Variations in the stromal cell population of human bone marrow during aging

Mets, Tony; Verdonk, G

doi:10.1016/0047-6374(81)90006-3

Cited by 47 publications

(13 citation statements)

References 27 publications

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“…In this study, an inverse correlation between normal human CFE and donor age was observed. This is in agreement with the majority of earlier publications (D'Ippolito et al, 1999; Galotto et al, 1999; Kolesnikova et al, 1978; Mets and Verdonk, 1981; Nishida et al, 1999; Rogova et al, 1981), but contradicts several others (Oreffo et al, 1998a, 1998b; Stenderup et al, 2001). The slight decrease that we noted with aging may be related to a slower rate of fracture healing in the elderly.…”

Section: Discussionsupporting

confidence: 92%

Enumeration of the colony-forming units–fibroblast from mouse and human bone marrow in normal and pathological conditions

et al. 2009

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Bone marrow stromal cell populations, containing a subset of multipotential skeletal stem cells, are increasingly contemplated for use in tissue engineering and stem cell therapy, whereas their involvement in the pathogenetic mechanisms of skeletal disorders is far less recognized. We compared the concentrations of stromal clonogenic cells, colony forming units–fibroblast (CFU-Fs), in norm and pathology. Initially, culture conditions were optimized by demonstrating that fetal bovine serum heat inactivation could significantly repress colony formation. Using non-heat-inactivated fetal bovine serum, the concentration of CFU-Fs (colony-forming efficiency, CFE) ranged from 3.5 ± 1.0 to 11.5 ± 4.0 per 1 × 105 nucleated cells in five inbred mouse strains. In four transgenic lines with profound bone involvement, CFE was either significantly reduced or increased compared to wild-type littermates. In normal human donors, CFE decreased slightly with age and averaged 52.2 ± 4.1 for children and 32.3 ± 3.0 for adults. CFE was significantly altered in patients with several skeletal, metabolic, and hematological disorders: reduced in congenital generalized lipodystrophy, achondroplasia (SADDAN), pseudoachondroplasia, and Paget disease of bone and elevated in alcaptonuria and sickle cell anemia. Our findings indicate that under appropriate culture conditions, CFE values may provide useful insights into bone/bone marrow pathophysiology.

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Section: Discussionsupporting

confidence: 92%

Enumeration of the colony-forming units–fibroblast from mouse and human bone marrow in normal and pathological conditions

et al. 2009

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“…Although some earlier reports described a parallelism between in vitro and in vivo aging cell populations (Schneider and Mitsui 1976;Mets and Verdonk 1981;Mets et al 1983), a more recent, large analysis failed to show a reduced proliferation capacity of cells explanted from elderly humans (Smith et al 2002). This observation, however, does not exclude that non dividing, senescent cells might accumulate with aging.…”

Section: Introductionmentioning

confidence: 78%

Cellular aging and senescence characteristics of human T-lymphocytes

et al. 2011

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CD28-, CD57+ and KLRG1+ are cell surface markers that have been used to describe senescent T-lymphocytes in humans. However, the relationship among these phenotypes during aging, and their relationship with the concept of in vitro cellular aging have not been well established. Using five-colour flow cytometry, we analyzed peripheral blood T-lymphocytes for their expression of CD28, CD57 and KLRG1 in 11 young (Y) and 11 old (O) apparently healthy human subjects. The proportions of CD28- and CD57+ cells were significantly higher among the T-cell populations of O compared to Y subjects; the proportion of KLRG1+ cells was significantly higher only among CD8+ cells. Populations that were more frequent in the elderly participants were characterised as CD28+ CD57+, CD28- CD57+ or CD28- CD57-. The expression of p16 and p21, considered as markers for in vitro senescence, was higher in CD28+ CD57+ cells than in other subpopulations in both age groups. The expression of p21 was age-related, which was not the case for p16. Thus, although both p16 and p21 are involved in T-cell senescence, they appear to behave differently. CMV infection and shifts in subpopulations are unlikely as explanations of the observed differences. Their higher levels of p16 and p21 expression, coupled with their higher prevalence in the elderly participants make CD28+ CD57+ cells the subpopulation of T-cells most closely corresponding to the concept of senescent cells.

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“…In our study, the morphology of the cells is in accordance with the type 1 stem cell fibroblast-like progenitor cells previously described by Mets et al . (23) and the fibroblastoid cell sub-classifications of BM-hMSCs previously outlined by Montesinos et al . (24) (i.e., lamellipodia-lamellipodia, lamellipodia-filopodia, filopodia-filopodia and triangular).…”

Section: Resultsmentioning

confidence: 99%

Genetic stability of bone marrow-derived human mesenchymal stromal cells in the Quantum System

et al. 2013

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Background aims The Quantum® Cell Expansion System (Quantum; Terumo BCT, Inc, Lakewood, CO, USA) is a novel hollow fiber-based device that automates and closes the cell culture process, reducing labor intensive tasks such as manual cell culture feeding and harvesting. The manual cell selection and expansion processes for the production of clinical-scale quantities of bone marrow-derived human mesenchymal stromal cells (BM-hMSCs) have been successfully translated onto the Quantum platform previously. The formerly static, manual, in vitro process performed primarily on tissue culture polystyrene substrates may raise the question of whether BM-hMSCs cultured on a hollow fiber platform yields comparable cell quality. Methods A rigorous battery of assays was used to determine the genetic stability of BM-hMSCs selected and produced with the Quantum. In this study, genetic stability was determined by assessing spectral karyotype, micronucleus formation and tumorigenicity to resolve chromosomal aberrations in the stem cell population. Cell phenotype, adherent growth kinetics and tri-lineage differentiation were also evaluated. HMSC bone marrow aspirates, obtained from three approved donors, were expanded in parallel using T225 culture flasks and the Quantum. Results BM-hMSCs harvested from the Quantum demonstrated immunophenotype, morphology and tri-lineage differentiation capacity characteristics consistent with the International Society of Cell Therapy standard for hMSCs. Cell populations showed no malignant neoplastic formation in athymic mice 60 days post-transplant, no clonal chromosomal aberrations were observed and no DNA damage was found as measured by micronucleus formation. Conclusions Quantum-produced BM-hMSCs are of comparable quality and demonstrate analogous genetic stability to BM-hMSCs cultured on tissue culture polystyrene substrates.

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Variations in the stromal cell population of human bone marrow during aging

Cited by 47 publications

References 27 publications

Enumeration of the colony-forming units–fibroblast from mouse and human bone marrow in normal and pathological conditions

Enumeration of the colony-forming units–fibroblast from mouse and human bone marrow in normal and pathological conditions

Cellular aging and senescence characteristics of human T-lymphocytes

Genetic stability of bone marrow-derived human mesenchymal stromal cells in the Quantum System

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