Effect of Ultrasound Therapy on Expression of Vascular Endothelial Growth Factor, Vascular Endothelial Growth Factor Receptors, CD31 and Functional Recovery After Facial Nerve Injury.

Functional recovery is provided by some neurotrophic factors released from the near vicinity of the injury site. Ultrasound treatment is known to increase neurotrophic factor expression. This study was aimed at determining the effect of ultrasound treatment on the expression of vascular endothelial growth factor (VEGF), its receptors and new vessel formation after facial nerve injury. Sixty-four Wistar rats were divided into four groups: control (group 1), sham (group 2), facial-facial coaptation (group 3), and facial-facial coaptation and ultrasound treatment (group 4). Animals in each group were evaluated on the 14th and 28th days. Immunohistochemical staining and electrophysiological and gene-level evaluations were performed for the expression of VEGF and its receptors. When the results were evaluated, it was determined that VEGF, VEGFR1 (VEGF receptor 1), VEGFR2 (VEGF receptor 2) and CD31 levels were significantly higher in groups 3 and 4 compared with the control and sham groups. The increase in these values was more prominent after 28 d of ultrasound treatment than all groups. Electrophysiological results revealed similar evident functional improvement in group 4 with decreased latency and increased amplitudes compared with group 3. Our findings suggest that ultrasound treatment might promote injured facial nerve regeneration by stimulating release of VEGF and its receptors and may result in functional improvement.

Articular chondroprogenitors in platelet rich plasma for treatment of osteoarthritis and osteochondral defects in a rabbit knee model.

BACKGROUND: Articular chondroprogenitors are a promising contender for cartilage repair due to their inherent nature which stands primed for chondrogenesis and minimal hypertrophic preponderance. Platelet rich plasma (PRP) has been extensively used for treating cartilage defects and osteoarthritis (OA), due to its chondro-inductive properties and abundant pool of growth factors. The aim of this study was to assess the efficacy of chondroprogenitors injected with PRP versus PRP alone in the healing of experimentally created early OA and osteochondral defects (OCD) in a rabbit model. METHODS: Adult New Zealand White male rabbits were used for cell and PRP isolation. Chondroprogenitors were isolated by fibronectin adhesion assay, labelled with iron oxide, characterized for surface markers, differential potential and expanded. PRP was isolated by double spin centrifugation using a TriCell kit. Study groups included (a) Monosodium iodoacetate induced early OA and (b) critical OCD. Following intervention (test arm: PRP+ chondroprogenitors and control arm: PRP), assessment was performed at 6- and 12-weeks which included histopathological examination and scoring (OARSI and Modified Wakitani score), immunohistochemistry analysis (Collagen type II and X) and synovial fluid S100A12 levels. RESULTS AND CONCLUSION: Comparable, evident healing was noticed in both test and control arms when the OA group samples were assessed at both time points. In the OCD group, PRP alone exhibited significantly better results than the test arm, although repair was notable in both interventions. Further evaluation of chondroprogenitors is required to assess their role as a standalone therapy and in combination with PRP to further cartilage regeneration.

The effect of experimental varicocele on the apelin and APJ expressions in rat testis tissue.

Varicocele, which is one of the causes of infertility in men, can be defined as the expansion of spermatic cord veins. The presence of apelin and apelin receptor (APJ) in many tissues and the effects of apelin have been reported in several studies. There is no study showing apelin and APJ protein expressions in normal and varicocele-induced testicular tissues. In this study, we aimed to demonstrate varicocele-induced changes in apelin and APJ expressions in testicular tissue by immunohistochemical and western blotting techniques. In our study, Wistar male rats were randomly divided into three groups as control, varicocele, and sham. While the control group rats were not subjected to any treatment, the unilateral varicocele model was created under anesthesia in the varicocele group. In the sham group, the left abdominal region was opened and closed to exclude the effect of the surgical procedure. At the 13th postoperative week, the left testes were obtained under anesthesia in all groups, and the immunohistochemistry and Western blotting techniques were used to detect apelin and APJ expressions. In our study; apelin and APJ were significantly expressed in control group's testicular tissue; apelin in testicular tissues of varicocele groups increased compared to the control group, whereas APJ expression decreased. In conclusion, the presence of apelin/APJ system in normal testis and the increased expression of apelin in varicocele-induced testicular tissue suggested that apelin may have a role in the varicocele etiopathogenesis.

