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.

scholarly journals Tendon-Derived Progenitor Cells With Multilineage Potential Are Present Within Human Patellar Tendon

2021 ◽  
Vol 9 (8) ◽  
pp. 232596712110234
Author(s):  
Erika A. Leonardi ◽  
Michelle Xiao ◽  
Iain R. Murray ◽  
William H. Robinson ◽  
Geoffrey D. Abrams
Keyword(s):  
Alkaline Phosphatase ◽  
Transcription Factor ◽  
Progenitor Cells ◽  
Patellar Tendon ◽  
Cell Culture Supernatant ◽  
Enzyme Linked Immunosorbent Assay ◽  
Medical Procedure ◽  
Alizarin Red ◽  
Differentiation Potential ◽  
Promising Source

Background: Progenitor cells serve as a promising source of regenerative potential in a variety of tissue types yet remain underutilized in tendinopathy. Tendon-derived progenitor cells (TDPCs) have previously been isolated from hamstring tendon but only as part of a concomitant medical procedure. Determining the presence of TDPCs in patellar tendon may facilitate clinical utilization of these cells because of the relative accessibility of this location for tissue harvest. Purpose: To characterize TDPCs in human patellar tendon samples. Study Design: Descriptive laboratory study. Methods: Human patellar tendon samples were obtained during elective knee surgery. TDPCs were isolated and seeded at an optimal low cell density and subcultured to confluence for up to 2 passages. Flow cytometry was used to analyze for the expression of CD90+, CD105+, CD44+, and CD31–, CD34–, and CD45– markers. The multilineage differentiation potential of TDPCs was tested in vitro via adipogenic, osteogenic, and chondrogenic culture with subsequent cytochemical staining for Oil Red O, Alizarin Red, and Alcian Blue, respectively. Enzyme-linked immunosorbent assay was used to quantify the amount of adiponectin, alkaline phosphatase, and SRY-box transcription factor 9 secreted into cell culture supernatant for further confirmation of lineage differentiation. Results were analyzed statistically using the 2-tailed Student t test. Results: TDPCs demonstrated near-uniform expression of CD90, CD105, and CD44 with minimal expression of CD34, CD31, and CD45. Adipogenic, osteogenic, and chondrogenic differentiation of TDPCs was confirmed using qualitative analysis. The expression of adiponectin, alkaline phosphatase, and SRY-box transcription factor 9 were significantly increased in differentiated cells versus undifferentiated TDPCs ( P < .05). Conclusion: TDPCs can be successfully isolated from human patellar tendon samples, and they exhibit characteristics of multipotent progenitor cells. Clinical Relevance: These data demonstrate the promise of patellar tendon tissue as a source of progenitor cells for use in biologic therapies for the treatment of tendinopathy.

C/EBPα deficiency results in hyperproliferation of hematopoietic progenitor cells and disrupts macrophage development in vitro and in vivo

Blood ◽  
2004 ◽  
Vol 104 (6) ◽  
pp. 1639-1647 ◽  
Author(s):  
Victoria Heath ◽  
Hyung Chan Suh ◽  
Matthew Holman ◽  
Katie Renn ◽  
John M. Gooya ◽  
...  
Keyword(s):  
Progenitor Cells ◽  
Fetal Liver ◽  
Cell Types ◽  
Hematopoietic Progenitor Cells ◽  
Proliferative Potential ◽  
Hematopoietic Growth Factors ◽  
Hematopoietic Progenitor ◽  
Differentiation Potential

Abstract CCAAT enhancer binding protein-α (C/EBPα) inhibits proliferation in multiple cell types; therefore, we evaluated whether C/EBPα-deficient hematopoietic progenitor cells (HPCs) have an increased proliferative potential in vitro and in vivo. In this study we demonstrate that C/EBPα-/- fetal liver (FL) progenitors are hyperproliferative, show decreased differentiation potential, and show increased self-renewal capacity in response to hematopoietic growth factors (HGFs). There are fewer committed bipotential progenitors in C/EBPα-/- FL, whereas multipotential progenitors are unaffected. HGF-dependent progenitor cell lines can be derived by directly culturing C/EBPα-/- FL cells in vitro Hyperproliferative spleen colonies and myelodysplastic syndrome (MDS) are observed in mice reconstituted with C/EBPα-/- FL cells, indicating progenitor hyperproliferation in vitro and in vivo. C/EBPα-/- FL lacked macrophage progenitors in vitro and had impaired ability to generate macrophages in vivo. These findings show that C/EBPα deficiency results in hyperproliferation of HPCs and a block in the ability of multipotential progenitors to differentiate into bipotential granulocyte/macrophage progenitors and their progeny. (Blood. 2004; 104:1639-1647)

Abstract P014: Oxidative Stress Mediated Regulation of Antioxidants in Cardiac Progenitor Cells

2011 ◽  
Vol 109 (suppl_1) ◽  
Author(s):  
Gokulakrishnan Iyer ◽  
Michael E Davis
Keyword(s):  
Oxidative Stress ◽  
Xanthine Oxidase ◽  
Progenitor Cells ◽  
Cardiac Progenitor Cells ◽  
Dependent Manner ◽  
Akt Inhibitor ◽  
Differentiation Potential ◽  
Lineage Differentiation ◽  
Phosphorylated Akt

Cardiac diseases are the leading causes of death throughout the world and transplantation of endogenous myocardial progenitor population with robust cardiovascular lineage differentiation potential is a promising therapeutic strategy. Therefore, in vitro expansion and transplantation of cardiac progenitor cells (CPCs) is currently in early clinical testing as a potential treatment for severe cardiac dysfunction. However, poor survival and engraftment of cells is one of the major limitations of cell transplantation therapy. Oxidative stress is increased in the ischemic myocardium and indirect inferences suggest the vulnerability of CPCs to oxidative stress. In this study, we show that in vitro, resident c-kit positive CPCs isolated from rat myocardium are significantly (p<0.05) resistant to superoxide-induced apoptosis compared to cardiomyocytes as analyzed by the number of sub-G1 population following xanthine/xanthine oxidase treatment. Interestingly, CPCs have two to four fold higher basal SOD1 and SOD2 activities (p<0.01) compared to cardiomyocytes and endothelial cells. Superoxide treatment increased expression of SOD1 (p<0.01), SOD2 (p<0.01), and glutathione peroxidase (p<0.05) mRNAs within 6 h of treatment compared to control cells. Recent studies suggest the involvement of AKT in controlling cell death, survival and also expression of SOD enzymes. Therefore, we investigated the involvement of AKT in CPCs subjected to oxidative stress. Western blot analysis revealed that the amount of phosphorylated AKT increased significantly within 10 minutes of xanthine/xanthine oxidase treatment. In addition, treatment with LY294002 - a PI3 kinase/AKT inhibitor, increased apoptosis in CPCs treated with superoxide. Our studies demonstrate a novel finding in which resident progenitor cells are protected from oxidative injury by containing higher basal levels of antioxidants as compared to myocytes. Moreover, under oxidant challenge antioxidant levels are regulated, possibly in an AKT-dependent manner. Further elucidation of this pathway may lead to novel therapeutic opportunities.

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

Progenitor Cells in Embryonic and Post-Natal Rat Livers, Their Growth and Differentiation Potential

1993 ◽  
pp. 58-65 ◽  
Author(s):  
Normand Marceau ◽  
Claude Chamberland ◽  
Marie-Josée Blouin ◽  
Micheline Noël ◽  
Anne Loranger
Keyword(s):  
Progenitor Cells ◽  
Differentiation Potential ◽  
Rat Livers
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