A predominant Th1 polarization is present in synovial fluid of end-stage osteoarthritic knee joints: analysis of peripheral blood, synovial fluid and synovial membrane.

Thorough understanding of the complex pathophysiology of osteoarthritis (OA) is necessary in order to open new avenues for treatment. The aim of this study was to characterize the CD4+ T cell population and evaluate their activation and polarization status in OA joints. Fifty-five patients with end-stage knee OA (Kellgren-Lawrence grades III-IV) who underwent surgery for total knee arthroplasty (TKA) were enrolled into this study. Matched samples of synovial membrane (SM), synovial fluid (SF) and peripheral blood (PB) were analysed for CD3+ CD4+ CD8- T cell subsets [T helper type 1 (Th1), Th2, Th17, regulatory T cells] and activation status (CD25, CD69, CD45RO, CD45RA, CD62L) by flow cytometry. Subset-specific cytokines were analysed by cytometric bead array (CBA). SM and SF samples showed a distinct infiltration pattern of CD4+ T cells. In comparison to PB, a higher amount of joint-derived T cells was polarized into CD3+ CD4+ CD8- T cell subsets, with the most significant increase for proinflammatory Th1 cells in SF. CBA analysis revealed significantly increased immunomodulating cytokines [interferon (IFN)-γ, interleukin (IL)-2 and IL-10] in SF compared to PB. Whereas in PB only a small proportion of CD4+ T cells were activated, the majority of joint-derived CD4+ T cells can be characterized as activated effector memory cells (CD69+ CD45RO+ CD62L- ). End-stage OA knees are characterized by an increased CD4+ T cell polarization towards activated Th1 cells and cytokine secretion compared to PB. This local inflammation may contribute to disease aggravation and eventually perpetuate the disease process.

[Inflammation and osteoarthritis-related pain]. / Die Rolle der Inflammation bei Arthroseschmerzen.

Osteoarthritis (OA) is one of the major causes of chronic pain. Although OA has long been considered a non-inflammatory "wear and tear" disease leading to loss of articular cartilage, recent findings provide convincing evidence that inflammatory mechanisms play a pivotal role in the pathophysiology of OA. In OA mononuclear cells (e. g. T­cells and macrophages) infiltrate the synovial membrane and the levels of pro-inflammatory cytokines in peripheral blood and synovial fluid samples are elevated. Increased release of inflammatory mediators including interleukin (IL) IL-1ß, IL-6, IL-8, IL-15 und tumor necrosis factor alpha (TNF­α) induces the expression of proteolytic enzymes such as matrix metalloproteinases resulting in cartilage breakdown. Molecular and cellular interactions between the immune and nervous system are also involved in the development of OA-related pain. Inflammatory mediators including IL-6 und TNF­α lead to peripheral sensitization of joint nociceptors and growth factors (e. g. NGF) trigger the expression of TRPV1 channels in primary afferents. Moreover, neuropeptides reduce the threshold of nociceptors of OA joints. The current review highlights the role of inflammatory mechanisms in OA-induced joint pain considering clinical signs of inflammation and major inflammatory pathways.

Unicompartmental and bicompartmental knee osteoarthritis show different patterns of mononuclear cell infiltration and cytokine release in the affected joints.

It is still controversial which cell types are responsible for synovial inflammation in osteoarthritic (OA) joints. The aim of this study was to quantify the mononuclear cell populations and their cytokines in patients with different knee OA subtypes. Synovial membrane (SM), synovial fluid (SF) and peripheral blood (PB) were harvested from patients with unicompartmental (UC) and bicompartmental (BC) knee OA. Frequencies of mononuclear cells were assessed by flow cytometry in PB and SM. Naive SF samples were analysed for a broad variety of cytokines by multiplex analysis. SM of both groups displayed a distinct mononuclear cell infiltration, with CD14(+) macrophages being the major cell population, followed by CD4(+) T cells and only small numbers of CD8(+) T, CD19(+) B and CD16(+) CD56(+) natural killer (NK) cells. Between the two groups, SM of BC OA showed significantly higher amounts of mononuclear cells (135·7 ± 180 versus 805 ± 675 cells/mg, P = 0·0009) and higher CD4(+) T cell presence (3·4 ± 4·6 versus 9·1 ± 7·5%, P = 0·0267). SF of BC OA displayed significantly higher concentrations for a number of proinflammatory cytokines [CXCL1, eotaxin, interferon (IFN)-γ, interleukin (IL)-7, IL-8, IL-9, IL-12]. UC and BC OA show significant differences in their synovial inflammatory pattern. Whereas in UC OA CD14(+) macrophages are the predominant cell population, BC OA has a higher inflammatory profile and seems to be driven by CD14(+) macrophages and CD4(+) T cells. Inclusion of clinical information into the analysis of cellular and molecular results is pivotal in understanding the pathophysiology of OA.