Optimization of immunohistochemical detection of collagen type II in osteochondral sections by comparing decalcification and antigen retrieval agent combinations.

Bone containing tissues such as osteochondral joint are resistant to routine tissue processing, therefore require decalcification. This technique causes removal of mineral salts, but in the process may macerate the organic tissue, hence the need for tissue fixation. Such severe processing demands careful antigen retrieval to necessitate optimal staining. The aim of our study was to compare five different antigen retrieval protocols (heat retrieval and protein digestion) following decalcification of rabbit knee joints using two different techniques (20% formic acid and 10% ethylenediamine-tetra acetic acid: EDTA). Osteochondral sections were compared based on time required for decalcification, ease of sectioning, morphological integrity using HE staining and antigen preservation (Collagen type II) using immunohistochemistry. The two decalcification solutions did not impair the tissue morphology and ease of sectioning. Joints processed with formic acid decalcified four times faster than EDTA. Among the five antigen retrieval approaches, maximal collagen II uptake with minimal nonspecific staining was found with protein digestion (pronase and hyaluronidase) in both formic acid and EDTA sections. For osteo-chondral sections, we recommend using 10% EDTA for decalcification and pronase plus hyaluronidase for antigen retrieval if maintaining tissue morphology is crucial, whereas if time is of the essence, 20% FA with pronase plus hyaluronidase is the faster option while still preserving structural integrity. Clin. Anat. 33:343-349, 2020. © 2019 Wiley Periodicals, Inc.

Comparison of human articular chondrocyte and chondroprogenitor cocultures and monocultures: To assess chondrogenic potential and markers of hypertrophy.

BACKGROUND AND OBJECTIVE: In the field of cartilage repair, use of two or more cell populations such as mesenchymal stem cells with chondrocytes in an in-vitro co-culture synergistic environment has been attempted to evade limitations of monoculture systems and promote/induce chondrogenesis. Articular cartilage-derived chondroprogenitors (CPs), considered to have stem-cell like characteristics have been proposed as a potential contender for neocartilage development. Our objective was to assess whether co-cultures using different ratios of chondrocytes(C) and CPs would demonstrate better results in terms of growth kinetics, surface marker expression, chondrogenic potential, tendency for hypertrophy and glycosaminoglycan deposition than monocultures. STUDY DESIGN: Human chondrocytes and CPs (fibronectin adhesion assay) from the same cartilage source were isolated. Passage 2 cells were subjected to monolayer/pellet cultures and were grown as monocultures and cocultures at the following percentage ratios(C:CP) 80:20, 65:35, 50:50, 35:65 and 20:80. RESULTS: Analysis of data acquired from population doubling, flow cytometry, RT-PCR and Safranin O uptake demonstrated similar results in all monoculture and co-culture groups with no significant inter-group variation, even when reported specific markers of identification (CD54 and CD44:chondrocyte markers) and isolation (CD29 and CD49e: forming heterodimeric fibronectin receptor for CP sorting) were examined. CONCLUSION: In conclusion, this study suggests the need for improved sorting techniques based on a characteristic differentiating biomarker for selection of cells which are true representatives of CPs possessing properties of enhanced chondrogenesis and reduced hypertrophy.

Apelin-APJ system is responsible for stress-induced increase in atrial natriuretic peptide expression in rat heart.

BACKGROUND: The cardiovascular system is a primary target of stress and stress is the most important etiologic factor in cardiovascular diseases. Stressors increase expressions of atrial natriuretic peptide (ANP) and apelin in cardiac tissue. AIM: The aim of the present study was to investigate whether stress-induced apelin has an effect on the expression of ANP in the right atrium of rat heart. METHODS: The rats were divided into the control, stress and F13A+stress groups. In the stress and F13A+stress groups, the rats were subjected to water immersion and restraint stress (WIRS) for 6h. In the F13A+stress group, apelin receptor antagonist F13A, was injected intravenously immediately before application of WIRS. The plasma samples were obtained for the measurement of corticosterone and atrial natriuretic peptide. The atrial samples were used for immunohistochemistry and western blot analysis. RESULTS: F13A administration prevented the rise of plasma corticosterone and ANP levels induced by WIRS. While WIRS application increased the expressions of apelin, HIF-1α and ANP in atrial tissue, while F13A prevented the stress-induced increase in the expression of HIF-1α and ANP. CONCLUSION: Stress-induced apelin induces ANP expression in atrial tissue and may play a role in cardiovascular homeostasis by increasing ANP expression under WIRS conditions.

