Bioengineering & Translational Medicine最新文献

The endometrium, the inner lining of the uterus, assumes a crucial role in the female reproductive system. Disorders and injuries impacting the endometrium can lead to profound consequences, including infertility and compromised women's overall health. Recent advancements in stem cell research have opened new possibilities for the treatment and repair of endometrial issues. In the present study, we constructed a degradable hydrogel by loading adipose-derived stem cells (ADSCs) and melanin nanoparticles (MNP). In vitro cell experiments validated the biocompatibility of the prepared hydrogels and their adeptness in encapsulating ADSCs. Subsequently, we explored the impact of hydrogel@ADSC@MNP constructs in the healing process of uterine injury in mice. The results indicated that hydrogel@ADSC@MNP could augment endometrial thickness and ameliorate endometrial interstitial fibrosis. The injured tissue adjacent to hydrogel@ADSC@MNP constructs exhibited higher levels of bFGF, IGF-1, and VEGFA compared with the corresponding tissue in mice receiving hydrogel constructs alone or in the model group. Furthermore, the hydrogel@ADSC@MNP system enhanced the proliferative capabilities of uterine endometrial cells, facilitated microvasculature regeneration, and reinstated the endometrium's capacity to receive the embryos. Our findings strongly suggest that the hydrogel@ADSC@MNP system holds significant promise for repairing and regenerating damaged endometrium.

Messenger RNA (mRNA) has emerged as a promising therapeutic strategy for various diseases, including cancer, infectious diseases, and genetic disorders. The mRNA-based therapeutics have gained significant attention due to their ability to regulate targeted cells, activate immune cells, and avoid potential risks associated with DNA-based technology. However, the clinical application of mRNA in cancer therapy is hindered by the instability of RNA, physiological barriers, and the risk of immunogenic hurdles. To overcome these challenges and ensure the safe delivery of mRNA therapeutics to target sites, nanoparticle-based delivery systems have been explored as potential tools in vitro and in vivo applications. This review provides a comprehensive overview of the current status of mRNA therapy, discussing its advantages and limitations, delivery strategies and materials, as well as applications in different fields. By exploring these aspects, the researcher can gain a more complete understanding of the current state, prospects, and challenges of mRNA technologies.

Chao Deng, Qiong Liu, Huadong Zhao, Lu Qian, Wagnrui Lei, Wenwen Yang, Zhenxing Liang, Ye Tian, Shaofei Zhang, Changyu Wang, Ying Chen, Yang Yang. Activation of NR1H3 attenuates the severity of septic myocardial injury by inhibiting NLRP3 inflammasome. Bioeng Transl Med. 2023; 8(3):e10517.

An inaccuracy has been found in the statistical graph of ABCA1 in Figure 2c of the published article. The corrected version of Figure 2 is shown below.

We apologize for this error.

The major histocompatibility complex class I (MHCI) trafficking signal (MITD) plays a pivotal role in enhancing the efficacy of mRNA vaccines. However, there was a lack of research investigating its efficacy in enhancing immune responses to RNA virus infections. Here, we have developed an innovative strategy for the formulation of mRNA vaccines. This approach involved the integration of MITD into the mRNA sequence encoding the virus antigen. Mechanistically, MITD-based mRNA vaccines can strengthen immune protection by mimicking the dynamic trafficking properties of MHCI molecule and thus expand the memory specific B and T cells. The model MITD-based mRNA vaccines encoding binding receptor-binding domain (RBD) of SARS-CoV-2 were indeed found to achieve protective duration, optimal storage stability, broad efficacy, and high safety.

Cell therapies are at the forefront of novel therapeutics. Neutrophils, despite being the most populous immune cells in human blood circulation, are not considered a viable option for cellular therapies because of their short lifespan and poor understanding of their role in the pathophysiology of various diseases. In inflammatory conditions, neutrophils exhibit an activated phenotype. Activation brings about significant changes to neutrophil biology such as increased lifespan, inflammatory cytokine secretion, and enhanced effector functions. Activated neutrophils also possess the potential to stimulate the downstream immune response and are described as essential effectors in the immune response to tumors. This makes activated neutrophils an interesting candidate for cell therapies. Here, we review the biology of activated neutrophils in detail. We discuss the different ways neutrophils can be activated and the effect they have on other immune cells for stimulation of downstream immune response. We review the conditions where activated neutrophil therapy can be therapeutically beneficial and discuss the challenges associated with their eventual translation. Overall, this review summarizes the current state of understanding of neutrophil-based immunotherapies and their clinical potential.

Immune checkpoint inhibitors (ICIs) represent new therapeutic candidates against glioblastoma multiforme (GBM); however, their efficacy is clinically limited due to both local and systemic immunosuppressive environments. Hence, therapeutic approaches that stimulate local and systemic immune environments can improve the efficacy of ICIs. Here, we report an adoptive cell therapy employing neutrophils (NE) that are activated via surface attachment of drug-free disk-shaped backpacks, termed Cyto-Adhesive Micro-Patches (CAMPs) for treating GBM. CAMP-adhered neutrophils (NE/CAMPs) significantly improved the efficacy of an anti-PD1 antibody (aPD-1) in a subcutaneous murine GBM model (GL261). A combination of NE/CAMPs and aPD-1 completely regressed subcutaneous GL261 tumors in mice. The efficacy of NE/CAMPs against GBM was also tested in an orthotopic GL261 model. Neutrophil's ability to migrate into the brain was not affected by CAMP attachment, and intracerebral NE/CAMP accumulation was observed in mice-bearing orthotopic GBM. The combination treatment of NE/CAMPs and aPD-1 activated systemic immune responses mediated by T cells and showed improved therapeutic responses compared with aPD-1 alone in the orthotopic GBM model. These results suggest that immunomodulation with NE/CAMPs offers a potential approach for the treatment of GBM by combination with ICIs.

