Gallotannin from Bouea macrophylla Seed Extract Suppresses Cancer Stem-like Cells and Radiosensitizes Head and Neck Cancer

Cancer stem cells (CSCs) play a critical role in radiation resistance and recurrence. Thus, drugs targeting CSCs can be combined with radiotherapy to improve its antitumor efficacy. Here, we investigated whether a gallotannin extract from Bouea macrophylla seed (MPSE) and its main bioactive compound, pentagalloyl glucose (PGG), could suppress the stemness trait and further confer the radiosensitivity of head and neck squamous cell carcinoma (HNSCC) cell lines. In this study, we evaluate the effect of MPSE or PGG to suppress CSC-like phenotypes and radiosensitization of HNSCC cell lines using a series of in vitro experiments, tumorsphere formation assay, colony formation assay, apoptosis assay, and Western blotting analysis. We demonstrate that MPSE or PGG is able to suppress tumorsphere formation and decrease protein expression of cancer stem cell markers. MPSE or PGG also enhanced the radiosensitivity in HNSCC cells. Pretreatment of cells with MPSE or PGG increased IR-induced DNA damage (γ-H2Ax) and enhanced radiation-induced cell death. Notably, we observed that pretreatment with MPSE or PGG attenuated the IR-induced stemness-like properties characterized by tumorsphere formation and the CD44 CSC marker. Our findings describe a novel strategy for increasing therapeutic efficacy for head and neck cancer patients using the natural products MPSE and PGG.     

Iron–Quercetin Complex Preconditioning of Human Peripheral Blood Mononuclear Cells Accelerates Angiogenic and Fibroblast Migration: Implications for Wound Healing

Cell-based therapy is a highly promising treatment paradigm in ischemic disease due to its ability to repair tissue when implanted into a damaged site. These therapeutic effects involve a strong paracrine component resulting from the high levels of bioactive molecules secreted in response to the local microenvironment. Therefore, the secreted therapeutic can be modulated by preconditioning the cells during in vitro culturing. Herein, we investigated the potential use of magnetic resonance imaging (MRI) probes, the “iron–quercetin complex” or IronQ, for preconditioning peripheral blood mononuclear cells (PBMCs) to expand proangiogenic cells and enhance their secreted therapeutic factors. PBMCs obtained from healthy donor blood were cultured in the presence of the iron–quercetin complex. Differentiated preconditioning PBMCs were characterized by immunostaining. An enzyme-linked immunosorbent assay was carried out to describe the secreted cytokines. In vitro migration and tubular formation using human umbilical vein endothelial cells (HUVECs) were completed to investigate the proangiogenic efficacy. IronQ significantly increased mononuclear progenitor cell proliferation and differentiation into spindle-shape-like cells, expressing both hematopoietic and stromal cell markers. The expansion increased the number of colony-forming units (CFU-Hill). The conditioned medium obtained from IronQ-treated PBMCs contained high levels of interleukin 8 (IL-8), IL-10, urokinase-type-plasminogen-activator (uPA), matrix metalloproteinases-9 (MMP-9), and tumor necrosis factor-alpha (TNF-α), as well as augmented migration and capillary network formation of HUVECs and fibroblast cells, in vitro. Our study demonstrated that the IronQ-preconditioning PBMC protocol could enhance the angiogenic and reparative potential of non-mobilized PBMCs. This protocol might be used as an adjunctive strategy to improve the efficacy of cell therapy when using PBMCs for ischemic diseases and chronic wounds. However, in vivo assessment is required for further validation.     

Cytokine Profiling and Intra-Articular Injection of Autologous Platelet-Rich Plasma in Knee Osteoarthritis

Osteoarthritis (OA) is a degenerative joint disease leading to joint pain and stiffness. Due to lack of effective treatments, physical and psychological disabilities caused by OA have a detrimental impact on the patient’s quality of life. Emerging evidence suggests that intra-articular injection of platelet-rich plasma (PRP) may provide favorable results since PRP comprises not only a high level of platelets but also a huge amount of cytokines, chemokines, and growth factors. However, the precise mechanism and standardization method remain uncertain. This study aimed to examine cytokine profiling in both PRP and platelet-poor plasma (PPP) of knee OA patients and to determine the effects of PRP on OA chondrocytes and knee OA patients. PRP contained a wide variety of cytokines, chemokines, growth factors, and autologous intra-articular PRP injection resulted in favorable outcomes in knee OA patients. Significant increases in levels of IL-1, IL-2, IL-7, IL-8, IL-9, IL-12, TNF-α, IL-17, PDGF-BB, bFGF, and MIP-1β were detected in PRP compared to PPP (p < 0.001). An in vitro study showed a marked increase in proliferation in OA chondrocytes cultured with PRP, compared to PPP and fetal bovine serum (p < 0.001). In a clinical study, knee OA patients treated with PRP showed improvement of physical function and pain, assessed by physical performance, Western Ontario and McMaster Universities Arthritis Index and visual analog scale. Our findings from both in vitro and clinical studies suggest that intra-articular PRP injection in knee OA patients may be a potential therapeutic strategy for alleviating knee pain and delaying the need for surgery.