Infrapatellar fat pad-derived mesenchymal stromal cell product for treatment of knee osteoarthritis: a first-in-human study with evaluation of the potency marker.

BACKGROUND AIMS: Infrapatellar fat pad-derived mesenchymal stromal cells (IFP-MSCs) have not yet been used in a human clinical trial. In this open-label phase 1 study, patients with knee osteoarthritis (OA) received a single intra-articular injection of autologous IFP-MSCs. Safety was assessed through physical examination of the knee joint, vital signs, laboratory tests and adverse events. Efficacy was evaluated with regard to pain and function using questionnaires, x-ray and magnetic resonance imaging (MRI). Indoleamine-2,3-dioxygenase (IDO) expression in IFP-MSCs primed with interferon gamma was used as an in vitro potency measurement in investigating the correlations of clinical outcomes. METHODS: Twelve patients with symptomatic knee OA were recruited. IFP adipose tissue was harvested from each patient's knee through surgical excision for IFP-MSC manufacturing. Cryopreserved IFP-MSCs (5 × 107 cells) were injected into the knee joint immediately after thawing. RESULTS: No significant adverse events were observed. Patients who received IFP-MSCs exhibited clinically significant pain and functional improvement at 48-week follow-up. The MRI Osteoarthritis Knee Score average was also significantly reduced from 100.2 before injection to 85.0 at 48 weeks after injection. The IDO expression of the primed IFP-MSCs of the 12 patients was correlated with clinical outcomes after injection. CONCLUSIONS: A single intra-articular injection of IFP-MSCs appears to be a safe therapy for treating knee OA and may improve disease symptoms. IDO measurement of primed IFP-MSCs has potential as a potency marker of MSC products for immunomodulatory therapy.

A comparative study of the interaction of Bartonella henselae strains with human endothelial cells.

Bartonella henselae can cause a wide range of clinical outcomes and may lead to severe disease, especially in patients with acquired immunodeficiency syndrome. It is well-known that B. henselae-induced cell proliferation is mediated by anti-apoptotic activity; however, the detailed mechanism is still unclear. In this study, the cellular responses of endothelial cells after infection with four B. henselae strains were compared and protein candidates that may be involved in the interaction between cells and bacteria were determined. The Houston-1 strain elicited the fastest response in terms of stimulating endothelial cell proliferation, and the JK-40 strain had the strongest ability to induce cell proliferation. By Western blot analysis, it was demonstrated that B. henselae-induced cell proliferation involved the mitochondria intrinsic apoptotic pathway. In addition, the adhesion abilities of the U-4 and JK-40 strains were much greater than those of the Houston-1 and JK-47 strains; however, the ability of Houston-1 to invade host cells was high. By two-dimensional gel electrophoresis analysis, it was found that succinyl-CoA synthetase subunit beta, phage-related protein, and ATP synthase subunit alpha might be involved in the invasion process. The expression of superoxide dismutase [Cu-Zn] precursor increased with infection time for all four strains but was significantly higher in the Houston-1 strain, which may increase the competitive advantage of Houston-1 in terms of survival in host cells and render it successful in invading host cells and stimulating cell proliferation. Our data suggest that the interaction of B. henselae and endothelial cells differed between strains, and the results indicated possible candidate proteins that may play a role in the pathogenesis of B. henselae infection.

Increased prevalence of interleukin-17-producing CD4(+) tumor infiltrating lymphocytes in human oral squamous cell carcinoma.

BACKGROUND: T helper 17 (Th17) and regulatory T cells share plasticity in the expression of interleukin (IL)-17 and forkhead box P3 (FOXP3), but their mutual presence in human diseases is unclear. METHODS: IL-17 and FOXP3 were analyzed by immunohistostaining and flow cytometry. The cytokine milieu was analyzed by quantitative reverse transcriptase-polymerase chain reaction (RT-PCR). RESULTS: Oral squamous cell carcinoma expresses high levels of IL-1ß, IL-6, and transforming growth factor (TGF)-ß. A unique subset of FOXP3(+) IL-17-producing CD4(+) T cells was consistently identified in tumor-infiltrating lymphocytes from advanced stages of cancer, but not in the circulation, at a frequency of 0.5% to 5.5 % of total CD4(+) T and positively correlated with the frequency of IL-17(+)FOXP3(-) T cells. The IL-17(+)FOXP3(+) T cells express CCR6 and suppress the proliferation of autologous CD4(+) CD25(-) responder T-cells in vitro. CONCLUSIONS: The prevalence of IL-17-producing FOXP3(+) CD4(+) tumor infiltrating lymphocytes is increased in oral squamous cell carcinoma.