scholarly journals Characterization of Cardiac-Resident Progenitor Cells Expressing High Aldehyde Dehydrogenase Activity

2013 ◽  
Vol 2013 ◽  
pp. 1-15 ◽  
Author(s):  
Marc-Estienne Roehrich ◽  
Albert Spicher ◽  
Giuseppina Milano ◽  
Giuseppe Vassalli
Keyword(s):  
Progenitor Cells ◽  
Aldehyde Dehydrogenase ◽  
Preclinical Studies ◽  
Cell Passage ◽  
Aldh Activity ◽  
Human Cord Blood ◽  
Angiogenic Activity ◽  
Stem And Progenitor Cells ◽  
Aldehyde Dehydrogenase Activity

High aldehyde dehydrogenase (ALDH) activity has been associated with stem and progenitor cells in various tissues. Human cord blood and bone marrow ALDH-bright (ALDHbr) cells have displayed angiogenic activity in preclinical studies and have been shown to be safe in clinical trials in patients with ischemic cardiovascular disease. The presence of ALDHbrcells in the heart has not been evaluated so far. We have characterized ALDHbrcells isolated from mouse hearts. One percent of nonmyocytic cells from neonatal and adult hearts were ALDHbr. ALDHvery-brcells were more frequent in neonatal hearts than adult. ALDHbrcells were more frequent in atria than ventricles. Expression of ALDH1A1 isozyme transcripts was highest in ALDHvery-brcells, intermediate in ALDHbrcells, and lowest in ALDHdimcells. ALDH1A2 expression was highest in ALDHvery-brcells, intermediate in ALDHdimcells, and lowest in ALDHbrcells. ALDH1A3 and ALDH2 expression was detectable in ALDHvery-brand ALDHbrcells, unlike ALDHdimcells, albeit at lower levels compared with ALDH1A1 and ALDH1A2. Freshly isolated ALDHbrcells were enriched for cells expressing stem cell antigen-1, CD34, CD90, CD44, and CD106. ALDHbrcells, unlike ALDHdimcells, could be grown in culture for more than 40 passages. They expressed sarcomericα-actinin and could be differentiated along multiple mesenchymal lineages. However, the proportion of ALDHbrcells declined with cell passage. In conclusion, the cardiac-derived ALDHbrpopulation is enriched for progenitor cells that exhibit mesenchymal progenitor-like characteristics and can be expanded in culture. The regenerative potential of cardiac-derived ALDHbrcells remains to be evaluated.

scholarly journals Antifibrotic effect of lung-resident progenitor cells with high aldehyde dehydrogenase activity

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Hiroshi Takahashi ◽  
Taku Nakashima ◽  
Takeshi Masuda ◽  
Masashi Namba ◽  
Shinjiro Sakamoto ◽  
...  
Keyword(s):  
Pulmonary Fibrosis ◽  
Cell Therapy ◽  
Progenitor Cells ◽  
Aldehyde Dehydrogenase ◽  
Cell Populations ◽  
Aldh Activity ◽  
Aged Mice ◽  
Effects Of Aging ◽  
Aldehyde Dehydrogenase Activity