Diabetic wounds present a significant challenge in regenerative medicine due to impaired healing, characterized by prolonged inflammation and deficient tissue repair, primarily caused by a skewed pro-inflammatory macrophage phenotype. This study investigates the therapeutic potential of interleukin-10 (IL-10) chemically modified mRNA (modRNA)-enriched human adipose-derived multipotent stromal cells (hADSCs) in a well-established murine model of diabetic wounds. The modRNAs used in this study were chemically modified using N1-methylpseudouridine-5′-triphosphate (m1Ψ) by substituting uridine-5-triphosphate. In vitro experiments demonstrated that IL-10 modRNA-transfected hADSCs effectively modulated macrophage polarization towards an anti-inflammatory phenotype. In vivo experiments with a well-established murine model demonstrated that transplantation of hADSCs^modIL-10 on postoperative day 5 (POD5) significantly improved wound healing outcomes, including accelerated wound closure, enhanced re-epithelialization, promoted M2 polarization, improved collagen deposition, and increased neovascularization. This study concludes that IL-10 modRNA-enriched hADSCs offer a promising therapeutic approach for diabetic wound healing, with the timing of IL-10 administration playing a crucial role in its effectiveness. These cells modulate macrophage polarization and promote tissue repair, demonstrating their potential for improving the management of diabetic wounds.

This study presents a novel in vitro bilayer 3D co-culture platform designed to obtain cancer-associated fibroblasts (CAFs)-like cells. The platform consists of a bilayer hydrogel structure with a collagen/polyethylene glycol (PEG) hydrogel for fibroblasts as the upper layer and an alginate hydrogel for tumor cells as the lower layer. The platform enabled paracrine interactions between fibroblasts and cancer cells, which allowed for selective retrieval of activated fibroblasts through collagenase treatment for further study. Fibroblasts remained viable throughout the culture periods and showed enhanced proliferation when co-cultured with cancer cells. Morphological changes in the co-cultured fibroblasts resembling CAFs were observed, especially in the 3D microenvironment. The mRNA expression levels of CAF-related markers were significantly upregulated in 3D, but not in 2D co-culture. Proteomic analysis identified upregulated proteins associated with CAFs, further confirming the transformation of normal fibroblasts into CAF within the proposed 3D co-culture platform. Moreover, co-culture with CAF induced radio- and chemoresistance in pancreatic cancer cells (PANC-1). Survival rate of cancer cells post-irradiation and gemcitabine resistance increased significantly in the co-culture setting, highlighting the role of CAFs in promoting cancer cell survival and therapeutic resistance. These findings would contribute to understanding molecular and phenotypic changes associated with CAF activation and provide insights into potential therapeutic strategies targeting the tumor microenvironment.

Osteoarthritis (OA) is a degenerative joint disease that affects the entire joint and has been a huge burden on the health care system worldwide. Although traditional therapy and targeted cartilage cell therapy have made significant progress in the treatment of OA and cartilage regeneration, there are still many problems. Mesenchymal stem cells from various tissues are the most studied cell type and have been used in preclinical and clinical studies of OA, because they are more widely available, have a greater capacity for in vitro expansion, and have anti-inflammatory and immunomodulatory properties compared to autologous chondrocytes. This article will systematically review the latest developments in these areas. It may provide new insights for improving OA and cartilage regeneration.

Sperm quality analysis plays an important role in diagnosing infertility, which is widely implemented by computer-assisted sperm analysis (CASA) of sperm-swimming imaging from commercial phase-contrast microscopy. A well-equipped microscope comes with a high cost, increasing the burden of assessment, and it also occupies a large volume. For point-of-care testing (POCT) of sperm quality, these factors are confronted with the challenges of low-cost and portable instruments. In this study, an encoded light-emitting diode (LED) array illumination is employed to achieve a portable microscope with multicontrast imaging for sperm quality analysis. This microscopy has dimensions of 16.5 × 14.0 × 25.0 cm, and its dark-field (DF) imaging provides high-contrast sperm image data which is suitable for CASA. According to DF imaging, we developed a software of LabCASA, which can used to assess the motility characteristics of sperm. Compared with TrackMate, the difference in motility parameters from our software was less than 10% in the coefficient of variation (CV). The sperm motility parameters vary with the chamber temperature, which further confirms the reliability of our system with DF imaging. The DF imaging provides strong robustness for tracking sperm's motion under different microscopes. For assessment of the motility parameters, our system can work at a lower cost with a plastic structure. This system with DF imaging is suitable for portable POCT of sperm quality analysis, which is highly cost-effective in resource-constrained circumstances.