Preoperative scoring and limits of prognostication: functional outcome after surgical decompression in metastatic spinal cord compression.

OBJECTIVE: To determine whether preoperative parameters correlate with the postoperative functional outcome in para- and tetraplegic patients with lung, kidney, breast and prostate cancer and metastatic spinal cord compression (MSCC). METHODS: Information on 43 patients undergoing decompressive surgery and rehabilitation for MSCC was reviewed, including primary tumor, age, pre- and postoperative ambulation status, mobility subcategory of the Spinal Cord Injury Measure (mSCIM) and the Tokuhashi score. Differences between groups were analyzed by the nonparametric χ(2) test, and correlation coefficients (Spearman's rho) were computed. RESULTS: Preoperative ambulation (p < 0.001), the American Spinal Injury Association Impairment Scale (p < 0.001) and the type of operation (p = 0.02) influenced the postoperative functional outcome. Any positive change in the mSCIM was influenced by preoperative ambulation (p < 0.001). Patients with breast carcinoma showed significantly more positive changes in the mSCIM compared with other tumors (p = 0.002). No correlation was found between the treatment categories of the Tokuhashi score and the preoperative ambulatory status (p = 0.13) or the change in ambulation status (p = 0.29). CONCLUSION: The postoperative functional outcome of MSCC patients shows a linear association between the categories of the Tokuhashi score and the change in ambulation status. We recommend surgical decompression even in a palliative situation (Tokuhashi score 0-8) with the aim of optimizing the short-term rehabilitation outcome.

The influence of bone marrow- and synovium-derived mesenchymal stromal cells from osteoarthritis patients on regulatory T cells in co-culture.

There is increasing evidence that inflammation in the synovium plays a major role in the progression of osteoarthritis (OA). However, the immunogenic properties of mesenchymal stromal cells (MSCs), which are considered to regulate immunity in various diseases, remain largely unknown in OA. The purpose of this study was to determine the influence of MSCs from OA patients on regulatory T cells (Tregs ) in an allogeneic co-culture model. Bone marrow (BM) and synovial membrane (SM) were harvested from hip joints of OA patients and co-cultured with lymphocytes enriched in CD4(+) CD25(+) CD127(-) regulatory T cells (Treg (+) LC) from healthy donors. Treg proportions and MSC markers were assessed by flow cytometry. Cytokine levels were assessed after 2 and 5 days of co-cultivation. Additionally, Treg (+) LC cultures were analysed in the presence of interleukin (IL)-6 and MSC-supernatant complemented medium. B-MSCs and S-MSCs were able to retain the Treg proportion compared to lymphocyte monocultures. T cell-MSC co-cultures showed a significant increase of IL-6 compared to MSC cultures. S-MSCs produced higher amounts of IL-6 compared to B-MSCs, both in single and T cell co-cultures. The effect of retaining the Treg percentage could be reproduced partially by IL-6 addition to the medium, but could only be observed fully when using MSC culture supernatants. Our data demonstrate that retaining the Treg phenotype in MSC-T cell co-cultures can be mediated by MSC derived from OA patients. IL-6 plays an important role in mediating these processes. To our knowledge, this study is the first describing the interaction of MSCs from OA patients and Tregs in an allogeneic co-culture model.

HLA-DRB and HLA-DQA/HLA-DQB allele and haplotype frequencies in Iranian patients with aggressive periodontitis.