Abstract Background Aldehyde dehydrogenase (ALDH) is highly expressed in stem/progenitor cells in various tissues, and cell populations with high ALDH activity (ALDHbr) are associated with tissue repair. However, little is known about lung-resident ALDHbr. This study was performed to clarify the characteristics of lung-resident ALDHbr cells and to evaluate their possible use as a tool for cell therapy using a mouse model of bleomycin-induced pulmonary fibrosis. Methods The characteristics of lung-resident/nonhematopoietic (CD45−) ALDHbr cells were assessed in control C57BL/6 mice. The kinetics and the potential usage of CD45−/ALDHbr for cell therapy were investigated in bleomycin-induced pulmonary fibrosis. Localization of transferred CD45−/ALDHbr cells was determined using mCherry-expressing mice as donors. The effects of aging on ALDH expression were also assessed using aged mice. Results Lung CD45−/ALDHbr showed higher proliferative and colony-forming potential than cell populations with low ALDH activity. The CD45−/ALDHbr cell population, and especially its CD45−/ALDHbr/PDGFRα+ subpopulation, was significantly reduced in the lung during bleomycin-induced pulmonary fibrosis. Furthermore, mRNA expression of ALDH isoforms was significantly reduced in the fibrotic lung. When transferred in vivo into bleomycin-pretreated mice, CD45−/ALDHbr cells reached the site of injury, ameliorated pulmonary fibrosis, recovered the reduced expression of ALDH mRNA, and prolonged survival, which was associated with the upregulation of the retinol-metabolizing pathway and the suppression of profibrotic cytokines. The reduction in CD45−/ALDHbr/PDGFRα+ population was more remarkable in aged mice than in young mice. Conclusions Our results strongly suggest that the lung expression of ALDH and lung-resident CD45−/ALDHbr cells are involved in pulmonary fibrosis. The current study signified the possibility that CD45−/ALDHbr cells could find application as novel and useful cell therapy tools in pulmonary fibrosis treatment.

Characterization of hematopoietic stem and progenitor cells

1987 ◽  
Vol 6 (4) ◽  
pp. 294-304 ◽  
Author(s):  
Douglas E. Williams ◽  
Li Lu ◽  
Hal E. Broxmeyer
Keyword(s):  
Progenitor Cells ◽  
Hematopoietic Stem ◽  
Stem And Progenitor Cells

Abstract 860: Phenotypic Characterization Of Murine And Human Cardiac-resident Progenitor Cells Isolated On Basis Of Aldehyde-dehydrogenase Activity

Circulation ◽  
2007 ◽  
Vol 116 (suppl_16) ◽  
Author(s):  
Albert Spicher ◽  
Andrea Meinhardt ◽  
Marc-Estienne Roehrich ◽  
Giuseppe Vassalli
Keyword(s):  
Stem Cells ◽  
Stem Cell ◽  
Progenitor Cells ◽  
Aldehyde Dehydrogenase ◽  
Adult Mouse ◽  
Heart Cells ◽  
Stem Cell Markers ◽  
Aldh Activity ◽  
Differentiation Potential ◽  
Cellular Property

Identification of stem cells based on hematopoietic stem cell (HSC) surface markers, such as stem cell antigen-1 (Sca-1) and the c-kit receptor, has limited specificity. High aldehyde-dehydrogenase (ALDH) activity is a general cellular property of stem cells shared by HSC, neural, and intestinal stem cells. The presence of cells with high ALDH activity in the adult heart has not been investigated. Methods: Cells were isolated from adult mouse hearts, and from atrial appendage samples from humans with ischemic or valvular heart disease. Myocyte-depleted mouse Sca-1+, and lineage (Lin)-negative/c-kit+ human heart cells were purified with immunomagnetic beads. ALDH-high cells were identified using a specific fluorescent substrate, and sorted by FACS. Cell surface marker analysis was performed by flow cytometry. Results: Myocyte-depleted mouse heart cells contained 4.8+/−3.2% ALDH-high/SSC-low and 32.6+/−1.6% Sca-1+ cells. ALDH-high cells were Lin-negative, Sca-1+ CD34+ CD105+ CD106+, contained small CD44+ (27%) and CD45+ (15%) subpopulations, and were essentially negative for c-kit (2%), CD29, CD31, CD133 and Flk-1. After several passages in culture, ~20% of ALDH-high cells remained ALDH-high. Myocyte-depleted human atrial cells contained variable numbers of ALDH-high cells ranging from 0.5% to 11%, and 4% Lin-negative/c-kit+ cells. ALDH-high cells were CD29+ CD105+, contained a small c-kit+ subpopulation (5%), and were negative for CD31, CD45 and CD133. After 5 passages in culture, the majority of ALDH-high cells remained ALDH-high. Conclusions: Adult mouse and human hearts contain significant numbers of cells with high ALDH activity, a general cellular property that stem cells possess in different organs, and express stem cell markers (Sca-1 and CD34 in the mouse). The immunophenotype of cardiac-resident ALDH-high cells differs from that previously described for bone marrow ALDH-high HSC, and suggests that this cell population may be enriched in mesenchymal progenitors. Analysis of lineage differentiation potential of ALDH-high cells is in progress. ALDH activity provides a new, practical approach to purifying cardiac-resident progenitor cells.

