Age-related changes in human bone marrow-derived mesenchymal stem cells: Consequences for cell therapies

Stolzing, Alexandra; Jones, Elena; McGonagle, Dennis; Scutt, Andrew

doi:10.1016/j.mad.2007.12.002

Cited by 1,044 publications

(881 citation statements)

References 56 publications

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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%

See 1 more Smart Citation

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

Lepperdinger

Brunauer

Jamnig

et al. 2008

Experimental Gerontology

117

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Section: Msc In Vitro Senescencementioning

confidence: 99%

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

117

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“…However, these populations do not develop to sizable proportions under normal culture conditions and their isolation and expansion require enriched substrates and culture media. In spite of their presumed existence in vivo, accumulating evidence indicates that ageing decreases the frequency, growth, and differentiation potential of adult SC [18][19][20][21][22].…”

Section: Introductionmentioning

confidence: 99%

The Lamina Propria of Adult Human Oral Mucosa Harbors a Novel Stem Cell Population

et al. 2010

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The highly regenerative capacity of the human adult oral mucosa suggests the existence of a robust stem cell (SC) population in its lamina propria (OMLP). The purpose of this study was to characterize the availability, growth, immunophenotype, and potency of this presumable SC population. Cells positive for the embryonic stem cell transcription factors Oct4 and Sox2 and for p75 formed distinct cord-like structure in the OMLP. Regardless of donor age, trillions of cells, termed human oral mucosa stem cells (hOMSC), 95% of which express mesenchymal stromal cell markers, were simply, and reproducibly produced from a biopsy of 3-4 3 2 3 1 mm 3 . A total of 40-60% of these cells was positive for Oct4, Sox2, and Nanog and 60-80% expressed constitutively neural and neural crest SC markers. hOMSC differentiated in culture into mesodermal (osteoblastic, chondroblastic, and adipocytic), definitive endoderm and ectodermal (neuronal) lineages. Unexpectedly, hOMSC treated with dexamethasone formed tumors consisting of two germ layer-derived tissues when transplanted in severe combined immune deficiency mice. The tumors consisted of tissues produced by neural crest cells during embryogenesis-cartilage, bone, fat, striated muscle, and neural tissue. These results show that the adult OMLP harbors a primitive SC population with a distinct primitive neural-crest like phenotype and identifies the in vivo localization of putative ancestors for this population. This is the first report on ectodermal-and mesodermal-derived mixed tumors formation by a SC population derived from a nonmalignant somatic adult human tissue. STEM CELLS 2010;28:984-995 Disclosure of potential conflicts of interest is found at the end of this article.

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“…MSCs are a multipotent cell type found in bone marrow that can differentiate along osteogenic, chondrogenic, and adipogenic lineages [4]. Like chondrocytes, however, MSC properties also change with age; MSC density in bone marrow decreases and aged MSCs are slower to proliferate [47]. Regardless, aged MSCs can produce functional repair tissue.…”

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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Age-related changes in human bone marrow-derived mesenchymal stem cells: Consequences for cell therapies

Cited by 1,044 publications

References 56 publications

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

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

The Lamina Propria of Adult Human Oral Mucosa Harbors a Novel Stem Cell Population

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

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