BACKGROUND AND OBJECTIVE: Genetic backgrounds play a key role in susceptibility to and protection against a spectrum of periodontal diseases. Like other infectious diseases, the human leukocyte antigen (HLA) have been found to be associated with periodontitis. This study aimed to investigate differences in allele and haplotype frequencies of HLA class II antigens in a sample of Iranian patients with aggressive periodontitis compared with a healthy control group. MATERIAL AND METHODS: Fifty unrelated patients with aggressive periodontitis and 130 healthy volunteers were enrolled in this study. HLA genotyping for HLA-DRB, HLA-DQA1 and HLA-DQB1 was performed using the PCR with sequence-specific primers. Allele and haplotype frequencies were compared across groups. RESULTS: The frequencies of HLA-DQA1*03:01, HLA-DQB1*03:02 and HLA-DQB1*03:05 alleles, as well as that of the HLA-DRB1*04:01 allele, were significantly higher in patients with aggressive periodontitis compared with control subjects (p = 0.01, p = 0.04, p = 0.05 and p = 0.04, respectively). In contrast, the frequency of the HLA-DQB1*0603 allele was significantly lower in patients with aggressive periodontitis compared with control subjects (p = 0.006; odds ratio = 0.20). With regard to haplotype association, a significantly higher frequency of two haplotypes - HLA-DRB1*04:01/HLA-DQA1*03:01/HLA-DQB1*03:02 and HLA-DRB1*16:01/HLA-DQA1*01:03/HLA-DQB1*05:01 - was observed in patients with aggressive periodontitis compared with healthy controls (p = 0.01, odds ratio = 2.56 and p = 0.05, odds ratio = 5.38, respectively). CONCLUSION: These results provide additional evidence that class II HLA polymorphisms, particularly in the DQ locus, are associated with protection against and susceptibility to aggressive periodontitis.

Single-nucleotide polymorphisms of TNFA and IL1 in allergic rhinitis.

BACKGROUND: Allergic rhinitis is a complex polygenic disorder of the upper respiratory tract. Given that proinflammatory cytokines such as tumor necrosis factor (TNF) and interleukin (IL) 1 seem to play a role in the development of allergic rhinitis, we evaluated the associations between various single-nucleotide polymorphisms (SNPs) of the TNF and IL1 genes in a case-control study. METHODS: The study population comprised 98 patients with allergic rhinitis. Genotyping was performed using polymerase chain reaction with sequence-specific primers for 2 TNFA promoter variants (rs1800629 and rs361525), 1 variant in the promoter region of IL1A (rs1800587), 2 SNPs in the IL1B gene (rs16944 and rs1 143634), 1 variant in the IL1 receptor (rs2234650), and 1 in IL1RA (rs315952). RESULTS: Patients who were homozygous for the T allele of rs16944 in IL1B had an 8.1-fold greater risk of allergic rhinitis than those with the C allele. In TNFA, a significant relationship was also detected between rs1800629 and rs361525 and allergic rhinitis. Except for rs1800587 in IL1A and rs315952 in IL1RA, significant differences were found between the patient and control groups for all other SNPs. CONCLUSIONS: We found that allelic variants in the TNFA and IL1 genes were not only associated with the risk of developing allergic rhinitis, but also affected disease course and severity.

[In vitro analysis of the impact of metal ions on human lymphocyte cultures]. / In-vitro-Analyse des Einflusses von Metallionen auf humane Lymphozyten.

The use of metal implants has become increasingly more frequent in all fields of medicine throughout the past decades. Numerous studies have demonstrated that metal ions released from these implants can be detected in body fluids remote from the implants. Although diseases directly linked to the release of these ions seem to be rare, the general public is unsettled. In this study we aimed to analyze the impact of molybdenum(V), cobalt(II), chromium(III) and nickel(II) ions on cell surface markers (CD25, CD38, CD69, CD95) and viability (7-AAD/AnnexinV) of human CD4+ T-lymphocytes in vitro. Cobalt(II) ions at a concentration of 1000 µg/l led to a significant suppression of lymphocyte activation markers while nickel(II), chromium(III) and molybdenum(V) did not show any significant impact on these lymphocyte activation markers. Cell viability was significantly reduced by all metal ions, whereas cobalt(II) led to the highest increase of apoptotic cells and was the only metal ion to significantly increase the necrosis rate. While the pathophysiological significance of these findings remains unclear, they are in favour of further research in this field.

[Metal ion concentrations in patients with metal-metal bearings in prostheses]. / Metallkonzentrationen bei Patienten mit Metall-Metall-Gleitpaarungs-Prothese.

Increased wear leads to elevated systemic and local metal ion concentrations for patients treated with metal-on-metal bearings. The local metal ion content in the close environment of the joint replacement (e.g. joint aspirate or tissue) is several times higher compared to the systemic metal content (e.g. in blood or serum). As a result of increased metal ion levels, local and systemic effects, such as osteolysis, pseudotumors, sensitization or in rare cases toxicity may occur. Although the definition of a specific threshold to define clinical problems is difficult due to a lack of sensitivity, the systemic metal concentration is frequently measured clinically. Currently a threshold for cobalt and chromium between 4 µg/l and 7 µg/l is under debate. Very high levels (≥ 20 µg/l) or a steady increase over time should be a warning sign; however, metal ion levels should not be interpreted as a single diagnostic tool but rather in the entire context of the clinical, radiological and cross-sectional imaging, metal artefact reduction sequence (MARS) magnetic resonance imaging (MRI), ultrasound and computed tomography (CT) findings.

