Purpose: The topical application of exosomes secreted by mesenchymal stem cells (MSC-Exos) on the skin is a very new and interesting topic in the medical field. In this study, we aimed to investigate whether marine sponge Haliclona sp. spicules (SHSs) could effectively enhance the skin delivery of human umbilical cord-derived MSC-Exos (hucMSC-Exos), and further evaluate the topical application of hucMSC-Exos combined with SHSs in rejuvenating photoaged mouse skin. Materials and Methods: SHSs were isolated from the explants of sponge Haliclona sp. with our proprietary method, and hucMSC-Exos were prepared from the conditioned medium of hucMSCs using ultracentrifugation. The effects of SHSs on the skin penetration of fluorescently labeled hucMSC-Exos were determined using confocal microscopy in vitro (porcine skin) and in vivo (mouse skin). The therapeutic effects of hucMSC-Exos coupled with SHSs against UV-induced photoaging in mice were assessed by using microwrinkles analysis, pathohistological examination and real-time RT-PCR. We also tested the skin irritation caused by the combination of hucMSC-Exos and SHSs in guinea pigs. Results: In vitro results showed that hucMSC-Exos could not readily penetrate through porcine skin by themselves. However, SHSs increased the skin absorption of exosomes by a factor of 5.87 through creating microchannels. Similar penetration enhancement of hucMSC-Exos was observed after SHSs treatment in mice. The combined use of hucMSC-Exos and SHSs showed significant anti-photoaging effects in mice, including reducing microwrinkles, alleviating histopathological changes, and promoting the expression of extracellular matrix constituents, whereas hucMSC-Exos alone produced considerably weaker effects. Skin irritation test showed that the combination of hucMSC-Exos and SHSs caused slight irritation, and the skin recovered shortly. Conclusion: SHSs provide a safe and effective way to enhance the skin delivery of MSC-Exos. Moreover, the combination of MSC-Exos and SHSs may be of much use in the treatment of photoaging.

Lung cancer is the leading cause of cancer mortality worldwide. Dendritic cells (DCs) are the key factors providing protective immunity against lung tumors and clinical trials have proven that DC function is reduced in lung cancer patients. It is evident that the immunoregulatory network may play a key role in the failure of the immune response to terminate tumors. Lung tumors likely employ numerous strategies to suppress DC‐based anti‐tumor immunity. Here, we summarize the recent advances in our understanding on lung tumor‐induced immunosuppression in DCs, which affects the initiation and development of T‐cell responses. We also describe which existing measures to restore DC function may be useful for clinical treatment of lung tumors. Furthering our knowledge of how lung cancer cells alter DC function to generate a tumor‐supportive environment will be essential in order to guide the design of new immunotherapy strategies for clinical use.

Tumor extracellular matrix (ECM) not only forms a physical barrier for T cells infiltration, but also regulates multiple immunosuppressive pathways, which is an important reason for immunotherapy failure. The cyclic guanosine monophosphate‐adenosine monophosphate synthase‐stimulator of interferon genes (cGAS‐STING) pathway plays a key role in activating CD8⁺ T cells, maintaining CD8⁺ T cells stemness and enhancing the antitumor effect. Herein, a zinc‐organometallic framework vaccine (ZPM@OVA‐CpG) prepared by self‐assembly, which achieves site‐directed release of Zn²⁺ in dendritic cell (DC) lysosomes and tumor microenvironment under acidic conditions, is reported. The vaccine actively targets DC, significantly enhances cGAS‐STING signal, promotes DC maturation and antigen cross‐presentation, and induces strong activation of CD8⁺ T cells. Meanwhile, the vaccine reaches the tumor site, releasing Zn²⁺, significantly up‐regulates the activity of matrix metalloproteinase‐2, degrades various collagen components of tumor ECM, effectively alleviates immune suppression, and significantly enhances the tumor infiltration and killing of CD8⁺ T cells. ZPM@OVA‐CpG vaccine not only solves the problem of low antigen delivery efficiency and weak CD8⁺ T cells activation ability, but also achieves the degradation of tumor ECM via the vaccine for the first time, providing a promising therapeutic platform for the development of efficient novel tumor vaccines.

Allogeneic pancreatic islet transplantation theoretically represents a cure for type 1 diabetes. However, current immune suppressive therapies are often associated with undesired side effects. Given this problem, and the shortage of human islet donors, the majority of type 1 diabetes patients cannot currently be offered an islet transplant. However, it has been found that mesenchymal stem cells (MSCs) could exert unique immunosuppressive effects both in vitro and in vivo. Herein we transplanted allogeneic 200 islets alone or in combination with MSCs (3 × 10⁶ cells) under the kidney capsules of diabetic C57LB/6 mouse. We found that the ratios of T helper type 1 (Th1) to Th2 and Tc1 to Tc2 were reduced, and the numbers of naive and memory T cells were down-regulated in peripheral blood after transplantation. In addition, the maturation, endocytosis and interleukin-12 secretion of dendritic cell (DCs)-derived bone marrow cells (BMCs) from receptor mice were suppressed. Rejection reaction was alleviated by MSCs which exerted suppressive effects through T lymphocyte subsets and DCs.