Bioengineering & Translational Medicine最新文献

We describe the use of ultrasound image guidance to improve treatment outcomes when administering interstitial photothermal therapy (I-PTT), an experimental cancer treatment modality. I-PTT is a promising thermal therapy for tumors using intratumorally injected nanoparticle-based photothermal agents activated by an interstitially placed laser diffuser. We hypothesized that ultrasound-based image guidance yields improved tumor treatment outcomes in terms of tumor regression and survival by improving the accuracy of the placement of the laser fiber and nanoparticles within a tumor and facilitating more precise PTT delivery. To test this hypothesis, we assessed the effect of ultrasound-guided I-PTT (US I-PTT) on neuroblastoma, an aggressive solid tumor of childhood, using the 9464D syngeneic model in C57BL/6 mice. US I-PTT using Prussian blue nanoparticles activated by an interstitial cylindrical laser diffuser generated an equivalent in vivo thermal dose as blinded, non-image-guided I-PTT (B I-PTT). However, US I-PTT resulted in significantly higher treatment accuracy compared to B I-PTT, attributable to the image guidance. Importantly, this improved accuracy translated to improved treatment outcomes wherein mice treated with US I-PTT exhibited significantly improved tumor regression, tumor-free survival, and long-term survival compared to mice treated with B I-PTT. Further, histological analyses of the tumors post-PTT confirmed the advantages conferred by US I-PTT over B I-PTT for tumor control. These proof-of-concept results demonstrate the value of using ultrasound guidance for I-PTT treatment and the translational implications of this approach to provide a more accurate and effective treatment for neuroblastoma.

Recent studies show that tumor cells undergo apoptosis after mechanical stretching, which promotes normal cell growth. Since ultrasound can produce similar sub-cellular mechanical stresses on the nanoscale, here we test the effect of ultrasound-mediated mechanical forces on tumors and normal cell survival. Surprisingly, tumor cells undergo apoptosis through a calpain-dependent mitochondrial pathway that relies upon calcium entry through the mechanosensitive Piezo1 channels. This is a general property of all tumor cell lines tested irrespective of tissue origin, but normal cells are unaffected. In vivo, ultrasound treatment promotes tumor cell killing in a mouse model with invasive CT26 cancer cell subcutaneous tumors and in the chick chorioallantoic membrane (CAM) model with relatively minor damage to chick embryos. Further, patient-derived pancreatic tumor organoids are killed by ultrasound treatment. Because ultrasound-mediated mechanical forces cause apoptosis of tumor cells from many different tissues in different microenvironments, it may offer a safe, non-invasive approach to augment tumor treatments.

With papillary thyroid carcinoma (PTC) rates rising significantly, concerns about conventional treatments like thyroidectomy and radiotherapy highlight the need for non-invasive options. Our study explores photobiomodulation therapy (PBMT), which uses specific light wavelengths to evoke cellular responses in PTC treatment. Our research utilized a custom-designed optical system to investigate PBMT, finding that blue light at a wavelength of 465 nm can safely and effectively inhibit the proliferation of the TPC-1 PTC cell line by inducing cell cycle arrest. Additionally, we developed a wirelessly powered wearable PBMT device, which is equipped with an advanced light delivery system that ensures precise and consistent dosage. This device designed for optimal patient comfort, effectively suppressed tumor growth in mouse models without adverse effects. PBMT indicates thyroid tissue's light responsiveness as a non-visual organ. Our study's innovative approach integrates the disciplines of oncology, biophysics, and medical device technology, thereby advancing the treatment paradigms for PTC. This interdisciplinary bridge not only highlights our groundbreaking findings but also paves the way for future research in cancer therapy and photomedicine.

Air pollution is an exogenous stressor known to have a detrimental impact on skin health through the induction of inflammation; however, the direct effect of topical pollution exposure is still being elucidated. Human skin equivalents (HSE) aim to reproduce in vitro the structure and function of the native skin tissue. However, HSEs typically lack skin-resident immune cells, which could play a key role in the inflammatory response induced by pollution exposure. We outline the development of a HSE-containing MUTZ-3-derived Langerhans cells (MUTZ-3-LCs), which show dendritic morphology and Langerhans cell marker expression. We demonstrated that HSE-containing MUTZ-3-LC have lower basal levels of proinflammatory cytokines, but topical stimulation with allergens and irritant compounds induced a greater inflammatory response in these models compared to HSE without immune cells. To study the effect of pollution, we created a technique to apply diesel particulate matter (DPM) to HSEs. Though our microscopic analysis demonstrated that DPM does not penetrate the stratum corneum, we showed that DPM did induce production of proinflammatory cytokines, but notably only in HSEs containing MUTZ-3-LCs. These data suggest that topical exposure to air pollution can induce cutaneous inflammation and that skin-resident immune cells contribute to this response. This highlights the significance of immune-competent HSEs to the study of exogenous stressors in vitro.

Reduced glutathione (GSH) could reduce oxidative stress to improve adipose tissue-derived mesenchymal stem cell (ADSC) engraftment efficiency in vivo. However, the underlying mechanisms remain unclear. Our goal is to investigate whether GSH enhances ADSC engraftment through targeting the TGFβ/SMAD3/NOX4 pathway. Liver fibrotic male mice were administrated GSH, setanaxib (STX), and SIS3 during ADSC transplantation. ADSC engraftment efficiency and reactive oxygen species (ROS) level were detected both in vivo and ex vivo. Biochemical analysis was used to analyze the content of superoxide and nicotinamide adenine dinucleotide phosphate oxidases (NOXs) in liver tissues. Immunohistochemistry and western blotting were used to examine the protein level of NOX1, NOX2, NOX4, transforming growth factor-β1 (TGFβ1), SMAD3, and p-SMAD3 in liver tissues. Additionally, the therapeutic efficacy of the ADSC transplantation was further investigated. We found that GSH significantly improved ADSC engraftment efficiency, which was closely related to the reduced ROS generation in liver tissues. However, the enhanced cell engraftment was abolished after the combined treatment with STX or SIS3. GSH could effectively reduce superoxide and NOXs content, and selectively inhibit NOX4 expression in liver tissues. The co-localization results showed that GSH could reduce NOX4 expressed in activated hepatic stellate cells. Mechanistically, GSH down-regulated TGFβ/SMAD3 signaling. More importantly, GSH enhanced the therapeutic efficacy of ADSC therapy in liver fibrotic mice. Taken together, GSH could improve the engraftment efficiency of ADSCs in liver fibrosis by targeting TGFβ1/SMAD3/NOX4 signaling pathway, which provides a new theoretical basis for GSH enhancing ADSC engraftment efficiency in liver diseases.