Placenta accreta spectrum in early and late pregnancy from an imaging perspective. A scoping review.

Placenta accreta spectrum (PAS) disorders (with increasing order of the depth of invasion: accreta, increta, percreta) are quite challenging for the purpose of diagnosis and treatment. Pathological examination or imaging evaluation are not very dependable when considered as stand-alone diagnostic tools. On the other hand, timely diagnosis is of great importance, as maternal and fetal mortality drastically increases if patient goes through the third phase of delivery in a not well-suited facility. A multidisciplinary approach for diagnosis (incorporating clinical, imaging, and pathological evaluation) is mandatory, particularly in complicated cases. For imaging evaluation, the diagnostic modality of choice in most scenarios is ultrasound (US) exam; patients are referred for MRI when US is equivocal, inconclusive, or not visualizing placenta properly. Herewith, we review the reported US and MRI features of PAS disorders (mainly focusing on MRI), going over the normal placental imaging and imaging pitfalls in each section, and lastly, covering the imaging findings of PAS disorders in the first trimester and cesarean section pregnancy (CSP).

Regulation of aggrecanases from the ADAMTS family and aggrecan neoepitope formation during in vitro chondrogenesis of human mesenchymal stem cells.

Aggrecanases from the ADAMTS (A Disintegrin And Metalloproteinase with ThromboSpondin motifs) family are important therapeutic targets due to their essential role in aggrecan depletion in arthritic diseases. Whether their function is also important for matrix rearrangements during chondrogenesis and thus, cartilage regeneration, is however so far unknown. The aim of this study was to analyse the expression and function of ADAMTS with aggrecanase activity during chondrogenic differentiation of human mesenchymal stem cells (MSCs). Chondrogenic differentiation was induced in bone marrow-derived MSC pellets and expression of COL2A1, aggrecan, ADAMTS1, 4, 5, 9, 16 and furin was followed by quantitative RT-PCR. Formation of the NITEGE (ADAMTS-cleaved) and DIPEN (MMP-cleaved) aggrecan neoepitopes was detected by immunohistochemistry. While the expression of ADAMTS4, 9, 16 and furin was up-regulated during chondrogenesis, ADAMTS1 and 5 were down-regulated. Despite this regulation of ADAMTS, no formation of NITEGE neoepitopes occurred in MSC pellets, indicating no ADAMTS-induced cleavage of aggrecan. In contrast, MMP-induced cleavage of aggrecan appeared at 14 d after induction of chondrogenesis. Submission of differentiated MSC pellets to IL1ß treatment for 3 d resulted in strong upregulation of ADAMTS1, 4 and 5, rapid proteoglycan depletion, and stimulation of ADAMTS-induced but not MMP-induced cleavage of aggrecan. Thus, there is no evidence for ADAMTS-induced aggrecan cleavage during chondrogenesis, but proteoglycan turnover is rapidly inducible under inflammatory signals. Therapeutic aggrecanase inhibition for treatment of arthritic disease may thus not impede regenerative self-healing pathways based on chondrogenesis of local progenitor cells in the joint.

The effect of polytrauma as a possible confounder in the outcome of monotraumatic vs polytraumatic paraplegic patients: a clinical cohort study.

STUDY DESIGN: Clinical cohort study. OBJECTIVE: To evaluate if the impact of the severity of the trauma as a possible confounding factor influences the neurological and functional recovery in paraplegia during the course of a 6-month follow-up period after injury. SETTING: Spinal Cord Injury Center, Heidelberg University Hospital, Germany. METHODS: A retrospective monocentric analysis, from 2002 to 2008, of the Heidelberg European Multicenter Study about spinal cord injury database was performed. We included 31 paraplegic patients (neurological level T1-T12) who were assigned either to a monotrauma (polytraumaschluessel (PTS) 1) or to a polytrauma (PTS≥2) group. The American Spinal Injury Association Impairment Scale, lower extremity motor score, pin prick, light touch and the spinal cord independence measure (SCIM) were obtained at five distinct time points after trauma. Data were analyzed using Mann-Whitney U-test (α<0.05). RESULTS: The changes in lower extremity motor score, pin prick and light touch showed no significant differences in both groups over the whole evaluation period. Polytraumatic paraplegics showed a significantly delayed increase of SCIM between 2 and 6 weeks compared with monotraumatic patients, followed by a quantitative increase in the subitems bladder management, bowel management, use of toilet and prevention of pressure sores between 3 and 6 months (P=0.031). The mean length of primary rehabilitation in the polytrauma group was 5.5 vs 3.6 months in monotrauma. CONCLUSIONS: The prognosis of polytraumatic paraplegics in terms of neurological recovery is not inferior to those with monotrauma. Multiple-injured patients need a prolonged hospital stay to reach the functional outcome of monotraumatic patients.

