scholarly journals Obesity affects mitochondrial metabolism and proliferative potential of endometrial progenitor cells

2021 ◽  
Author(s):  
Agnieszka Smieszek ◽  
Klaudia Marcinkowska ◽  
Ariadna Pielok ◽  
Mateusz Sikora ◽  
Lukas Valihrach ◽  
...  
Keyword(s):  
Progenitor Cells ◽  
Mitochondrial Dynamics ◽  
Mitochondrial Metabolism ◽  
Proliferative Potential ◽  
Proliferation Capacity ◽  
Clonogenic Potential ◽  
Enhanced Expression ◽  
Functional Features ◽  
Induced Changes ◽  
Oxidative Homeostasis

AbstractThe study aimed to investigate the influence of obesity on cellular features of equine endometrial progenitor cells (Eca EPCs), including viability, proliferation capacity, mitochondrial metabolism, and oxidative homeostasis. Eca EPCs derived from non-obese (Non-OB) and obese (OB) mares were characterised by cellular phenotype and multipotency.Obesity-induced changes in the activity of Eca EPCs include the decline of their proliferative activity, clonogenic potential, mitochondrial metabolism and enhanced oxidative stress. Eca EPCs isolated from obese mares were characterised by an increased occurrence of early apoptosis, loss of mitochondrial dynamics, and senescence-associated phenotype. Attenuated metabolism of Eca EPCs OB was related to increased expression of pro-apoptotic markers (CASP9, BAX, P53, P21), enhanced expression of OPN, PI3K and AKT, simultaneously with decreased signalling stabilising cellular homeostasis (including mitofusin, SIRT1, FOXP3).Obesity alters functional features and self-renewal potential of endometrial progenitor cells. The impaired cytophysiology of progenitor cells from obese endometrium predict lower regenerative capacity if used as autologous transplants.

Skeletal Progenitor Cells and Ageing Human Populations

1998 ◽  
Vol 94 (5) ◽  
pp. 549-555 ◽  
Author(s):  
Richard O. C. Oreffo ◽  
Stéphanie Bord ◽  
James T. Triffitt
Keyword(s):  
Alkaline Phosphatase ◽  
Bone Mass ◽  
Progenitor Cells ◽  
Colony Size ◽  
Fracture Repair ◽  
Human Populations ◽  
Proliferative Potential ◽  
Primary Osteoporosis ◽  
Differentiation Potential ◽  
Colony Number

1. Stem and progenitor cells present within bone marrow give rise to colony forming units-fibroblastic (CFU-F) which can differentiate into fibroblastic, osteogenic, myogenic, adipogenic and reticular cells. The decrease in skeletal bone formation and rate of fracture repair observed with ageing and in osteoporosis has been suggested to be due to a decrease in numbers of these progenitors, but human studies are limited. 2. We have tested the potential to form CFU-F in a total of 99 patients undergoing corrective surgery (16 controls, 14–48 years of age) or hip arthroplasty for osteoarthritis (57 patients, 28–87 years of age) or osteoporosis (26 patients, 69–97 years of age). Total colony number, alkaline phosphatase-positive colony number and colony size were determined. 3. No decrease in colony forming efficiency under the culture conditions used was observed in all populations examined irrespective of age, disease or gender, as determined by the lack of correlation between colony formation and age. 3. Examination of colony sizes showed a significant reduction in colony size with age in osteoarthritis and in control populations indicating a change in cellular proliferative potential with age. 4. Examination of number and percentage of alkaline phosphatase-positive CFU-F showed a significant decrease in osteoporotic patients compared with controls and osteoarthritis patients, indicating altered differentiation potential. 5. These results suggest that the reduction in bone mass with ageing may be due to reduction of the proliferative capacity of progenitor cells or their responsiveness to biological factors leading to alteration in subsequent differentiation. The maintenance of CFU-F number and alkaline phosphatase activity in these osteoarthritis patients may, in part, explain the inverse relationship observed for the preservation of bone mass between generalized osteoarthritis and primary osteoporosis.