scholarly journals Characterization of transcriptional networks in blood stem and progenitor cells using high-throughput single-cell gene expression analysis

2013 ◽  
Vol 15 (4) ◽  
pp. 363-372 ◽  
Author(s):  
Victoria Moignard ◽  
Iain C. Macaulay ◽  
Gemma Swiers ◽  
Florian Buettner ◽  
Judith Schütte ◽  
...  
Keyword(s):  
Gene Expression ◽  
Single Cell ◽  
Progenitor Cells ◽  
High Throughput ◽  
Gene Expression Analysis ◽  
Transcriptional Networks ◽  
Stem And Progenitor Cells ◽  
Cell Gene Expression ◽  
Cell Gene

CD133-Expressing Cells with High Aldehyde Dehydrogenase Activity Represent a Primitive Human Hematopoietic Stem Cell Population with Enhanced Repopulating Potential.

Blood ◽  
2004 ◽  
Vol 104 (11) ◽  
pp. 250-250
Author(s):  
David A. Hess ◽  
Louisa Wirthlin ◽  
Timothy P. Craft ◽  
Todd E. Meyerrose ◽  
Jan A. Nolta
Keyword(s):  
Progenitor Cells ◽  
Aldehyde Dehydrogenase ◽  
Mononuclear Cells ◽  
Phenotypic Expression ◽  
Stem Cell Population ◽  
Human Umbilical Cord Blood ◽  
Human Umbilical Cord ◽  
Aldh Activity ◽  
Hematopoietic Stem ◽  
Selection Of

Abstract Human hematopoietic stem cells (HSC) are commonly purified by the phenotypic expression of cell surface markers such as CD34. We have recently characterized a novel strategy to purify reconstituting HSC from human umbilical cord blood (UCB) by lineage depletion (Lin−) followed by selection of cells with high aldehyde dehydrogenase (ALDH) enzyme activity. Lin− cells with high ALDH activity (ALDHhiLin−) represented approximately 0.1% of total UCB mononuclear cells and demonstrated enriched expression of the primitive HSC markers CD34 (91.0±2.9%) and CD133 (70.9±4.0%). Most notably, clonogenic progenitor function and in vivo reconstituting ability in immune deficient mice were exclusive to the ALDHhiLin− population. Here, we have further purified the ALDHhiLin− population based on the expression of CD133, or prominen, a non-restricted surface molecule expressed on primitive progenitor cells of hematopoietic, endothelial, and neural epithelial lineages. ALDHhiCD133− and ALDHhiCD133+ cells, sorted to >95% purity, represented 14.7±2.1% and 23.2±4.3% of the total human UCB Lin− population respectively (n=6). Both ALDHhiCD133−Lin− and ALDHhiCD133+Lin− cells demonstrated clonogenic progenitor function in vitro. However, total colony production was significantly enhanced (p<0.05) in ALDHhiCD133−Lin− cells (1 CFU in 3.5 cells, n=5) when directly compared to ALDHhiCD133+Lin− cells (1 CFU in 10 cells, n=6). Human hematopoietic repopulation was consistently observed in the bone marrow, spleen, and peripheral blood of NOD/SCID (n=23) and NOD/SCID B2M null (n=27) mice transplanted with as few as 103 ALDHhiCD133+Lin− cells, whereas transplantation of up to 2x105 ALDHhiCD133−Lin− cells produced no detectable human engraftment. BM repopulation at limiting dilution demonstrated increased NOD/SCID repopulating ability elicited by ALDHhiCD133+Lin− cells when directly compared to CD133+Lin− cells not selected for ALDH activity. Repopulating ALDHhiCD133+Lin− cells differentiated into cells expressing markers for mature myeloid (CD33, CD14) and B-lymphoid (CD19, CD20) cells. ALDHhiCD133+Lin− cells also supported the maintenance of primitive cell phenotypes up to 8 weeks post-transplantation (2.4±0.7% CD34+CD38−, 5.5±0.6% CD34+CD133+, n=6) and the repopulating function of these cells are currently being confirmed by secondary transplantation. We are also investigating the ability of ALDHhiCD133+Lin− cells to mediate tissue repair in non-hematopoietic organs. Fractionation of human HSC based on combined expression of CD133 and high ALDH activity provides a rigorous selection of purified hematopoietic stem and progenitor cells that maintain primitive characteristics after transplantation, and may be considered a potential alternative to CD34+ cell isolation.