Proinflammatory cytokine gene single nucleotide polymorphisms in common variable immunodeficiency.

Common variable immunodeficiency (CVID) is a heterogeneous group of primary immunodeficiency diseases. Cytokine production could be affected in CVID patients, whereas its alteration could be due to genetic polymorphisms within coding and promoter regions of the cytokine genes. This study was performed to analyse the proinflammatory cytokine single nucleotide polymorphisms in CVID. The allele and genotype frequencies of a number polymorphic genes coding tumour necrosis factor (TNF)-alpha, interleukin (IL)-1alpha, IL-1beta, IL-1R, IL-1RA and IL-6 were investigated and compared between two groups of CVID patients and controls. The IL-6 GA genotype at position nt565 was significantly over-represented in the patient group (P<0.001), while the IL-6 GG genotype at position -174 (P=0.006) and the GG genotype at position nt565 (P<0.001) were significantly lower than controls. The TNF-alpha AG genotype at position -308 in the patient group was increased significantly in comparison with controls (P=0.027), but the GG genotype at the same position was significantly decreased (P=0.011). IL-6 CA and GA haplotypes were the most frequent haplotypes in the patients (P<0.005), whereas TNF-alpha GA (P=0.002) and IL-6 GG (P<0.001) haplotypes were decreased significantly in the patients in comparison with controls. Cytokine single nucleotide polymorphisms could have a role in pathophysiology of CVID. High production of TNF-alpha is expected in some CVID patients based on the frequency of genotypes/haplotypes of these cytokine gene polymorphisms.

Polymorphisms in IL4 and iLARA confer susceptibility to asthma.

BACKGROUND: Asthma is a complex disease that is caused by genetic and environmental factors. The production of interleukin (IL)-4, which can influence mast cell responsiveness to immunoglobulin (Ig) E--mediated signaling, could be modified by genetic variants in the IL-4 promoter. OBJECTIVE: To investigate the association between the IL-4 and IL-4RA promoter polymorphisms and asthma in a sample of Iranian patients. METHODS: We used polymerase chain reaction with sequence-specific primers to investigate the allele and genotype frequencies of 2 polymorphic genes coding for IL-4 and IL-4RA in 59 Iranian patients with asthma and 139 healthy controls. RESULTS: The most frequent genotypes in the patient group were IL-4TC (-590), IL-4TC (-33), IL-4 GT (-1098), and IL-4RA GA (+1902). In contrast, the frequencies of IL-4 CC (-590), IL-4 CC (-33), IL-4TT (-1098), and IL-4RAAA (+1902) were significantly lower in the patient group than in the control group. The most frequent haplotypes in our patients were IL-4 TCT and GTC at positions -1098,-590,-33. The mean total serum IgE level in patients with the TTT/GCC genotype was 258.8 IU/mL, which was significantly higher than the 95.4 IU/mL observed for other genotypes. CONCLUSION: We showed a strong association between the polymorphisms of the IL-4 gene promoter at positions -590, -33 and -1098 and bronchial asthma. We also demonstrated an association between their haplotypes and serum total IgE.

Toxocara eggs in public places worldwide - A systematic review and meta-analysis.