Characterization of Notch Signalling Pathway Members in Normal Prostate, Prostatic Intraepithelial Neoplasia (PIN) and Prostatic Adenocarcinoma.

Prostate Cancer (PCa) holds the second place in terms of cancer-related mortality rate among men. The Notch signalling pathway regulates the proliferation and differentiation in embryonic and adult tissues and determines the cell fate. The body of knowledge in the present literature is currently controversial about the effect of the Notch pathway on prostatic cancer. Therefore, the present study aimed to examine the immunolocalization and expression levels of Notch1-4, Jagged1-2, Delta, HES1 and HES5 from among the members of the Notch signalling pathway in tissues of normal, prostatic intraepithelial neoplasia (PIN) and malignant prostate. The current study included a sample of 20 patients with localised prostatic adenocarcinoma, 18 patients with high grade PIN (H-PIN) and 18 normal prostatic tissue. Immunolocalisations of Notch1, 2, 3, 4, Jagged1, 2, Delta, HES1 and HES5 were identified through the immunohistochemical method. The findings of the present study showed that all in-scope members of the Notch signalling pathway were localised in PIN structures to a greater extent than in other tissues and from amongst these members, specifically Notch1, Notch4, Jagged1 and HES1 were at more significant levels. Consequently, the findings of the present study may indicate that the Notch signalling pathway can play a role especially in the formation of PIN structures.

The determination of apoptosis rates on articular cartilages of ovariectomized rats with and without alendronate treatment.

Osteoporosis (OP) is a major health problem characterized by compromised bone strength. Osteoarthritis (OA) is a joint disease that progresses slowly and is characterized by breakdown of the cartilage matrix. Alendronate (ALN), a nitrogen-containing bisphosphonate (BIS), inhibits bone loss and increases bone mineralization, and has been used clinically for the treatment of OP. It is still controversial whether BIS is effective in inhibiting the progression of OA. Chondrocyte apoptosis has been described in both human and experimentally induced OA models. In our study we aimed to detect whether ALN could protect articular cartilage from degeneration and reduce apoptosis rates in experimentally OA induced rats. For this rats were ovariectomized (ovex), nine weeks after operation rats were injected 30 µg/kg/week ALN subcutaneously for six weeks. After six weeks articular cartilages were obtained. We did Safranin O staining and Mankin and Pritzker scorings to evaluate degeneration and investigated the expressions of p53, cleaved caspase 3, Poly ADP-ribose (PAR), Poly ADP-ribose polymerase 1 (PARP 1), and applied TUNEL technique to determine apoptotis rates. We found a significant decrease in glycosaminoglycan (GAG) amount and increased apoptosis which indicates damage on articular cartilages of ovex rats. GAG amount was higher and apoptosis rate was lower on articular cartilages of ALN treated ovex rats compared to the ovex group. In contrary to studies showing that early ALN treatment has a protective effect, our study shows late ALN treatment has a chondroprotective effect on articular cartilage since we treated rats nine weeks after ovariectomy.

Expression of nuclear factor erythroid 2-related factor 2 (Nrf2) and peroxiredoxin 6 (Prdx6) proteins in healthy and pathologic placentas of human and rat.

A relationship has been shown between preeclampsia (PE) and intrauterine growth restriction (IUGR) and oxidative stress (OS). Since such pregnancies experience OS, we aimed to detect the distribution pattern and expression levels of a transcription factor, Nuclear factor erythroid 2-related factor-2 (Nrf2) that has a role in the regulation of antioxidant enzymes, and peroxiredoxin 6 (Prdx6) an antioxidant enzyme, in human healthy, IUGR, PE and in groups of rat healthy and IUGR placentas using immunohistochemistry and Western blotting. Both Nrf2 and Prdx6 immunoreactivities were weaker in human and rat IUGR group placentas compared to human and rat control group placentas, respectively. Nrf2 and Prdx6 were immunostained in labyrinth trophoblasts, decidua, giant, glycogen and fetal vessel endothelial cells in rat control and IUGR group placentas. Nrf2 and Prdx6 immunoreactivities were seen in the decidua, syncytiotrophoblasts, villous stromal cells, and vascular endothelium in human control, IUGR and PE group placentas. Results of Nrf2 and Prdx6 Western blotting applied for rat and human placentas were compatible with the results of Nrf2 and Prdx6 immunohistochemical observations with regard to rat and human placentas. Down-regulation of Nrf2 and Prdx6 proteins in human and rat IUGR group placentas may have led to the formation of OS which may have impaired proliferation and invasion of cytotrophoblasts.

