@article{wang_popowski_zhu_abad_wang_liu_lutz_de naeyer_demarco_denny_et al._2022, title={Exosomes decorated with a recombinant SARS-CoV-2 receptor-binding domain as an inhalable COVID-19 vaccine}, volume={7}, ISSN={["2157-846X"]}, url={https://doi.org/10.1038/s41551-022-00902-5}, DOI={10.1038/s41551-022-00902-5}, abstractNote={The first two mRNA vaccines against infection by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) that were approved by regulators require a cold chain and were designed to elicit systemic immunity via intramuscular injection. Here we report the design and preclinical testing of an inhalable virus-like-particle as a COVID-19 vaccine that, after lyophilisation, is stable at room temperature for over three months. The vaccine consists of a recombinant SARS-CoV-2 receptor-binding domain (RBD) conjugated to lung-derived exosomes which, with respect to liposomes, enhance the retention of the RBD in both the mucus-lined respiratory airway and in lung parenchyma. In mice, the vaccine elicited RBD-specific IgG antibodies, mucosal IgA responses and CD4+ and CD8+ T cells with a Th1-like cytokine expression profile in the animals' lungs, and cleared them of SARS-CoV-2 pseudovirus after a challenge. In hamsters, two doses of the vaccine attenuated severe pneumonia and reduced inflammatory infiltrates after a challenge with live SARS-CoV-2. Inhalable and room-temperature-stable virus-like particles may become promising vaccine candidates.}, journal={NATURE BIOMEDICAL ENGINEERING}, author={Wang, Zhenzhen and Popowski, Kristen D. and Zhu, Dashuai and Abad, Blanca Lopez de Juan and Wang, Xianyun and Liu, Mengrui and Lutz, Halle and De Naeyer, Nicole and DeMarco, C. Todd and Denny, Thomas N. and et al.}, year={2022}, month={Jul} }
 @article{popowski_moatti_scull_silkstone_lutz_lópez de juan abad_george_belcher_zhu_mei_et al._2022, title={Inhalable dry powder mRNA vaccines based on extracellular vesicles}, volume={5}, ISSN={2590-2385}, url={http://dx.doi.org/10.1016/j.matt.2022.06.012}, DOI={10.1016/j.matt.2022.06.012}, abstractNote={Respiratory diseases are a global burden, with millions of deaths attributed to pulmonary illnesses and dysfunctions. Therapeutics have been developed, but they present major limitations regarding pulmonary bioavailability and product stability. To circumvent such limitations, we developed room-temperature-stable inhalable lung-derived extracellular vesicles or exosomes (Lung-Exos) as mRNA and protein drug carriers. Compared with standard synthetic nanoparticle liposomes (Lipos), Lung-Exos exhibited superior distribution to the bronchioles and parenchyma and are deliverable to the lungs of rodents and nonhuman primates (NHPs) by dry powder inhalation. In a vaccine application, severe acute respiratory coronavirus 2 (SARS-CoV-2) spike (S) protein encoding mRNA-loaded Lung-Exos (S-Exos) elicited greater immunoglobulin G (IgG) and secretory IgA (SIgA) responses than its loaded liposome (S-Lipo) counterpart. Importantly, S-Exos remained functional at room-temperature storage for one month. Our results suggest that extracellular vesicles can serve as an inhaled mRNA drug-delivery system that is superior to synthetic liposomes.}, number={9}, journal={Matter}, publisher={Elsevier BV}, author={Popowski, Kristen D. and Moatti, Adele and Scull, Grant and Silkstone, Dylan and Lutz, Halle and López de Juan Abad, Blanca and George, Arianna and Belcher, Elizabeth and Zhu, Dashuai and Mei, Xuan and et al.}, year={2022}, month={Sep}, pages={2960–2974} }
 @article{zhang_zhu_li_huang_hu_lutz_xie_mei_li_neal-perry_et al._2021, title={A stem cell-derived ovarian regenerative patch restores ovarian function and rescues fertility in rats with primary ovarian insufficiency}, volume={11}, ISSN={["1838-7640"]}, url={http://www.scopus.com/inward/record.url?eid=2-s2.0-85114771196&partnerID=MN8TOARS}, DOI={10.7150/thno.61690}, abstractNote={Rationale: Primary ovarian insufficiency (POI) normally occurs before age 40 and is associated with infertility. Hormone replacement therapy is often prescribed to treat vasomotor symptom, but it cannot restore ovarian function or fertility. Stem cell therapy has been studied for the treatment of POI. However, the application of live stem cells has suffered from drawbacks, such as low cell retention/engraftment rate, risks for tumorigenicity and immunogenicity, and lack of off-the-shelf feasibility. Methods: We developed a therapeutic ovarian regenerative patch (ORP) that composed of clinically relevant hydrolysable scaffolds and synthetic mesenchymal stem cells (synMSCs), which are microparticles encapsulating the secretome from MSCs. The therapeutic potency of ORP was tested in rats with cisplatin induced POI injury. Results:In vitro studies revealed that ORP stimulated proliferation of ovarian somatic cells (OSCs) and inhibited apoptosis under injury stress. In a rat model of POI, implantation of ORP rescued fertility by restoring sexual hormone secretion, estrus cycle duration, and follicle development. Conclusion: ORP represents a cell-free, off-the-shelf, and clinically feasible treatment for POI.}, number={18}, journal={THERANOSTICS}, author={Zhang, Sichen and Zhu, Dashuai and Li, Zhenhua and Huang, Ke and Hu, Shiqi and Lutz, Halle and Xie, Mengjie and Mei, Xuan and Li, Junlang and Neal-Perry, Genevieve and et al.}, year={2021}, pages={8894–8908} }
