Dedifferentiated adult articular chondrocytes: a population of human multipotent primitive cells

Fuente, Ricardo de la; Abad, José Luís; García‐Castro, Javier; Fernández-Miguel, Gemma; Pétriz, Jordi; Rubio, Daniel; Vicario‐Abejón, Carlos; Guillén, Pedro; González, Manuel A.; Bernad, António

doi:10.1016/j.yexcr.2004.02.026

Cited by 75 publications

(52 citation statements)

References 60 publications

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“…These Wndings are consistent with previous reports (de la Fuente et al 2004;Oswald et al 2004) and the morphological characteristics observed here correspond to those generally displayed by mesenchymal stromal (stem) cells. In this context, Leong et al (2006) assumed the existence of two diVerent cell types and thereby postulated a heterogeneous ASC population.…”

Section: Discussionsupporting

confidence: 94%

Neurogenic transdifferentiation of human adipose-derived stem cells? A critical protocol reevaluation with special emphasis on cell proliferation and cell cycle alterations

Kompisch

Lange

Steinemann

et al. 2010

Histochem Cell Biol

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Adipose-derived stem cells (ASCs) are reported to display multilineage differentiation potential, including neuroectodermal pathways. The aim of the present study was to critically re-evaluate the potential neurogenic (trans-)differentiation capacity of ASCs using a neurogenic induction protocol based on the combination of isobutylmethylxanthine (IBMX), indomethacin and insulin. ASCs isolated from lipo-aspirate samples of five healthy female donors were characterized and potential neurogenic (trans-)differentiation was assessed by means of immunohistochemistry and gene expression analyses. Cell proliferation and cell cycle alterations were studied, and the expression of CREB/ATF transcription factors was analyzed. ASCs expressed CD59, CD90 and CD105, and were tested negative for CD34 and CD45. Under neurogenic induction, ASCs adopted a characteristic morphology comparable to neur(on)al progenitors and expressed musashi1, β-III-tubulin and nestin. Gene expression analyses revealed an increased expression of β-III-tubulin, GFAP, vimentin and BDNF, as well as SOX4 in induced ASCs. Cell proliferation was significantly reduced under neurogenic induction; cell cycle analyses showed a G2-cell cycle arrest accompanied by differential expression of key regulators of cell cycle progression. Differential expression of CREB/ATF transcription factors could be observed on neurogenic induction, pointing to a decisive role of the cAMP-CREB/ATF system. Our findings may point to a potential neurogenic (trans-)differentiation of ASCs into early neur(on)al progenitors, but do not present definite evidence for it. Especially, the adoption of a neural progenitor cell-like morphology must not automatically be misinterpreted as a specific characteristic of a respective (trans-)differentiation process, as this may as well be caused by alterations of cell cycle progression.

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Section: Discussionsupporting

confidence: 94%

Neurogenic transdifferentiation of human adipose-derived stem cells? A critical protocol reevaluation with special emphasis on cell proliferation and cell cycle alterations

Kompisch

Lange

Steinemann

et al. 2010

Histochem Cell Biol

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“…Migram [4] described that these osteoblasts and osteoclasts are probably derived from the synovial membrane as free cells in synovial spaces, and there may be a similar origin of metaplastic fat cells. On the other hand, some experimental studies [20,21] have shown the lipogenetic differentiation in cell cultures of human articular cartilage and have indicated the presence of mesenchymal progenitor cells in articular cartilage [20] or a multipotent population of dedifferentiated articular chondrocytes themselves [21]. In our study, all ILBs with extramedullary lipometaplasia possessed detached articular cartilage.…”