Hepatic stem/progenitor cells with high proliferative potential in liver organ formation

2001 ◽  
Vol 33 (1-2) ◽  
pp. 585-586 ◽  
Author(s):  
A Suzuki ◽  
Y.-W Zheng ◽  
K Fukao ◽  
H Nakauchi ◽  
H Taniguchi
Keyword(s):  
Progenitor Cells ◽  
Proliferative Potential ◽  
Organ Formation

scholarly journals Identification of a Serpin Specifically Expressed in Multipotent and Bipotent Hematopoietic Progenitor Cells and in Activated T Cells

Blood ◽  
1997 ◽  
Vol 89 (1) ◽  
pp. 108-118
Author(s):  
I.N. Hampson ◽  
L. Hampson ◽  
M. Pinkoski ◽  
M. Cross ◽  
C.M. Heyworth ◽  
...  
Keyword(s):  
T Cells ◽  
Progenitor Cells ◽  
Cd8 T Cells ◽  
Fetal Liver ◽  
Constitutive Expression ◽  
Hematopoietic Progenitor ◽  
Macrophage Differentiation ◽  
Activated T Cells ◽  
Clonogenic Potential ◽  
High Level

We have identified a gene that has a high level of mRNA expression in undifferentiated, multipotential hematopoietic cells (FDCP-Mix) and that downregulates both transcript and protein, as these cells are induced to differentiate into mature myeloid cells. Sequence analysis of this gene has identified it as a serine protease inhibitor EB22/3 (serpin 2A). Constitutive expression of serpin 2A in FDCP-Mix cells was associated with an increase in the clonogenic potential of the cells and with a delay in the appearance of fully mature cells in cultures undergoing granulocyte macrophage differentiation when compared with control cells. Serpin 2A was also found to be expressed in bone marrow-derived bipotent granulocyte macrophage progenitor cells (GM-colony forming cell [CFC]), but not in erythrocyte progenitor cells from day 15 fetal liver. Expression of serpin 2A also showed a marked up regulation during the activation of cytotoxic suppressor CD8+ T cells, with a clear lag between the appearance of transcript and detection of protein.

scholarly journals Hematopoietic stem/progenitor cells, generation of induced pluripotent stem cells, and isolation of endothelial progenitors from 21- to 23.5-year cryopreserved cord blood

Blood ◽  
2011 ◽  
Vol 117 (18) ◽  
pp. 4773-4777 ◽  
Author(s):  
Hal E. Broxmeyer ◽  
Man-Ryul Lee ◽  
Giao Hangoc ◽  
Scott Cooper ◽  
Nutan Prasain ◽  
...  
Keyword(s):  
Stem Cells ◽  
Cord Blood ◽  
Progenitor Cells ◽  
Proliferative Potential ◽  
Hematopoietic Stem ◽  
Immunodeficient Mice ◽  
Induced Pluripotent

Abstract Cryopreservation of hematopoietic stem cells (HSCs) and hematopoietic progenitor cells (HPCs) is crucial for cord blood (CB) banking and transplantation. We evaluated recovery of functional HPC cryopreserved as mononuclear or unseparated cells for up to 23.5 years compared with prefreeze values of the same CB units. Highly efficient recovery (80%-100%) was apparent for granulocyte-macrophage and multipotential hematopoietic progenitors, although some collections had reproducible low recovery. Proliferative potential, response to multiple cytokines, and replating of HPC colonies was extensive. CD34+ cells isolated from CB cryopreserved for up to 21 years had long-term (≥ 6 month) engrafting capability in primary and secondary immunodeficient mice reflecting recovery of long-term repopulating, self-renewing HSCs. We recovered functionally responsive CD4+ and CD8+ T lymphocytes, generated induced pluripotent stem (iPS) cells with differentiation representing all 3 germ cell lineages in vitro and in vivo, and detected high proliferative endothelial colony forming cells, results of relevance to CB biology and banking.

Murine pluripotent hematopoietic progenitors constitutively expressing a normal erythropoietin receptor proliferate in response to erythropoietin without preferential erythroid cell differentiation

1994 ◽  
Vol 14 (7) ◽  
pp. 4834-4842
Author(s):  
A Dubart ◽  
F Feger ◽  
C Lacout ◽  
F Goncalves ◽  
W Vainchenker ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Progenitor Cells ◽  
Bone Marrow Cells ◽  
Erythropoietin Receptor ◽  
Erythroid Cell ◽  
Major Influence ◽  
Proliferative Potential ◽  
Steel Factor ◽  
Interleukin 3 ◽  
Marrow Cells