 @misc{popowski_dinh_george_lutz_cheng_2021, title={Exosome therapeutics for COVID-19 and respiratory viruses}, volume={2}, ISSN={["2688-268X"]}, url={https://doi.org/10.1002/VIW.20200186}, DOI={10.1002/VIW.20200186}, abstractNote={Respiratory viral diseases are a leading cause of mortality in humans. They have proven to drive pandemic risk due to their complex transmission factors and viral evolution. However, the slow production of effective antiviral drugs and vaccines allows for outbreaks of these diseases, emphasizing a critical need for refined antiviral therapeutics. The delivery of exosomes, a naturally secreted extracellular vesicle, yields therapeutic effects for a variety of diseases, including viral infection. Exosomes and viruses utilize similar endosomal sorting pathways and mechanisms, providing exosomes with the potential to serve as a therapeutic that can target, bind, and suppress cellular uptake of various viruses including the novel severe acute respiratory syndrome coronavirus 2. Here, we review the relationship between exosomes and respiratory viruses, describe potential exosome therapeutics for viral infections, and summarize progress toward clinical translation for lung‐derived exosome therapeutics.}, number={3}, journal={VIEW}, publisher={Wiley}, author={Popowski, Kristen D. and Dinh, Phuong-Uyen C. and George, Arianna and Lutz, Halle and Cheng, Ke}, year={2021}, month={Jun} }
 @article{hu_li_lutz_huang_su_cores_dinh_cheng_2020, title={Dermal exosomes containing miR-218-5p promote hair regeneration by regulating beta-catenin signaling}, volume={6}, ISSN={["2375-2548"]}, url={https://doi.org/10.1126/sciadv.aba1685}, DOI={10.1126/sciadv.aba1685}, abstractNote={Exosomes derived from dermal papilla spheroids express a high level of miR-218-5p, which directly regulates hair regeneration. The progression in the hair follicle cycle from the telogen to the anagen phase is the key to regulating hair regrowth. Dermal papilla (DP) cells support hair growth and regulate the hair cycle. However, they gradually lose key inductive properties upon culture. DP cells can partially restore their capacity to promote hair regrowth after being subjected to spheroid culture. In this study, results revealed that DP spheroids are effective at inducing the progression of the hair follicle cycle from telogen to anagen compared with just DP cell or minoxidil treatment. Because of the importance of paracrine signaling in this process, secretome and exosomes were isolated from DP cell culture, and their therapeutic efficacies were investigated. We demonstrated that miR-218-5p was notably up-regulated in DP spheroid–derived exosomes. Western blot and immunofluorescence imaging were used to demonstrate that DP spheroid–derived exosomes up-regulated β-catenin, promoting the development of hair follicles.}, number={30}, journal={SCIENCE ADVANCES}, publisher={American Association for the Advancement of Science (AAAS)}, author={Hu, Shiqi and Li, Zhenhua and Lutz, Halle and Huang, Ke and Su, Teng and Cores, Jhon and Dinh, Phuong-Uyen Cao and Cheng, Ke}, year={2020}, month={Jul} }
 @misc{popowski_lutz_hu_george_dinh_cheng_2020, title={Exosome therapeutics for lung regenerative medicine}, volume={9}, ISSN={["2001-3078"]}, url={https://doi.org/10.1080/20013078.2020.1785161}, DOI={10.1080/20013078.2020.1785161}, abstractNote={ABSTRACT Exosomes are 30 to 100 nm extracellular vesicles that are secreted by many cell types. Initially viewed as cellular garbage with no biological functions, exosomes are now recognized for their therapeutic potential and used in regenerative medicine. Cell-derived exosomes are released into almost all biological fluids, making them abundant and accessible vesicles for a variety of diseases. These naturally occurring nanoparticles have a wide range of applications including drug delivery and regenerative medicine. Exosomes sourced from a specific tissue have been proven to provide greater therapeutic effects to their native tissue, expanding exosome sources beyond traditional cell lines such as mesenchymal stem cells. However, standardizing production and passing regulations remain obstacles, due to variations in methods and quantification techniques across studies. Additionally, obtaining pure exosomes at sufficient quantities remains difficult due to the heterogeneity of exosomes. In this review, we will underline the uses of exosomes as a therapy and their roles in lung regenerative medicine, as well as current challenges in exosome therapies.}, number={1}, journal={JOURNAL OF EXTRACELLULAR VESICLES}, publisher={Wiley}, author={Popowski, Kristen and Lutz, Halle and Hu, Shiqi and George, Arianna and Dinh, Phuong-Uyen and Cheng, Ke}, year={2020}, month={Jan} }