Collagen sponges for bone regeneration with rhBMP-2.

Matrigel: From discovery and ECM mimicry to assays and models for cancer research

Objective. To establish a model and associated molecular markers for monitoring the capacity of in vitro‐expanded chondrocytes to generate stable cartilage in vivo. Methods. Adult human articular chondrocytes (AHAC) were prepared by collagenase digestion of samples obtained postmortem and were expanded in monolayer. Upon passaging, aliquots of chondrocyte suspensions were either injected intramuscularly into nude mice, cultured in agarose, or used for gene expression analysis. Cartilage formation in vivo was documented by histology, histochemistry, immunofluorescence for type II collagen, and proteoglycan analysis by 35 S-sulfate incorporation and molecular sieve chromatography of the radiolabeled macromolecules. In situ hybridization for species-specific genomic repeats was used to discriminate human-derived from mousederived cells. Gene expression dynamics were analyzed by semiquantitative reverse transcription‐polymerase chain reaction. Results. Intramuscular injection of freshly isolated AHAC into nude mice resulted in stable cartilage implants that were resistant to mineralization, vascular invasion, and replacement by bone. In vitro expansion of AHAC resulted in the loss of in vivo cartilage formation. This capacity was positively associated with the expression of fibroblast growth factor receptor 3, bone morphogenetic protein 2, and a1(II) collagen (COL2A1), and its loss was marked by the up-regulation of activin receptor‐like kinase 1 messenger RNA. Anchorageindependent growth and the reexpression of COL2A1 in agarose culture were insufficient to predict cartilage formation in vivo. Conclusion. AHAC have a finite capacity to form stable cartilage in vivo; this capacity is lost throughout passaging and can be monitored using a nude mouse model and associated molecular markers. This cartilageforming ability in vivo may be pivotal for successful cell-based joint surface defect repair protocols.

https://onlinelibrary.wiley.com/doi/pdf/10.1002/1529-0131%28200107%2944%3A7%3C1608%3A%3AAID-ART284%3E3.0.CO%3B2-T

Molecular markers predictive of the capacity of expanded human articular chondrocytes to form stable cartilage in vivo

Potential applications and delivery strategies for bone morphogenetic proteins.

Helicobacter pylori (H. pylori) is an extremely common, yet underappreciated, pathogen that is able to alter host physiology and subvert the host immune response, allowing it to persist for the life of the host. H. pylori is the primary cause of peptic ulcers and gastric cancer. In the United States, the annual cost associated with peptic ulcer disease is estimated to be $6 billion and gastric cancer kills over 700000 people per year globally. The prevalence of H. pylori infection remains high (> 50%) in much of the world, although the infection rates are dropping in some developed nations. The drop in H. pylori prevalence could be a double-edged sword, reducing the incidence of gastric diseases while increasing the risk of allergies and esophageal diseases. The list of diseases potentially caused by H. pylori continues to grow; however, mechanistic explanations of how H. pylori could contribute to extragastric diseases lag far behind clinical studies. A number of host factors and H. pylori virulence factors act in concert to determine which individuals are at the highest risk of disease. These include bacterial cytotoxins and polymorphisms in host genes responsible for directing the immune response. This review discusses the latest advances in H. pylori pathogenesis, diagnosis, and treatment. Up-to-date information on correlations between H. pylori and extragastric diseases is also provided.

Beyond the stomach: an updated view of Helicobacter pylori pathogenesis, diagnosis, and treatment.

Nasal polyps recur in approximately one-third of patients after surgical treatment. It would be beneficial to be able to predict the patients in whom we might expect recurrence and to predict the clinical outcome after surgery. The study included 30 patients operated for nasal polyps. Removed polyps were analyzed by immunohistochemical analysis for IL-5, IgE, vascular endothelial growth factor and eosinophilic infiltration. These parameters together with preoperative CT score were used as independent variables, and subjective score improvement after 2 years was used as a dependent variable in multiple linear regression analysis. Furthermore, the patients were divided into two groups: low and high polyp tissue immunoreactivity. The Chi-squared test was used to determine whether polyp immunoreactivity influences polyp recurrence and subjective score. Preoperative CT score had a slightly positive correlation with subjective score after 2 years. High eosinophil infiltration significantly predicted a higher risk for polyp recurrence. High IL-5 positivity was related to greater risk for polyp recurrence than low IL-5 reactivity but not significantly. IgE and VEGF reactivity in polyp specimens did not have any effect on polyp recurrence. High eosinophilic infiltration in polyps can predict worse outcome after surgical treatment of chronic rhinosinusitis with nasal polyposis. IgE and VEGF do not have prognostic significance to polyp recurrence after surgery. The preoperative extent of disease measured by CT score had a slightly positive correlation with worse outcome after surgery.

Surgical treatment for nasal polyposis: predictors of outcome

Osteogenic protein-1 (OP-1, BMP-7), a member of the transforming growth factor-beta family, induces cartilage and bone formation when implanted at intra and extraskeletal sites in vivo. The human OP-1 gene has been cloned and biologically active recombinant OP-1 homodimers have been produced. In the present study, the authors investigated the influence of OP-1 on healing of full-thickness articular cartilage defects, made by drilling two adjacent (phi 3mm) holes through articular cartilage of NZW rabbit knee joint were dissected and examined histomorphometrically. Results indicated that OP-1 induced articular cartilage healing and regeneration of the joint surface which contained cells resembling mature joint chondrocytes. These data imply a new strategy for biological repair of damaged joint surfaces in humans.