Characterization of colony-forming cells in adult human articular cartilage.

Recent studies have shown that adult human articular cartilage contains stem-like cells within the native structure. In this study, we aimed to determine the localization of putative stem cell markers such as CD90, STRO-1, OCT-3/4, CD105 and CD166 in adult human articular cartilage tissue sections and demonstrate the expression of these markers within the expanded surface zone colony-forming (CF) cells and evaluate their differentiation potential. Biopsy samples were either fixed immediately for immunohistochemical analyses or processed for in vitro cell culture. Immunohistochemical and flow cytometry analyses were performed by using CD90, STRO-1, OCT-3/4, CD105 and CD166 antibodies. Isolated colony-forming (CF) cells were further stimulated, by using the appropriate growth factors in their pellet culture, to obtain cartilage, bone and adipose lineages. We observed that the expression of the stem cell markers were in various zones of the human adult cartilage. Flow cytometry results showed that in CF cells the expression of CD90 and CD166 was high, while OCT-3/4 was low. We also determined that CF cells could be stimulated towards cartilage, bone and adipose lineages. The results of this research support the idea that the resident stem-like cells in adult human articular cartilage express these putative stem cell markers, but further experimental investigations are needed to determine the precise localization of these cells.

The effects of water immersion and restraint stress on the expressions of apelin, apelin receptor (APJR) and apoptosis rate in the rat heart.

Apelin has been identified as an endogenous ligand of the orphan G-protein-coupled apelin receptor (APJR). These receptors are widely expressed in the central nervous system and periphery and play a role in the regulation of fluid and glucose homeostasis, feeding behavior, vessel formation, cell proliferation and immunity. We aimed to investigate whether water immersion and restraint stress have effects on apelin and APJR expression and apoptosis in heart tissue of male Wistar rats. The cardiac tissues were obtained from control, water immersion and restraint stress (WIRS) and apelin antagonist (F13A)+WIRS groups of rats and embedded in paraffin wax. Immunohistochemical staining methods were used to localize apelin, APJR and TUNEL immunopositive cells. H-SCORE was used for semi-quantitative determinations. Apelin protein levels were determined by Western blot in the cardiac tissues and plasma corticosteroid levels were measured by enzyme immunoassay (EIA). Apelin immunolocalization was found especially in endothelial cells and mast cells and faintly in cardiomyocytes, APJR immunostaining was shown in endothelial cells and cardiomyocytes, and TUNEL reaction was observed in endothelial cells and in some fibroblasts. Apelin expression was significantly increased in the WIRS and F13A+WIRS groups compared to the control group. The APJR reaction was similar in all groups. The number of TUNEL-positive cells was significantly higher in the F13A+WIRS group than that of the control group. Our study showed that WIRS for 6h increased plasma corticosterone levels and cardiac apelin expression in rats. The increased levels of apelin inhibited stress-induced apoptosis in heart. These results may be important for the therapeutic approach to a variety of stress-related heart disease.

Protective effect of zoledronic acid on corticosteroid-induced chondrocyte apoptosis in rat articular cartilage.

OBJECTIVE: The aim of this study was to assess the apoptotic effects of systemic corticosteroid application on the articular cartilage chondrocytes in vivo and to investigate the potential effects of zoledronic acid on corticosteroid-induced apoptosis. METHODS: Twenty-four Wistar rats were randomly divided into 3 groups. In the control group, intramuscular isotonic salt solution was injected weekly. In the second group, a dose of 10 mg/kg intramuscular corticosteroid (methylprednisolone) injection was applied weekly for 8 weeks. In the third group, a dose of 10 mg/kg intramuscular corticosteroid (methylprednisolone) injection was applied weekly for 8 weeks and 0.1 mg/kg zoledronic acid was injected subcutaneously on days 0, 21 and 42. Femoral head specimens from each group were obtained at the end of the treatment and the TUNEL method was applied to detect apoptotic chondrocytes. Comparison analyses were performed using the ANOVA method and Tukey's test. RESULTS: There was a significant difference between the corticosteroid group and two other groups (control group: p=0.005; corticosteroid + zoledronic acid group: p=0.047). Zoledronic acid treatment significantly decreased the number of corticosteroid-induced apoptotic chondrocytes in the joint cartilage (p<0.05). CONCLUSION: Zoledronic acid may have the potential to prevent joint cartilage deterioration due to the corticosteroid-induced apoptosis of the chondrocytes.