Section: Resultssupporting

confidence: 43%

Fatty lesions in intra-articular loose bodies: a histopathological study of non-primary synovial chondromatosis cases

et al. 2011

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Intra-articular loose bodies (ILBs) are not uncommon conditions in patients with various joint diseases. Their morphological alterations have been investigated in detail, but little attention has been paid to their fatty lesions. In this study, we examined fatty bone marrow, fat cells without bone marrow structures (extramedullary fat cells), and their necrotic changes in 55 ILBs surgically removed from 42 patients, excluding primary synovial chondromatosis cases. The presence of viable re-vascularized vessels with or without enchondral ossification could discriminate 19 re-attached ILBs from 36 true free ILBs. Fatty bone marrow was found in 25 ILBs, and its necrosis was recognized in 11 (44.0%) of them. Extramedullary fat cells, characterized by single or clustered fat cells focally or multifocally distributed in fibrous or cartilaginous stroma, were identified in seven true free ILBs (7of 55, 12.7%), and all of them were focally necrotic. Unique lipomembranous changes were detected in 7 (12.7%) of 55 ILBs; they were found in 4 (36.4%) of 11 ILBs of necrotic bone marrow and were associated with 3 (42.9%) of 7 necrotic extramedullary fatty lesions. These changes were highlighted by periodic-acid Schiff and Masson's trichrome stain more clearly. We concluded that extramedullary fat cells represent lipometaplasia in ILBs with no blood supply. We considered that lipomembranous changes in ILBs can be a useful hallmark for necrotic bone marrow or necrosis of extramedullary lipometaplastic lesions.

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“…This behavior could be probably explained by the culture medium components like basic FGF (Battula et al 2007) or it could be due to the in vitro microenvironment that changes the typical niche behavior of these cells and makes them regress to a more embryonic unspecialized form. In fact, as in other cell populations, it occurs that BM-MSCs dedifferentiate in a progenitor cell subpopulation, which renders these cells sensitive to their microenvironment for subsequent differentiation (Barbero et al 2003;De la Fuente et al 2004). In our experiments, Oct-4 appeared in the cell cytoplasm and weakly in the nuclear compartment as demonstrated in literature (Miki and Strom 2006).…”

Section: Discussionmentioning

confidence: 99%

Comparison of equine bone marrow-, umbilical cord matrix and amniotic fluid-derived progenitor cells

et al. 2010

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The aim of the study was to compare in vitro the stemness features of horse progenitor cells derived from bone marrow (BM-MSCs), amniotic fluid (AF-MSCs) and umbilical cord matrix (EUC-MSCs). It has been suggested that there may be a stem cell population within both umbilical cord matrix and amniotic fluid. However, little knowledge exists about the characteristics of these progenitor cells within these sources in the equine species. This study wanted to investigate an alternative and non-invasive stem cell source for the equine tissue engineering and to learn more about the properties of these cells for future cell banking. Bone marrow, umbilical cord and amniotic fluid samples were harvested from different horses. Cells were analyzed for proliferation, immunocytochemical, stem cell gene expression and multilineage plasticity. BM- and AF-MSCs took similar time to reach confluence and showed comparable plating efficiency. All cell lines expressed identical stem cell markers and capability to differentiate towards osteogenic lineage. Almost all cell lines differentiated into the adipogenic lineage as demonstrated by cytochemical staining, even if no adipose gene expression was detectable for AF-MSCs. AF- and EUC-MSCs showed a limited chondrogenic differentiation compared with BM-MSCs as demonstrated by histological and biochemical analyses. These findings suggest that AF-MSCs appeared to be a readily obtainable and highly proliferative cell line from an uninvasive source that may represent a good model system for stem cell biology. More studies are needed to investigate their multilineage potential. EUC-MSCs need to be further investigated regarding their particular behavior in vitro represented by spheroid formation.

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Dedifferentiated adult articular chondrocytes: a population of human multipotent primitive cells

Cited by 75 publications

References 60 publications

Neurogenic transdifferentiation of human adipose-derived stem cells? A critical protocol reevaluation with special emphasis on cell proliferation and cell cycle alterations

Neurogenic transdifferentiation of human adipose-derived stem cells? A critical protocol reevaluation with special emphasis on cell proliferation and cell cycle alterations

Fatty lesions in intra-articular loose bodies: a histopathological study of non-primary synovial chondromatosis cases

Comparison of equine bone marrow-, umbilical cord matrix and amniotic fluid-derived progenitor cells

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