Regeneration of articular cartilage defects in rabbits by osteogenic protein-1 (bone morphogenetic protein-7).

OBJECTIVE: To estimate the predictable value of histopathologic parameters in chronic rhinosinusitis (CRS) for response to endoscopic sinus surgery (ESS).STUDY DESIGN: Symptomatology was rated in 100 patients prior to as well as 12 and 24 months after surgery. Specimens taken during the procedure were examined and scored for goblet cells, subepithelial thickening, mast cells, and eosinophils. Multiple regression analysis was performed to predict the total score of subjective symptoms before treatment by histopathologic parameters. The correlation between histopathologic parameters and postoperative symptoms was then evaluated.RESULTS: Goblet cells were the best predictor correlating with 5 symptoms. Subepithelial thickening correlated with 4 symptoms. Mast cell infiltration correlated with 3 symptoms. Eosinophilic infiltration correlated with only one symptom (P < 0.05).CONCLUSION: Certain histopathologic parameters in CRS are predictive of favorable response to ESS.SIGNIFICANCE: Pathologic evaluation may...

Histopathologic parameters as predictors of response to endoscopic sinus surgery in nonallergic patients with chronic rhinosinusitis.

Objective of this study was to test whether there is a difference between chronic rhinosinusitis patients with (CRSwNP) and without (CRSsNP) nasal polyps in the association of extent of disease on CT scans with symptom severity and health-related quality-of-life (HRQL) impairment. Data sets from 271 chronic rhinosinusitis (CRS) patients who completed the Sino-Nasal Outcome Test 22 (SNOT-22) and visual analog scale (VAS) scores were subjected to principal component analysis (PCA) to identify a symptom components related to CRS. After controlling for demographics, medical therapy, and comorbidities, the association between symptom components/items excluded from PCA and Lund-Mackay score (LMS) was evaluated. No association was found between the total SNOT-22 score and LMS in CRS patients. There was an independent association between a higher "nasal" symptom component derived from SNOT-22 PCA and LMS in patients with CRSwNP (p < 0.001), but not in CRSsNP patients, with a statistically significant difference between two patient subsets (p = 0.003). In patients with CRSsNP, higher (worse) SNOT-22 "facial pain" was associated with lower LMS (p = 0.022), although the estimated change in LMS was modest. Considering VAS PCA components, higher "nasal" symptoms were associated with higher LMS in CRSwNP patients (p < 0.001) but not in CRSsNP, with a statistically significant difference between CRS groups (p = 0.024). A higher "pain" PCA component was associated with lower LMS in CRSsNP patients (p = 0.019). This study found significant differences in the relationship between symptom burden and CT scores between CRS phenotypes and no association between HRQL impairment and CT scores.

Association between computed tomography findings and clinical symptoms in chronic rhinosinusitis with and without nasal polyps

Primary cultures of fetal rat calvarial cells contain a spectrum of osteogenic phenotypes including undifferentiated mesenchymal cells, osteoprogenitor cells, and osteoblasts. We recently demonstrated that rat calvarial osteoblast-like cells grown on basement membrane undergo profound morphological changes resembling a canalicular network in bone. In the present study, we examined the effect of reconstituted basement membrane Matrigel on chondroblastic versus osteoblastic differentiation of different cell subpopulations obtained by five consecutive enzymatic digestions of rat calvarial cell populations. We found that the appearance of canalicular cell processes decreased with the later digests. When cells from the fourth and fifth digest were grown on top of Matrigel for 7 days, the majority of the cell aggregates displayed chondrocytic characteristics but none of the cells became hypertrophic. When individual chondroblastic cell aggregates were subsequently transferred from Matrigel to plastic, they started expressing types I and X collagens, alkaline phosphatase, and osteocalcin. Within the next 7 days (days 8-14 of the experiment), the majority of cells increased in size, and at day 17 on plastic (day 24 of the experiment) mineralized bone nodules formed. The chondroblastic differentiation of calvarial cells grown on Matrigel could be inhibited by a specific transforming growth factor-beta 1 (TGF-beta 1) but not by a TGF-beta 2 antibody. Addition of recombinant TGF-beta 1 to similar cultures promoted the appearance of chondroblastic cell aggregates. The cartilage phenotype could not, on the contrary, be promoted by growing the cells on other extracellular matrices such as a collagen I gel. We suggest that TGF-beta 1 in concert with the basement membrane extracellular matrix induces chondroblastic differentiation of rat calvarial osteoprogenitor cells.

Marko Grgić

Papers

Surgical treatment for nasal polyposis: predictors of outcome

Regeneration of articular cartilage defects in rabbits by osteogenic protein-1 (bone morphogenetic protein-7).

Histopathologic parameters as predictors of response to endoscopic sinus surgery in nonallergic patients with chronic rhinosinusitis.

Association between computed tomography findings and clinical symptoms in chronic rhinosinusitis with and without nasal polyps

TGF-β and basement membrane matrigel stimulate the chondrogenic phenotype in osteoblastic cells derived from fetal rat calvaria