistant BM. The Ser31 mutant human DHFR cDNA is currently being tested for infection of human CD34+ human BM and peripheral blood stem cells in vitro.

scholarly journals Sustained human hematopoiesis in immunodeficient mice by cotransplantation of marrow stroma expressing human interleukin-3: analysis of gene transduction of long-lived progenitors

Blood ◽  
1994 ◽  
Vol 83 (10) ◽  
pp. 3041-3051 ◽  
Author(s):  
JA Nolta ◽  
MB Hanley ◽  
DB Kohn
Keyword(s):  
Stem Cells ◽  
Progenitor Cells ◽  
Blood Cells ◽  
Gene Transduction ◽  
Hematopoietic Stem ◽  
Immunodeficient Mice ◽  
Interleukin 3 ◽  
Human Cd34 ◽  
Time Period

Abstract We have developed a novel cotransplantation system in which gene- transduced human CD34+ progenitor cells are transplanted into immunodeficient (bnx) mice together with primary human bone marrow (BM) stromal cells engineered to produce human interleukin-3 (IL-3). The IL- 3-secreting stroma produced sustained circulating levels of human IL-3 for at least 4 months in the mice. The IL-3-secreting stroma, but not control stroma, supported human hematopoiesis from the cotransplanted human BM CD34+ progenitors for up to 9 months, such that an average of 6% of the hematopoietic cells removed from the mice were of human origin (human CD45+). Human multilineage progenitors were readily detected as colony-forming units from the mouse marrow over this time period. Retroviral-mediated transfer of the neomycin phosphotransferase gene or a human glucocerebrosidase cDNA into the human CD34+ progenitor cells was performed in vitro before cotransplantation. Human multilineage progenitors were recovered from the marrow of the mice 4 to 9 months later and were shown to contain the transduced genes. Mature human blood cells marked by vector DNA circulated in the murine peripheral blood throughout this time period. This xenograft system will be useful in the study of gene transduction of human hematopoietic stem cells, by tracing the development of individually marked BM stem cells into mature blood cells of different lineages.

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