Lack of telomerase activity in human mesenchymal stem cells

Zimmermann, Stefan; Voss, Martina; Kaiser, S.; Kapp, Ursula; Waller, Christiane; Martens, Uwe M.

doi:10.1038/sj.leu.2402962

Cited by 244 publications

(178 citation statements)

References 28 publications

(25 reference statements)

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“…The catalytic subunit of telomerase, hTERT, was not detected in our hMSC cultures, and hence it must be concluded that our cells also lack activity of this enzyme. Some groups reported expression and activity of telomerase in MSC [6,38], while others could not detect the enzyme [39]. Interestingly, stable transfection with the telomerase gene led to immortalization of MSC without any influence on their differentiation potential [40].…”

Section: Characterization Of the Cellsmentioning

confidence: 99%

5-Azacytidine induces changes in electrophysiological properties of human mesenchymal stem cells

et al. 2006

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Previously, mouse bone marrow-derived stem cells (MSC) treated with the unspecific DNA methyltransferase inhibitor 5-azacytidine were reported to differentiate into cardiomyocytes. The aim of the present study was to investigate the efficiency of a similar differentiation strategy in human mononuclear cells obtained from healthy bone marrow donors. After 1-3 passages, cultures were exposed for 24 h to 5-azacytidine (3 µM) followed by 6 weeks of further culture. Drug treatment did not induce expression of myogenic marker MyoD or cardiac markers Nkx2.5 and GATA-4 and did not yield beating cells during follow-up. In patch clamp experiments, approximately 10-15% of treated and untreated cells exhibited L-type Ca 2+ currents. Almost all cells showed outwardly rectifying K + currents of rapid or slow activation kinetics. Mean current amplitude at +60 mV doubled after 6 weeks of treatment compared with time-matched controls. Membrane capacitance of treated cells was significantly larger than in controls 2 weeks after treatment and remained high after 6 weeks. Expression levels of mRNAs for the K + channels Kv1.1, Kv1.5, Kv2.1, Kv4.3 and KCNMA1 and for the Ca 2+ channel Ca v 1.2 were not affected by 5-azacytidine. Treatment with potassium channel blockers tetraethylammonium and clofilium at concentrations shown previously to inhibit rapid or slowly activating K + currents of hMSC inhibited proliferation of these cells. Our results suggest that despite the absence of differentiation of hMSC into cardiomyocytes, treatment with 5-azacytidine caused profound changes in current density.Cell Research (2006) 16:949-960.

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Section: Characterization Of the Cellsmentioning

confidence: 99%

5-Azacytidine induces changes in electrophysiological properties of human mesenchymal stem cells

et al. 2006

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“…The differences in expandability may be explained by telomere length and telomerase activity (20)(21)(22), although some studies have indicated that telomerase activity does not occur in MSCs during expansion (23).…”

mentioning

confidence: 99%

Comparison of human stem cells derived from various mesenchymal tissues: Superiority of synovium as a cell source

Sakaguchi¹,

Sekiya²,

Yagishita³

et al. 2005

Arthritis & Rheumatism

1,369

1,171

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Objective. To compare the properties of human mesenchymal stem cells (MSCs) isolated from bone marrow, synovium, periosteum, skeletal muscle, and adipose tissue.Methods. Human mesenchymal tissues were obtained from 8 donors during knee surgery for ligament injury. After collagenase digestion or gradient-density separation, nucleated cells were plated at an appropriate density for expansion at the maximum rate without colony-to-colony contact. Yield, expandability, differentiation potential, and epitope profile were compared among MSCs from the 5 different tissue sources.Results. Colony number per 10 3 nucleated cells was lower, and cell number per colony was higher, in bone marrow than in other mesenchymal tissues. When the cells were replated at low density every 14 days, bone marrow-, synovium-, and periosteum-derived cells retained their proliferation ability even at passage 10. In chondrogenesis studies in which the cells were pelleted and cultured in vitro, pellets from bone marrow-, synovium-, and periosteum-derived cells were shown to be larger and stained more extensively for cartilage matrix. Synovium-derived cells, in particular, had the greatest ability for chondrogenesis. In adipogenesis experiments, the frequency of oil red O-positive colonies was highest in synovium-and adipose tissue-derived cells. In studies of osteogenesis, the rate of alizarin red-positive colonies was highest in bone marrow-, synovium-, and periosteum-derived cells. For epitope profiling, 15 surface antigens were measured. Most appeared to have similar epitope profiles irrespective of cell source.Conclusion. Our findings indicate that there are significant differences in MSC properties according to tissue source, beyond donor and experimental variation. Superiority of synovium as a potential source of MSCs for clinical applications was demonstrated.

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“…By way of comparison, plant stem cells such as the Arabidopsis meristem often contain detectable telomerase activity (Riha et al, 2001). However, not all human stem cell populations contain active telomerase; for example, mesenchymal stem cells retain the ability to regenerate multiple lineages including stromal cells and chondrocytes, and yet telomerase activity cannot be detected above background levels in some instances (Table 1) (Banfi et al, 2002;Gronthos et al, 2003;Zimmermann et al, 2003;Parsch et al, 2004). In these populations, it is not yet completely clear whether telomeres undergo the usual attrition in the absence of telomerase activity (Banfi et al, 2002;Gronthos et al, 2003;Zimmermann et al, 2003;Parsch et al, 2004).…”

Section: Telomerase Activity In Stem Cellsmentioning

confidence: 99%

Does the reservoir for self-renewal stem from the ends?

Harrington

2004

Oncogene

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Stem cell research is a burgeoning field with an alluring potential for therapeutic intervention, and thus begs a critical understanding of the long-term consequences of stem cell replacement. Operationally, a stem cell may be defined as a rarely dividing cell with the capacity for selfrenewal throughout the lifetime of the organism, and an ability to reconstitute its appropriate lineages via proliferation and differentiation. In many differentiated normal and cancer cell types, the maintenance of telomeres plays a pivotal role in their continued division potential. Taken together with the presence of the enzymatic activity responsible for telomere addition, telomerase, in several progenitor cell lineages, it is presumed that telomere maintenance will be critical for the replenishment of stem cells or their successors. The purpose of this review is to discuss the role of telomere length maintenance in self-renewal, and the consequent challenges and potential pitfalls to the manipulation of normal and cancer-derived stem cells.

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Lack of telomerase activity in human mesenchymal stem cells

Cited by 244 publications

References 28 publications

5-Azacytidine induces changes in electrophysiological properties of human mesenchymal stem cells

5-Azacytidine induces changes in electrophysiological properties of human mesenchymal stem cells

Comparison of human stem cells derived from various mesenchymal tissues: Superiority of synovium as a cell source

Does the reservoir for self-renewal stem from the ends?

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