Toxocariasis is a neglected tropical disease of humans. Although many studies have indicated or shown that environmental contamination with Toxocara species eggs is a major risk factor for toxocariasis in humans, there has been no comprehensive analysis of published data or information. Here, we conducted the first systematic review and meta-analysis of current literature to assess the global prevalence of Toxocara eggs in public places (including beaches, parks and playgrounds). We conducted searches of the PubMed, Embase, Scopus and Science Direct databases for relevant studies published until 20 April 2018, and assessed the prevalence rates of Toxocara eggs in public places. We used the random effects model to calculate pooled prevalence estimates, with 95% confidence intervals (CIs), and analysed data in relation to WHO geographical regions. Subgroup analysis and meta-regressions regarding the geographical and environmental variables were also performed. Of 2384 publications identified, 109 studies that tested 42,797 soil samples in 40 countries were included in the meta-analysis. The pooled global prevalence of Toxocara eggs in public places was 21% (95% CI, 16-27%; 13,895/42,797). The estimated prevalence rates in the different WHO regions ranged from 13% to 35%: Western Pacific (35%; 95% CI, 15-58%), Africa (27%; 95% CI, 11-47%), South America (25%; 95% CI, 13-33%), South-East Asia (21%; 95% CI, 3-49%), Middle East and North Africa (18%; 95% CI, 11-24%), Europe (18%; 95% CI, 14-22%), and North and Central Americas (13%; 95% CI, 8-23%). A high prevalence was significantly associated with high geographical longitude (P = 0.04), low latitude (P = 0.02) and high relative environmental humidity (P = 0.04). This meta-analysis of data from published records indicates that public places are often heavily contaminated with eggs of Toxocara. This finding calls for measures to reduce the potential risk of infection and disease in humans.

The association of HLA-DRB, DQA1, DQB1 alleles and haplotype frequency in Iranian patients with pulmonary tuberculosis.

OBJECTIVES: To investigate HLA-DRB1, DQA1 and DQB1 allelic polymorphism in Iranian patients with pulmonary tuberculosis (PTB). METHODS: Forty patients with smear-positive PTB and 100 healthy individuals as a control group were studied for MHC class II allelic polymorphism by polymerase chain reaction with sequence-specific primers (PCR-SSP). The primer was supplied by biotest in the standard kit. DRB low resolution SSP and DQA, DQB intermediate resolution SSP was applied. RESULTS: The comparison of the patients and the control group showed a significant increase in the frequency of the HLA-DRB1*07 and DQA1*0101 alleles (OR 2.7, 95%CI 1.19-6.13, P = 0.025 and OR 2.66, 95%CI 1.15-6.44, P = 0.04, respectively) in the patient group. The frequency of DQA1*0301 and DQA1*0501 was also significantly decreased (OR 0.254, 95%CI 0.075-0.865, P = 0.033 and OR 0.53, 95%CI 0.3-0.95, P = 0.045, respectively) in the PTB patients. Concerning haplotype frequency, DRB1*11501, QDQA1*0103 and DQB1*0601 were increased, but this difference was not statistically significant. In the DQB1 locus, DQB1*0501 was non-significantly over-represented. CONCLUSIONS: HLA-DRB1*07 and HLA-DQA1*0101 appeared to be the predisposing alleles and HLA-DQA1*0301 and 0501 the protective alleles in our patients with TB.

FGF-2 addition during expansion of human bone marrow-derived stromal cells alters MSC surface marker distribution and chondrogenic differentiation potential.

OBJECTIVES: Although clinical applications using mesenchymal stromal cells (MSCs) are becoming more frequent, procedures for their in vitro culture are far from standardized. Growth factors such as FGF-2 are frequently added during expansion to improve population growth and differentiation characteristics. However, up to now its influence on surface marker distribution of MSCs has been close to unknown. The purpose of this study was therefore to analyse effects of FGF-2 supplementation on pre-selection of MSC subpopulations. MATERIALS AND METHODS: Mesenchymal stromal cells were harvested from bone marrow of six patients and expanded in alpha-MEM or DMEM-LG. Starting in passage 2, 10 ng/ml FGF-2 was administered and non-supplemented media were used as controls. Growth indices were calculated from P0 to P4. After P4, fluorescence cytometry for common MSC surface markers was performed and standard chondrogenic, adipogenic and osteogenic differentiation protocols were applied. RESULTS: Cell population growth indices were higher for those in FGF-2 supplemented media. Significant differences in surface marker distribution were observed for CD13, CD14, CD49, CD90, CD340 and STRO-1 depending on respective culture conditions. FGF-2 suppressed CD146 expression in both alpha-MEM and DMEM-LG. No differences in adipogenic and osteogenic differentiation potential could be observed, while FGF-2 significantly improved chondrogenic differentiation in DMEM-LG. CONCLUSIONS: While holding the benefit of improving MSC chondrogenic differentiation potential, FGF-2 pre-selects certain MSC subtypes. Our data clearly show that expansion culture conditions have a significant effect on distribution of a number of MSC surface markers.