Erythropoietin (EPO) is a prime regulator of the growth and differentiation of erythroid blood cells. The EPO receptor (EPO-R) is expressed in late erythroid progenitors (mature BFU-E and CFU-E), and EPO induces proliferation and differentiation of these cells. By introducing, with a retroviral vector, a normal EPO-R cDNA into murine adult bone marrow cells, we showed that EPO is also able to induce proliferation in pluripotent progenitor cells. After 7 days of coculture with virus-producing cells, bone marrow cells were plated in methylcellulose culture in the presence of EPO, interleukin-3, or Steel factor alone or in combination. In the presence of EPO alone, EPO-R virus-infected bone marrow cells gave rise to mixed colonies comprising erythrocytes, granulocytes, macrophages and megakaryocytes. The addition of interleukin-3 or Steel factor to methylcellulose cultures containing EPO did not significantly modify the number of mixed colonies. The cells which generate these mixed colonies have a high proliferative potential as shown by the size and the ability of the mixed colonies to give rise to secondary colonies. Thus, it appears that EPO has the same effect on EPO-R-expressing multipotent cell proliferation as would a combination of several growth factors. Finally, our results demonstrate that inducing pluripotent progenitor cells to proliferate via the EPO signaling pathway has no major influence on their commitment.

scholarly journals Specific growth inhibition of primitive hematopoietic progenitor cells mediated through monoclonal antibody binding to major histocompatibility class II molecules

Blood ◽  
1992 ◽  
Vol 80 (8) ◽  
pp. 1950-1956 ◽  
Author(s):  
HT Greinix ◽  
R Storb ◽  
SH Bartelmez
Keyword(s):  
Monoclonal Antibody ◽  
Progenitor Cells ◽  
Class Ii ◽  
Canine Model ◽  
Proliferative Potential ◽  
Continuous Exposure ◽  
Hematopoietic Growth Factors ◽  
Hla Dr ◽  
Marrow Cells

Abstract In a previous study using a canine model, we reported that a certain anti-class II monoclonal antibody (MoAb H81.9), which recognizes an epitope formed by the alpha and beta subunits of HLA-DR, prevented long- term engraftment of autologous marrow cells if administered intravenously during the first 4 days after 9.2 Gy of total body irradiation. Another MoAb (B1F6), reactive with only the beta subunit of HLA-DR and -DP, had no adverse effect on engraftment, although both MoAbs detect antigens on hematopoietic long-term repopulating cells as determined from complement-mediated lysis experiments. In the present study, continuous exposure of unfractionated human marrow to MoAb H81.9 specifically inhibited the growth of primitive progenitor cells that require multiple hematopoietic growth factors for proliferation (high proliferative potential colony forming cells [HPP-CFC] and burst- forming units-erythroid [BFU-e]), but had no effect on more mature, single factor responsive (CFU-GM), progenitor cells. In contrast, MoAb B1F6 did not impair primitive progenitor cell growth cultured as unfractionated marrow. However, when cell dose-response experiments were performed using CD34-positive cells plated at low cell densities, the marked inhibitory effects of MoAb H81.9 on HPP-CFC and BFU-e colony formation were not seen. These findings suggest that MoAb H81.9 may not inhibit primitive hematopoietic cells directly, but rather indirectly through the action of potent mediators derived from other HLA-DR- positive marrow cells.

scholarly journals Long-term generation and expansion of human primitive hematopoietic progenitor cells in vitro

Blood ◽  
1993 ◽  
Vol 81 (3) ◽  
pp. 661-669 ◽  
Author(s):  
EF Srour ◽  
JE Brandt ◽  
RA Briddell ◽  
S Grigsby ◽  
T Leemhuis ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Progenitor Cells ◽  
Bone Marrow Cells ◽  
Fold Increase ◽  
Hematopoietic Progenitor Cells ◽  
Proliferative Potential ◽  
Hematopoietic Progenitor ◽  
Hla Dr