[Does application time of alendronate sodium effect the spinal fusion in ovariectomized rats?]. / Alendronate sodyum uygulama zamani, ovariyektomi yapilmis siçanlarda spinal füzyon üzerine etkili midir?

OBJECTIVES: In this experimental study the effect of alendronate (Aln) sodium on spinal fusion, that was given preoperatively or postoperatively, was compared both mechanically and histologically in ovariectomized rats. The research question was "Does application time of alendronate sodium effect the spinal fusion in ovariectomized rats?''. MATERIALS AND METHODS: Fifty female Wistar rats with a mean weight of 200 g and an average age of 12 weeks were ovariectomized according to the standard procedure. The rats were randomized into three groups nine weeks after ovariectomy. Group 1: spinal arthrodesis and saline weekly for six weeks postoperatively; group 2: spinal arthrodesis and Aln sodium 1 µgr/kg/week for six weeks postoperatively; group 3: Aln sodium 1 µgr/kg/week for six weeks preoperatively, then one week later spinal arthrodesis was done. The rats were sacrificed six weeks after fusion surgery and their vertebrae were evaluated by manual palpation, mechanical testing machine and histomorphometric analysis. RESULTS: Fusion rates obtained by manual palpation were 50%, 17.6% and 55.5% in group 1, 2 and 3, respectively (p>0.05). Mean values of fusion tissues in mechanical evaluation were 498±20.7, 481±23.7 and 480±26.2 (MPa) accordingly (p>0.05). Compared with group 1, delayed endochondral ossification and more cartilage matrix among bone grafts were seen in group 2 and 3 in histological evaluation. CONCLUSION: Application time of the Aln sodium didn't significantly affect the lumbar spinal fusion rates in ovariectomized rats. In histological evaluation, delayed endochondral ossification was seen in Aln sodium-treated groups.

Distribution of Notch family proteins in intrauterine growth restriction and hypertension complicated human term placentas.

Members of the Notch family have been detected in many developmental and cell specification processes during placental development. However, Notch protein expression in Intrauterine Growth Restriction (IUGR) and Pregnancy Induced Hypertension (PIH) is not clear. In this study we aimed to clarify the immunolocalization of Notch proteins in full-term placentas after IUGR and PIH in comparison with normal placentas. Formalin-fixed, paraffin-embedded term placentas obtained by caesarean operations were processed for immunohistochemical localization of Notch 1, 2, 4 and Jagged 2. Transmission electron microscopy was also performed. In normal term placentas, all Notch proteins were intensely immunostained in the brush border of cells of the syncytiotrophoblast layer of the basal (maternal) side and the chorionic plate (fetal) side. The endothelial cells were also intensely immunostained in both sides for Notch 1. However, in IUGR and PIH placentas, the immunoreactivities of all Notch proteins were decreased significantly in the brush border of cells of the syncytiotrophoblast layer and the reaction was generally observed in the cytoplasm of syncytiotrophoblast cells in the basal and chorionic plate sides. The reactivity in endothelial cells was also significantly decreased. Our results have shown that the immunoreactivity and localization of Notch proteins is altered in pathologic placentas. Therefore, we propose that deregulated expression of Notch proteins may contribute to the disruption of trophoblast differentiation, endothelial cell function and/or feto-maternal traffic down-regulation during pregnancy or vice versa in such pathologic conditions.

Distribution of CD105 and CD166 positive cells in the proximal epiphysis of developing rat humerus.