Enforced Expression of GATA-2 Confers Quiescence on Human Hematopoietic Stem and Progenitor Cells In Vitro and In Vivo.

Blood ◽  
2006 ◽  
Vol 108 (11) ◽  
pp. 83-83
Author(s):  
Alex J. Tipping ◽  
Cristina Pina ◽  
Anders Castor ◽  
Ann Atzberger ◽  
Dengli Hong ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Progenitor Cells ◽  
Zinc Finger ◽  
Human Cord Blood ◽  
Hematopoietic Stem ◽  
Cd34 Cells ◽  
Stem And Progenitor Cells ◽  
Colony Number

Abstract Hematopoietic stem cells (HSCs) in adults are largely quiescent, periodically entering and exiting cell cycle to replenish the progenitor pool or to self-renew, without exhausting their number. Expression profiling of quiescent HSCs in our and other laboratories suggests that high expression of the zinc finger transcription factor GATA-2 correlates with quiescence. We show here that TGFβ1-induced quiescence of wild-type human cord blood CD34+ cells in vitro correlated with induction of endogenous GATA-2 expression. To directly test if GATA-2 has a causative role in HSC quiescence we constitutively expressed GATA-2 in human cord blood stem and progenitor cells using lentiviral vectors, and assessed the functional output from these cells. In both CD34+ and CD34+ CD38− populations, enforced GATA-2 expression conferred increased quiescence as assessed by Hoechst/Pyronin Y staining. CD34+ cells with enforced GATA-2 expression showed reductions in both colony number and size when assessed in multipotential CFC assays. In CFC assays conducted with more primitive CD34+ CD38− cells, colony number and size were also reduced, with myeloid and mixed colony number more reduced than erythroid colonies. Reduced CFC activity was not due to increased apoptosis, as judged by Annexin V staining of GATA-2-transduced CD34+ or CD34+ CD38− cells. To the contrary, in vitro cultures from GATA-2-transduced CD34+ CD38− cells showed increased protection from apoptosis. In vitro, proliferation of CD34+ CD38− cells was severely impaired by constitutive expression of GATA-2. Real-time PCR analysis showed no upregulation of classic cell cycle inhibitors such as p21, p57 or p16INK4A. However GATA-2 expression did cause repression of cyclin D3, EGR2, E2F4, ANGPT1 and C/EBPα. In stem cell assays, CD34+ CD38− cells constitutively expressing GATA-2 showed little or no LTC-IC activity. In xenografted NOD/SCID mice, transduced CD34+ CD38−cells expressing high levels of GATA-2 did not contribute to hematopoiesis, although cells expressing lower levels of GATA-2 did. This threshold effect is presumably due to DNA binding by GATA-2, as a zinc-finger deletion variant of GATA-2 shows contribution to hematopoiesis from cells irrespective of expression level. These NOD/SCID data suggest that levels of GATA-2 may play a part in the in vivo control of stem and progenitor cell proliferation. Taken together, our data demonstrate that GATA-2 enforces a transcriptional program on stem and progenitor cells which suppresses their responses to proliferative stimuli with the result that they remain quiescent in vitro and in vivo.

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