Neither Notch1 Expression nor Cellular Size Correlate with Mesenchymal Stem Cell Properties of Adult Articular Chondrocytes

Karlsson, Camilla; Stenhamre, Hanna; Sandstedt, Joakim; Lindahl, Anders

doi:10.1159/000113409

Cited by 24 publications

(24 citation statements)

References 48 publications

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“…Our results as well as previously published data demonstrate that Notch1 is exclusively localized on cells in the superficial zone of the articular cartilage in adult bovines and humans (Dowthwaite et al. 2004; Karlsson et al. 2007, 2008).…”

Section: Discussionsupporting

confidence: 91%

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Identification of a stem cell niche in the zone of Ranvier within the knee joint

Karlsson¹,

Thornemo²,

Henriksson

et al. 2009

Journal of Anatomy

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113

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A superficial lesion of the articular cartilage does not spontaneously self-repair and has been suggested to be partly due to lack of progenitor cells within the joint that can reach the site of injury. To study whether progenitor cells are present within the joint, 3-month-old New Zealand white rabbits were exposed to bromodeoxyuridine (BrdU) for 12 consecutive days and were then sacrificed 4, 6, 10, 14, 28 and 56 days after the first BrdU administration. Presence of BrdU and localization of progenitor markers were detected using immunohistochemistry. After 10 days of BrdU exposure, BrdU-positive cells, i.e. proliferating cells, were abundantly detected in the epiphyseal plate, the perichondrial groove of Ranvier, and in all zones of the articular cartilage. After a wash-out period, BrdUpositive cells were still present, i.e. those considered to be progenitor cells, in these regions of the knee except for the proliferative zone of the epiphyseal plate. Cells in the perichondrial groove of Ranvier were further positive for several markers associated with progenitor cells and stem cell niches, including Stro-1, Jagged1, and BMPr1a. Our results demonstrate that a small population of progenitor cells is present in the perichondrial groove of Ranvier as well as within the articular cartilage in the knee. The perichondrial groove of Ranvier also demonstrates the properties of a stem cell niche.

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Section: Discussionsupporting

confidence: 91%

“…These discrepancies might be explained by the different developmental stage of the animals used in the different studies. We have demonstrated earlier that Notch1 is not a marker for a population of chondrogenic progenitor cells in adult bovines (Karlsson et al. 2008).…”

Section: Discussionmentioning

confidence: 89%

Identification of a stem cell niche in the zone of Ranvier within the knee joint

Karlsson¹,

Thornemo²,

Henriksson

et al. 2009

Journal of Anatomy

Self Cite

113

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“…3A and B). These cells also expressed Notch homology 1 (Notch1), which has been suggested as a marker for chondrogenic progenitor cells [27,28]. DPC NP were negative for CD90 and CD271, whereas DPC AF were negative for CD106, CD29 and hypoxic (3.5% O 2 ) conditions.…”

Section: Cd146 Expressed On Dpc Npmentioning

confidence: 99%

Coupling of small leucine-rich proteoglycans to hypoxic survival of a progenitor cell-like subpopulation in Rhesus Macaque intervertebral disc

et al. 2013

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Degeneration of the intervertebral disc (IVD) is a major spinal disorder that associates with neck and back pain. Recent studies of clinical samples and animal models for IVD degeneration have identified cells with multi-potency in the IVD. However, IVD tissue-specific progenitor cells and their niche components are not clear, although degenerated IVD-derived cells possess in vitro characteristics of mesenchymal stromal cell (MSCs). Here, we firstly identified the tissue-specific intervertebral disc progenitor cells (DPCs) from healthy Rhesus monkey and report the niche components modulated the survival of DPCs under hypoxia. DPCs possess clonogenicity, multipotency and retain differentiation potential after extended expansion in vitro and in vivo. In particular, the nucleus pulposus-derived DPCs are sensitive to low oxygen tension and undergo apoptosis under hypoxic conditions due to their inability to induce/stabilize hypoxia-inducible factors (HIF). The presence of small leucine-rich proteoglycans (SLRP), biglycan or decorin, can reduce the susceptibility of DPCs to hypoxia-induced apoptosis via promoting the activation/stabilization of HIF-1α and HIF-2α. As IVD is avascular, we propose SLRPs are niche components of DPCs in IVD homeostasis, providing new insights in progenitor cell biology and niche factors under a hypoxic microenvironment.

