Aging is associated with decreased maximal life span and accelerated senescence of bone marrow stromal cells,

Stenderup, Karin; Justesen, Jeannette; Clausen, Christian; Kassem, Moustapha

doi:10.1016/j.bone.2003.07.005

Cited by 1,031 publications

(825 citation statements)

References 48 publications

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“…Bone marrow‐derived mesenchymal stem cells tend to partially lose their self‐renewal capacity and differentiate into adipocytes instead of osteocytes with aging, which causes bone loss and fat accumulation (Moerman, Teng, Lipschitz, & Lecka‐Czernik, 2004). These changes include impaired capacity of proliferation, imbalanced differentiation and increased senescence (Sethe, Scutt, & Stolzing, 2006; Stenderup, Justesen, Clausen, & Kassem, 2003). Our findings showed that aged BMMSCs had decreased osteogenesis, elevated adipogenesis and decreased proliferation compared with young BMMSCs; these results are in line with the previous findings.…”

Section: Discussionmentioning

confidence: 99%

Autophagy controls mesenchymal stem cell properties and senescence during bone aging

et al. 2017

Aging Cell

261

194

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SummaryBone marrow‐derived mesenchymal stem cells (BMMSCs) exhibit degenerative changes, including imbalanced differentiation and reduced proliferation during aging, that contribute to age‐related bone loss. We demonstrate here that autophagy is significantly reduced in aged BMMSCs compared with young BMMSCs. The autophagy inhibitor 3‐methyladenine (3‐MA) could turn young BMMSCs into a relatively aged state by reducing their osteogenic differentiation and proliferation capacity and enhancing their adipogenic differentiation capacity. Accordingly, the autophagy activator rapamycin could restore the biological properties of aged BMMSCs by increasing osteogenic differentiation and proliferation capacity and decreasing adipogenic differentiation capacity. Possible underlying mechanisms were explored, and the analysis revealed that autophagy could affect reactive oxygen species and p53 levels, thus regulating biological properties of BMMSCs. In an in vivo study, we found that activation of autophagy restored bone loss in aged mice. In conclusion, our results suggest that autophagy plays a pivotal role in the aging of BMMSCs, and activation of autophagy could partially reverse this aging and may represent a potential therapeutic avenue to clinically treat age‐related bone loss.

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Section: Discussionmentioning

confidence: 99%

Autophagy controls mesenchymal stem cell properties and senescence during bone aging

et al. 2017

Aging Cell

261

194

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“…In 1961, Hayflick and Moorhead discovered that in vitro, human skin fibroblasts undergo only a limited number of population doublings (termed Hayflick limit), and that this number decreased with increasing donor age (Hayflick and Moorhead, 1961). Similar to other human diploid cells, MSC exhibit replicative senescence in vitro, as demonstrated by a number of investigators (Fehrer et al, 2007;Kern et al, 2006;Stenderup et al, 2003;Stenderup et al, 2004;Stolzing et al, 2008). The in vitro senescent phenotype includes the following characteristic features: (i) irreversible arrest of cell division (in contrast to quiescence, where this lock is reversible), (ii) resistance to apoptotic death, and (iii) the excretion of molecules normally secreted during wound repair and infection, such as inflammatory cytokines, proteases and growth factors, the latter having detrimental consequences for the surrounding tissue (Campisi, 2001).…”

Section: Msc In Vitro Senescencementioning

confidence: 99%

“…The in vitro senescent phenotype includes the following characteristic features: (i) irreversible arrest of cell division (in contrast to quiescence, where this lock is reversible), (ii) resistance to apoptotic death, and (iii) the excretion of molecules normally secreted during wound repair and infection, such as inflammatory cytokines, proteases and growth factors, the latter having detrimental consequences for the surrounding tissue (Campisi, 2001). Some, but not all of these characteristics have also been described for MSC cultures (Fehrer et al, 2007;Kern et al, 2006;Stenderup et al, 2003;Stenderup et al, 2004;Stolzing et al, 2008)…”

Section: Msc In Vitro Senescencementioning

confidence: 99%

Controversial issue: Is it safe to employ mesenchymal stem cells in cell-based therapies?

Lepperdinger

Brunauer

Jamnig

et al. 2008

Experimental Gerontology

116

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“…Rabbit tendon injuries repaired with autologous MSCs from young or aged animals produced repair tissue with equivalent material properties [16]. The literature is conflicting whether osteogenic and adipogenic MSC differentiation is agedependent, with some studies suggesting it is independent of age [42,46,49] and others dependent on age [14,30]. For human MSC chondrogenesis, both age-dependent and age-independent findings have also been noted [37,41,43].…”

Section: Introductionmentioning

confidence: 99%

Cartilage Matrix Formation by Bovine Mesenchymal Stem Cells in Three-dimensional Culture Is Age-dependent

Erickson

Veen

Sengupta

et al. 2011

Clinical Orthopaedics &Amp; Related Research

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Background Cartilage degeneration is common in the aged, and aged chondrocytes are inferior to juvenile chondrocytes in producing cartilage-specific extracellular matrix. Mesenchymal stem cells (MSCs) are an alternative cell type that can differentiate toward the chondrocyte phenotype. Aging may influence MSC chondrogenesis but remains less well studied, particularly in the bovine system. Questions/purposes The objectives of this study were (1) to confirm age-related changes in bovine articular cartilage, establish how age affects chondrogenesis in cultured pellets for (2) chondrocytes and (3) MSCs, and (4) determine age-related changes in the biochemical and biomechanical development of clinically relevant MSC-seeded hydrogels. Methods Native bovine articular cartilage from fetal (n = 3 donors), juvenile (n = 3 donors), and adult (n = 3 donors) animals was analyzed for mechanical and biochemical properties (n = 3-5 per donor). Chondrocyte and MSC pellets (n = 3 donors per age) were cultured for 6 weeks before analysis of biochemical content (n = 3 per donor). Bone marrow-derived MSCs of each age were also cultured within hyaluronic acid hydrogels for 3 weeks and analyzed for matrix deposition and mechanical properties (n = 4 per age). Results Articular cartilage mechanical properties and collagen content increased with age. We observed robust matrix accumulation in three-dimensional pellet culture by fetal chondrocytes with diminished collagen-forming capacity in adult chondrocytes. Chondrogenic induction of MSCs was greater in fetal and juvenile cell pellets. Likewise, fetal and juvenile MSCs in hydrogels imparted greater matrix and mechanical properties. Conclusions Donor age and biochemical microenvironment were major determinants of both bovine chondrocyte and MSC functional capacity. Clinical Relevance In vitro model systems should be evaluated in the context of age-related changes and should be benchmarked against human MSC data.

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Aging is associated with decreased maximal life span and accelerated senescence of bone marrow stromal cells,

Cited by 1,031 publications

References 48 publications

Autophagy controls mesenchymal stem cell properties and senescence during bone aging

Autophagy controls mesenchymal stem cell properties and senescence during bone aging

Controversial issue: Is it safe to employ mesenchymal stem cells in cell-based therapies?

Cartilage Matrix Formation by Bovine Mesenchymal Stem Cells in Three-dimensional Culture Is Age-dependent

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