Evaluation of the Complex Transcriptional Topography of Mesenchymal Stem Cell Chondrogenesis for Cartilage Tissue Engineering

Mesenchymal stem cells (MSCs) are a promising cell source for cartilage tissue engineering given their chondrogenic potential. This potential has yet to be fully realized, as the mechanical properties of MSC-based constructs are lower than those of chondrocyte-based constructs cultured identically. The aim of this study was to better understand the transcriptional underpinnings of this functional limitation. Matched chondrocytes and MSCs from three donors were cultured in agarose in a defined medium containing transforming growth factor β3 (TGF-β3). We evaluated the compressive mechanical properties and matrix deposition of maturing constructs over 56 days. Transcriptional differences between the two cell types were assessed on day 0 and 28 via microarray analysis and real-time polymerase chain reaction; differential deposition of matrix molecules was assessed by immunohistochemistry. Although the mechanical and biochemical properties of cell-seeded constructs improved with culture duration, MSC values plateaued at day 28, and remained lower than chondrocyte values. Using microarray analysis, 324 genes were identified as mis-expressed during chondrogenesis. Differential expression of 18 genes was validated, and differential deposition of proteoglycan 4 and TGF-beta-induced 68 kDa protein (TGFBI) was confirmed. Temporal expression profiles of these 18 genes showed that some genes were never expressed (chondromodulin), some were expressed at lower levels (proteoglycan 4), and some were expressed only at later time points (TGFBI) in MSCs compared to chondrocytes. These findings further define the complex transcriptional topography of MSC chondrogenesis, and provide new benchmarks for optimizing the growth of MSC-based engineered cartilage

Access to drug abuse treatment under Treatment on Demand policy in San Francisco

Objectives: We evaluated whether implementation of Treatment on Demand (TOD) policy in San Francisco was associated with improved access to drug abuse treatment. Methods: Data came from San Francisco's treatment program waiting list over 4 years spanning the implementation of TOD policy. Access measures were monthly applicants waiting and days waited by treatment admissions. Quantitative analyses with 69 treatment facilities contrasted those receiving vs. not receiving TOD funds. Qualitative data came from interviews with facility administrators. Results: There was a small statistically significant decline in monthly waiting lists in the number of people waiting for treatment during the study period. The days waited by those admitted to treatment, however, significantly increased in TOD-funded facilities. Facilities used varied criteria for completing the access measures, which limit the utility of the measures. Conclusions: Access to treatment improved slightly with implementation of TOD policy

Access to drug abuse treatment under Treatment on Demand policy in San Francisco

Objectives: We evaluated whether implementation of Treatment on Demand (TOD) policy in San Francisco was associated with improved access to drug abuse treatment. Methods: Data came from San Francisco's treatment program waiting list over 4 years spanning the implementation of TOD policy. Access measures were monthly applicants waiting and days waited by treatment admissions. Quantitative analyses with 69 treatment facilities contrasted those receiving vs. not receiving TOD funds. Qualitative data came from interviews with facility administrators. Results: There was a small statistically significant decline in monthly waiting lists in the number of people waiting for treatment during the study period. The days waited by those admitted to treatment, however, significantly increased in TOD-funded facilities. Facilities used varied criteria for completing the access measures, which limit the utility of the measures. Conclusions: Access to treatment improved slightly with implementation of TOD policy