Low Molecular Weight Fraction of Commercial Human Serum Albumin Induces Morphologic and Transcriptional Changes of Bone Marrow-Derived Mesenchymal Stem Cells.

Osteoarthritis (OA) is the most common chronic disease of the joint; however, the therapeutic options for severe OA are limited. The low molecular weight fraction of commercial 5% human serum albumin (LMWF5A) has been shown to have anti-inflammatory properties that are mediated, in part, by a diketopiperazine that is present in the albumin preparation and that was demonstrated to be safe and effective in reducing pain and improving function when administered intra-articularly in a phase III clinical trial. In the present study, bone marrow-derived mesenchymal stem cells (BMMSCs) exposed to LMWF5A exhibited an elongated phenotype with diffuse intracellular F-actin, pronounced migratory leading edges, and filopodia-like projections. In addition, LMWF5A promoted chondrogenic condensation in "micromass" culture, concurrent with the upregulation of collagen 2α1 mRNA. Furthermore, the transcription of the CXCR4-CXCL12 axis was significantly regulated in a manner conducive to migration and homing. Several transcription factors involved in stem cell differentiation were also found to bind oligonucleotide response element probes following exposure to LMWF5A. Finally, a rapid increase in PRAS40 phosphorylation was observed following treatment, potentially resulting in the activation mTORC1. Proteomic analysis of synovial fluid taken from a preliminary set of patients indicated that at 12 weeks following administration of LMWF5A, a microenvironment exists in the knee conducive to stem cell infiltration, self-renewal, and differentiation, in addition to indications of remodeling with a reduction in inflammation. Taken together, these findings imply that LMWF5A treatment may prime stem cells for both mobilization and chondrogenic differentiation, potentially explaining some of the beneficial effects achieved in clinical trials.

New approaches to prophylactic human papillomavirus vaccines for cervical cancer prevention.

The currently licensed human papillomavirus (HPV) vaccines are safe and highly effective at preventing HPV infection for a select number of papillomavirus types, thus decreasing the incidence of precursors to cervical cancer. It is expected that vaccination will also ultimately reduce the incidence of this cancer. The licensed HPV vaccines are, however, type restricted and expensive, and also require refrigeration, multiple doses and intramuscular injection. Second-generation vaccines are currently being developed to address these shortcomings. New expression systems, viral and bacterial vectors for HPV L1 capsid protein delivery, and use of the HPV L2 capsid protein will hopefully aid in decreasing cost and increasing ease of use and breadth of protection. These second-generation vaccines could also allow affordable immunization of women in developing countries, where the incidence of cervical cancer is high.