Abstract Although sustained production of committed human hematopoietic progenitor cells in long-term bone marrow cultures (LTBMC) is well documented, evidence for the generation and expansion of human primitive hematopoietic progenitor cells (PHPC) in such cultures is lacking. For that purpose, we attempted to determine if the human high proliferative potential colony-forming cell (HPP-CFC), a primitive hematopoietic marrow progenitor cell, is capable of generation and expansion in vitro. To that effect, stromal cell-free LTBMC were initiated with CD34+ HLA-DR-CD15- rhodamine 123dull bone marrow cells and were maintained with repeated addition of c-kit ligand and a synthetic interleukin-3/granulocyte-macrophage colony-stimulating factor fusion protein. By day 21 of LTBMC, a greater than twofold increase in the number of assayable HPP-CFC was detected. Furthermore, the production of HPP-CFC in LTBMC continued for up to 4 weeks, resulting in a 5.5-fold increase in HPP-CFC numbers. Weekly phenotypic analyses of cells harvested from LTBMC showed that the number of CD34+ HLA-DR- cells increased from 10(4) on day 0 to 56 CD34+ HLA-DR- cells increased from 10(4) on day 0 to 56 x 10(4) by day 21. To examine further the nature of the in vitro HPP-CFC expansion, individual HPP- CFC colonies were serially cloned. Secondary cloning of individual, day 28 primary HPP-CFC indicated that 46% of these colonies formed an average of nine secondary colony-forming unit--granulocyte-macrophage (CFU-GM)--derived colonies, whereas 43% of primary HPP-CFC gave rise to between one and six secondary HPP-CFC colonies and 6 to 26 CFU-GM. These data show that CD34+ HLA-DR- CD15- rhodamine 123dull cells represent a fraction of human bone marrow highly enriched for HPP-CFC and that based on their regeneration and proliferative capacities, a hierarchy of HPP-CFC exists. Furthermore, these studies indicate that in the presence of appropriate cytokine stimulation, it is possible to expand the number of PHPC in vitro.

scholarly journals Virally induced changes in cellular microRNAs maintain latency of human cytomegalovirus in CD34+ progenitors

2011 ◽  
Vol 92 (7) ◽  
pp. 1539-1549 ◽  
Author(s):  
Emma Poole ◽  
Stuart R. McGregor Dallas ◽  
Julia Colston ◽  
Robert Samuel V. Joseph ◽  
John Sinclair
Keyword(s):  
Gene Expression ◽  
Progenitor Cells ◽  
Human Cytomegalovirus ◽  
Human Herpesvirus ◽  
Cellular Mirnas ◽  
Viral Genomes ◽  
Cell Gene Expression ◽  
Induced Changes ◽  
Cell Gene ◽  
Stem Cell Gene

One site of latency of human cytomegalovirus (HCMV; human herpesvirus 5) is known to be CD34+ haematopoietic progenitor cells, and it is likely that carriage of latent virus has profound effects on cellular gene expression in order to optimize latency and reactivation. As microRNAs (miRNAs) play important roles in regulating stem-cell gene expression, this study asked whether latent carriage of HCMV led to changes in cellular miRNA expression. A comprehensive miRNA screen showed the differential regulation of a number of cellular miRNAs during HCMV latency in CD34+ progenitor cells. One of these, hsa-miR-92a, was robustly decreased in three independent miRNA screens. Latency-induced change in hsa-miR-92a results in an increase in expression of GATA-2 and subsequent increased expression of cellular IL-10, which aids the maintenance of latent viral genomes in CD34+ cells, probably resulting from their increased survival.

Perspectives of pharmacological intervention promoting liver regeneration

2018 ◽  
Vol 2 (1) ◽  
pp. 5-8 ◽  
Author(s):  
Irina G. Danilova ◽  
Hanna Kalota ◽  
Musa T. Abidov
Keyword(s):  
Liver Regeneration ◽  
Progenitor Cells ◽  
Liver Diseases ◽  
Animal Studies ◽  
Pharmacological Intervention ◽  
Proliferative Potential ◽  
Liver Disorders ◽  
Liver Functions ◽  
Injured Liver ◽  
Pharmacological Control

Effective drug therapy promoting liver regeneration is a challenging goal in pharmacotherapy of liver diseases. Several plant phytochemicals recommended in traditional medicine from over hundred plants have been investigated for its use in various liver disorders. Regeneration of injured liver depend on a proliferative potential of mature hepatocytes as well as different subsets of intrahepatic and extrahepatic stem/progenitor cells. In clinical trials a stem cell therapy resulted in a limited improvement of liver functions. Animal studies have demonstrated the involvement of bone marrow-derived stem/progenitor cells in liver regeneration. For this reason, the pharmacological activation of endogenous stem cells and pharmacological control of macrophage phenotypic polarization could be an effective method of mobilizing progenitor cells to injured liver.

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