Abstract:Background-Even though telomerase activity has been analyzed in various normal and malignant tissues, including liver, it is still unknown to what extent telomerase can be associated with specific maturational lineage stages.
“…Dysregulation of telomerase activity results in uncontrolled malignant tumor growth [Dhaene et al, 2000]. Several studies have shown that cancer cells also have increased telomerase activity which stops telomere shortening and enhances their self‐renewal ability and resistance to apoptosis, effectively rendering them immortal [Fujiwara, 2009; Proctor et al, 2009; Schmelzer and Reid, 2009; Shaker et al, 2009].…”
This study aimed to determine the cellular aging of osteophyte-derived mesenchymal cells (oMSCs) in comparison to patient-matched bone marrow stromal cells (bMSCs). Extensive expansion of the cell cultures was performed and early and late passage cells (passages 4 and 9, respectively) were used to study signs of cellular aging, telomere length, telomerase activity, and cell-cycle-related gene expression. Our results showed that cellular aging was more prominent in bMSCs than in oMSCs, and that oMSCs had longer telomere length in late passages compared with bMSCs, although there was no significant difference in telomere lengths in the early passages in either cell type. Telomerase activity was detectable only in early passage oMSCs and not in bMSCs. In osteophyte tissues telomerase-positive cells were found to be located perivascularly and were Stro-1 positive. Fifteen cell-cycle regulator genes were investigated and only three genes (APC, CCND2, and BMP2) were differentially expressed between bMSC and oMSC. Our results indicate that oMSCs retain a level of telomerase activity in vitro, which may account for the relatively greater longevity of these cells, compared with bMSCs, by preventing replicative senescence.
“…Dysregulation of telomerase activity results in uncontrolled malignant tumor growth [Dhaene et al, 2000]. Several studies have shown that cancer cells also have increased telomerase activity which stops telomere shortening and enhances their self‐renewal ability and resistance to apoptosis, effectively rendering them immortal [Fujiwara, 2009; Proctor et al, 2009; Schmelzer and Reid, 2009; Shaker et al, 2009].…”
This study aimed to determine the cellular aging of osteophyte-derived mesenchymal cells (oMSCs) in comparison to patient-matched bone marrow stromal cells (bMSCs). Extensive expansion of the cell cultures was performed and early and late passage cells (passages 4 and 9, respectively) were used to study signs of cellular aging, telomere length, telomerase activity, and cell-cycle-related gene expression. Our results showed that cellular aging was more prominent in bMSCs than in oMSCs, and that oMSCs had longer telomere length in late passages compared with bMSCs, although there was no significant difference in telomere lengths in the early passages in either cell type. Telomerase activity was detectable only in early passage oMSCs and not in bMSCs. In osteophyte tissues telomerase-positive cells were found to be located perivascularly and were Stro-1 positive. Fifteen cell-cycle regulator genes were investigated and only three genes (APC, CCND2, and BMP2) were differentially expressed between bMSC and oMSC. Our results indicate that oMSCs retain a level of telomerase activity in vitro, which may account for the relatively greater longevity of these cells, compared with bMSCs, by preventing replicative senescence.
“…Telomeres may shorten through the advancement of age, as well as other processes that damage the cell . Telomerase activity may help to abrogate this change by adding telomeric repeats on to the end of chromosomes, but it appears that this only occurs in foetal livers . Four groups have studied the relationship between telomere length and ageing in humans …”
Section: Telomeresmentioning
confidence: 99%
“…21,22 Telomerase activity may help to abrogate this change by adding telomeric repeats on to the end of chromosomes, but it appears that this only occurs in foetal livers. 23 Four groups have studied the relationship between telomere length and ageing in humans. 6,[24][25][26] In one of the first studies of telomeres in human liver samples derived from liver resections, Aikata et al reported a reduction rate of 120 bp in 23 individuals (aged 17-81 years) with telomere length reducing to 10 kbp at the age of 80.…”
There are many factors that play a role in the ageing of the liver. Further studies into biomarkers of ageing and their relationship to the chronological age of the liver are required to aid in predicting long-term graft survival and utilization of organs.
“…Toutefois le phénotype des cellules isolées n'est pas encore complètement défini. De plus, l'activité télomérase mise en évidence dans les foies foetaux est inexistante dans les cellules souches dérivées des foies nouveau-nés [42].…”
Section: Autres Types De Cellules Souches Sources Potentielles D'hépaunclassified
Le foie est le siège de nombreux déficits métaboli-ques (maladies du cycle de l'urée, hypercholestéro-lémie familiale, syndrome de Crigler-Najjar type I, etc.), mais aussi la cible d'atteintes hépatiques chroniques ou aiguës. Actuellement la transplantation > La transplantation d'hépatocytes est considérée comme une alternative à la transplantation d'organes pour le traitement de maladies métaboliques notamment. Cependant, en raison des difficultés de disposer d'un grand nombre d'hépatocytes, de nouvelles sources de cellules ont été envisagées. Ces cellules peuvent être d'origine hépatique (cellules souches hépatiques) ou extra-hépatique, telles les cellules souches mésenchymateuses ou les cellules souches pluripotentes (cellules souches embryonnaires humaines [CSEh] ou iPS). Nous avons mis au point une méthode de diffé-renciation des CSEh en hépatocytes foetaux. Les conditions de différenciation qui reproduisent les étapes majeures du développement embryonnaire du foie sont établies en milieu défini, sans ajout de produit d'origine animale ou indéterminée. Les cellules obtenues expriment de nombreux marqueurs d'hépatocytes foetaux (cytochrome p450 3A7, albumine, alpha-1-antitrypsine, etc.). Elles sont capables d'assurer des fonctions spécifiques des hépatocytes (métaboliser l'ammonium, excré-ter le vert d'indocyanine), et enfin de se dévelop-per et d'exprimer des protéines hépatiques deux mois après transplantation dans le foie de souris nouveau-nés immunodéficientes (uPAxrag2gc -/-). Nous avons également démontré que ce protocole s'appliquait également aux iPS, et les études dans les modèles animaux nous permettront de comparer le potentiel in vivo de ces deux sources de cellules pluripotentes. Seules des approches précliniques effectuées chez le primate permettront de valider une éventuelle application à l'homme. < ortho topique est le seul traitement curatif des maladies métaboliques sévères engageant le pronostic vital mais elle est restreinte par la pénurie croissante de donneurs d'organe. La thérapie cellulaire apparaît depuis quelques années comme une alternative thérapeutique pour le traitement de ces maladies. En effet, elle permettrait de remplacer les seuls hépatocytes porteurs d'un défaut génétique, en laissant intact le foie. L'obstacle majeur de cette approche est que les hépatocytes ne peuvent pas être amplifiés en culture et résistent mal à la congélation. Il est donc nécessaire d'évaluer le potentiel d'autres sources de cellules, qui non seulement pourraient se différencier en hépatocytes mais aussi proliférer in vitro. Ces deux propriétés caractérisent les cellules souches pluripotentes, et en particulier les cellules souches embryonnaires et les iPS (induced pluripotent stem cells). Nous faisons le point dans cette revue sur les progrès réalisés dans l'obtention d'hépatocytes fonctionnels à partir de cellules souches pluripotentes en nous fondant sur l'expérience de notre équipe dans ce domaine.
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