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“…Compared with numerous reports on classic sources such as bone marrow, there is only limited information about the presence of MPCs with defined biomarkers in human articular cartilage [2-5,9]. Despite extensive efforts, the emerging field of stem cell research still strives to establish well-defined marker constellations, which unambiguously describe the typical stem/progenitor cell phenotype.…”

Section: Introductionmentioning

confidence: 99%

Relative percentage and zonal distribution of mesenchymal progenitor cells in human osteoarthritic and normal cartilage

et al. 2011

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IntroductionMesenchymal stem cells (MSC) are highly attractive for use in cartilage regeneration. To date, MSC are usually recruited from subchondral bone marrow using microfracture. Recent data suggest that isolated cells from adult human articular cartilage, which express the combination of the cell-surface markers CD105 and CD166, are multi-potent mesenchymal progenitor cells (MPC) with characteristics similar to MSC. MPC within the cartilage matrix, the target of tissue regeneration, may provide the basis for in situ regeneration of focal cartilage defects. However, there is only limited information concerning the presence/abundance of CD105+/CD166+ MPC in human articular cartilage. The present study therefore assessed the relative percentage and particularly the zonal distribution of cartilage MPC using the markers CD105/CD166.MethodsSpecimens of human osteoarthritic (OA; n = 11) and normal (n = 3) cartilage were used for either cell isolation or immunohistochemistry. Due to low numbers, isolated cells were expanded for 2 weeks and then analyzed by flow cytometry (FACS) or immunofluorescence in chamber slides for the expression of CD105 and CD166. Following immunomagnetic separation of CD166+/- OA cells, multi-lineage differentiation assays were performed. Also, the zonal distribution of CD166+ cells within the matrix of OA and normal cartilage was analyzed by immunohistochemistry.ResultsFACS analysis showed that 16.7 ± 2.1% (mean ± SEM) of OA and 15.3 ± 2.3 of normal chondrocytes (n.s.) were CD105+/CD166+ and thus carried the established MPC marker combination. Similarly, 13.2% ± 0.9% and 11.7 ± 2.1 of CD105+/CD166+cells, respectively, were identified by immunofluorescence in adherent OA and normal chondrocytes. The CD166+ enriched OA cells showed a stronger induction of the chondrogenic phenotype in differentiation assays than the CD166+ depleted cell population, underlining the chondrogenic potential of the MPC. Strikingly, CD166+ cells in OA and normal articular cartilage sections (22.1 ± 1.7% and 23.6% ± 1.4%, respectively; n.s.) were almost exclusively located in the superficial and middle zone.ConclusionsThe present results underline the suitability of CD166 as a biomarker to identify and, in particular, localize and/or enrich resident MPC with a high chondrogenic potential in human articular cartilage. The percentage of MPC in both OA and normal cartilage is substantially higher than previously reported, suggesting a yet unexplored reserve capacity for regeneration.

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Neither Notch1 Expression nor Cellular Size Correlate with Mesenchymal Stem Cell Properties of Adult Articular Chondrocytes

Cited by 24 publications

References 48 publications

Identification of a stem cell niche in the zone of Ranvier within the knee joint

Identification of a stem cell niche in the zone of Ranvier within the knee joint

Coupling of small leucine-rich proteoglycans to hypoxic survival of a progenitor cell-like subpopulation in Rhesus Macaque intervertebral disc

Relative percentage and zonal distribution of mesenchymal progenitor cells in human osteoarthritic and normal cartilage

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