The expression of cell surface receptors, CD105 and CD166, are characteristic of mesenchymal stem cells in cartilage. However, there is limited data regarding their immunolocalization in the cartilage of developing rat epiphysis. The purpose of this study was to determine the presence of CD105 and CD 166 positive cells in the proximal epiphysis of developing rat humerus and specify their zonal distribution with age. The tissues of rat humerus were taken on embryonic day 15 (E15), embryonic day 19 (E19), postnatal day 10 (PN10), postnatal day 20 (PN20) and adult rats and studied for the immunolocalization of CD105 and CD166. Our results showed that CD105 and CD166 positive cells were scattered in early stages of development of humerus epiphysis. For E15, only the hypertrophic zone was positive, whereas for E19 almost all zones of the epiphysis were positively stained for these markers. For PN10 and PN20, the CD105 and CD166 positive cells were mainly localized on the surface of the articular cartilage. In adult articular cartilage the CD105 and CD166 positive cells were localized in the superficial and transitional zones and in the upper regions of the deep zone. Our study provides evidence that in the developing cartilage tissue the localization of CD105 and CD166 positive cells is both dynamic and stage dependent, which may imply the existence of stem cell-like cells in cartilage from an early age to adult.

The effect of systemic corticosteroid treatment on the immunolocalisation of Notch-1, Delta, CD105 and CD166 in rat articular cartilage.

We studied the immunolocalisation of the stem cell-specific markers Notch-1, Delta, CD105 and CD166 in rat articular cartilage and analysed the effect of systemic corticosteroid treatment on the patterns of distribution of cells labelling for these markers. Female Wistar rats were separated randomly into two groups: the control group (n=8) was injected with isotonic salt solution and the corticosteroid group (n=8) was injected with 10 mg/kg intramuscular corticosteroid (methylprednisolone) once a week for a period of 8 weeks. Femoral head specimens from each group were obtained at the end of the treatment and processed for routine histological and immunohistochemical examinations. Quantitative data were obtained by H-SCORE and statistical evaluations were performed. The immunolocalisation of all markers was more apparent in the superficial zone and decreased through the deeper zones in all groups. However, the intensity of labelling was much less obvious in the group treated with corticosteroid compared to control. H-SCORE analysis confirmed that in the group treated with corticosteroid, the intensity of Notch-1, Delta, CD105 and CD166 labelling had decreased significantly compared to control (p<0.05). In conclusion, based on the immunolocalisation of stem cell-specific markers Notch-1, Delta, CD105 and CD166, the data suggest that the stem cells may continue to exist in adult rat articular cartilage. It was also observed that systemic corticosteroid treatment may effect the immunolabelling intensity of these markers, suggesting that corticosteroid treatment may reduce the function and the regenerative capacity of these cells in articular cartilage.

The immunohistochemical localization of notch receptors and ligands in human articular cartilage, chondroprogenitor culture and ultrastructural characteristics of these progenitor cells.

The presence of progenitor/stem cells in human articular cartilage remains controversial. Therefore, we attempted to isolate and culture progenitor/stem cells and to investigate their phenotypic characteristics. Biopsies were obtained (with consent) from patients undergoing arthroscopic surgery. Full depth explants were fixed and cryosectioned or enzymatically digested and the resulting cells cultured and plated on fibronectin-coated dishes. Chondrocytes were cultured until colonies of >32 cells were present. Colonies were trypsinized and expanded in monolayer for pellet culture. Immunolocalization of Notch and its ligands were detected in vivo and in vitro using immunocytochemistry. In vitro studies investigated differences in immunolocalization of Notch and its associated ligands in colony-forming cells and small clusters of non-colony-forming cells. The ultrastructure of the chondroprogenitors was examined by scanning and transmission electron microscopy. Results revealed that the immunolocalization of Notch-1 and its ligand Delta were concentrated in regions closest to the articular surface. Notch-1 was also densely localized in the deeper zone of articular cartilage. Notch-2 immunolabeling was densely localized in all zones of articular cartilage. Jagged-1 was concentrated in the deeper regions of articular cartilage. Notch-1, Delta and Jagged-1 were more abundant in colony-forming cells than non-colony-forming chondrocytes in vitro. Notch-3, Notch-4 and Jagged-2 were absent from all regions of the articular cartilage tissues and cultured cartilage cells in vitro. Ultrastructurally, chondrocytes cultured in monolayer dedifferentiated to fibroblast-like cells with cell surface processes of varying lengths, pellet cultured cells varied in morphology, as flattened and rounded. In conclusion, we propose that adult human articular cartilage may contain cells having progenitor cell features.