@article{hu_li_shen_zhu_huang_su_dinh_cores_cheng_2021, title={Exosome-eluting stents for vascular healing after ischaemic injury}, volume={5}, ISSN={["2157-846X"]}, url={https://doi.org/10.1038/s41551-021-00705-0}, DOI={10.1038/s41551-021-00705-0}, abstractNote={Drug-eluting stents implanted after ischaemic injury reduce the proliferation of endothelial cells and vascular smooth muscle cells and thus neointimal hyperplasia. However, the eluted drug also slows down the re-endothelialization process, delays arterial healing and can increase the risk of late restenosis. Here we show that stents releasing exosomes derived from mesenchymal stem cells in the presence of reactive oxygen species enhance vascular healing in rats with renal ischaemia-reperfusion injury, promoting endothelial cell tube formation and proliferation, and impairing the migration of smooth muscle cells. Compared with drug-eluting stents and bare-metal stents, the exosome-coated stents accelerated re-endothelialization and decreased in-stent restenosis 28 days after implantation. We also show that exosome-eluting stents implanted in the abdominal aorta of rats with unilateral hindlimb ischaemia regulated macrophage polarization, reduced local vascular and systemic inflammation, and promoted muscle tissue repair. Exosome-eluting stents implanted in rats after ischaemic injury accelerate vascular healing and promote tissue regeneration.}, number={10}, journal={NATURE BIOMEDICAL ENGINEERING}, publisher={Springer Science and Business Media LLC}, author={Hu, Shiqi and Li, Zhenhua and Shen, Deliang and Zhu, Dashuai and Huang, Ke and Su, Teng and Dinh, Phuong-Uyen and Cores, Jhon and Cheng, Ke}, year={2021}, month={Oct}, pages={1174–1188} }
 @article{hu_wang_li_zhu_cores_wang_li_mei_cheng_su_et al._2021, title={Platelet membrane and stem cell exosome hybrids enhance cellular uptake and targeting to heart injury}, volume={39}, ISSN={["1878-044X"]}, url={http://www.scopus.com/inward/record.url?eid=2-s2.0-85107566346&partnerID=MN8TOARS}, DOI={10.1016/j.nantod.2021.101210}, abstractNote={Exosomes from mesenchymal stem cells have been largely studied as therapeutics to treat myocardial infarctions. However, exosomes injected for therapeutic purposes face a number of challenges, including competition from exosomes already in circulation, and the internalization/clearance by the mononuclear phagocyte system. In this study, we hybrid exosomes with platelet membranes to enhance their ability to target the injured heart and avoid being captured by macrophages. Furthermore, we found that encapsulation by the platelet membranes induces macropinocytosis, enhancing the cellular uptake of exosomes by endothelial cells and cardiomyocytes strikingly. In vivo studies showed that the cardiac targeting ability of hybrid exosomes in a mice model with myocardial infarction injury. Last, we tested cardiac functions and performed immunohistochemistry to confirm a better therapeutic effect of platelet membrane modified exosomes compared to non-modified exosomes. Our studies provide proof-of-concept data and a universal approach to enhance the binding and accumulation of exosomes in injured tissues.}, journal={NANO TODAY}, author={Hu, Shiqi and Wang, Xianyun and Li, Zhenhua and Zhu, Dashuai and Cores, Jhon and Wang, Zhenzhen and Li, Junlang and Mei, Xuan and Cheng, Xiao and Su, Teng and et al.}, year={2021}, month={Aug} }
 @article{su_huang_mathews_scharf_hu_li_frame_cores_dinh_daniele_et al._2020, title={Cardiac Stromal Cell Patch Integrated with Engineered Microvessels Improves Recovery from Myocardial Infarction in Rats and Pigs}, volume={6}, ISSN={["2373-9878"]}, DOI={10.1021/acsbiomaterials.0c00942}, abstractNote={The vascularized cardiac patch strategy is promising for ischemic heart repair after myocardial infarction (MI), but current fabrication processes are quite complicated. Vascularized cardiac patches that can promote concurrent restoration of both the myocardium and vasculature at the injured site in a large animal model remain elusive. The safety and therapeutic benefits of a cardiac stromal cell patch integrated with engineered biomimetic microvessels (BMVs) were determined for treating MI. By leveraging a microfluidic method employing hydrodynamic focusing, we constructed the endothelialized microvessels and then encapsulated them together with therapeutic cardiosphere-derived stromal cells (CSCs) in a fibrin gel to generate a prevascularized cardiac stromal cell patch (BMV-CSC patch). We showed that BMV-CSC patch transplantation significantly promoted cardiac function, reduced scar size, increased viable myocardial tissue, promoted neovascularization, and suppressed inflammation in rat and porcine MI models, demonstrating enhanced therapeutic efficacy compared to conventional cardiac stromal cell patches. BMV-CSC patches did not increase renal and hepatic toxicity or exhibit immunogenicity. We noted a significant increase in endogenous progenitor cell recruitment to the peri-infarct region of the porcine hearts treated with BMV-CSC patch as compared to those that received control treatments. These findings establish the BMV-CSC patch as a novel engineered-tissue therapeutic for ischemic tissue repair.}, number={11}, journal={ACS BIOMATERIALS SCIENCE & ENGINEERING}, author={Su, Teng and Huang, Ke and Mathews, Kyle G. and Scharf, Valery F. and Hu, Shiqi and Li, Zhenhua and Frame, Brianna N. and Cores, Jhon and Dinh, Phuong-Uyen and Daniele, Michael A. and et al.}, year={2020}, month={Nov}, pages={6309–6320} }
 @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.}, 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} }
 @article{li_hu_huang_su_cores_cheng_2020, title={Targeted anti-IL-1 beta platelet microparticles for cardiac detoxing and repair}, volume={6}, ISSN={["2375-2548"]}, url={https://doi.org/10.1126/sciadv.aay0589}, DOI={10.1126/sciadv.aay0589}, abstractNote={Platelet microparticles are used to deliver IL-1β antibodies to myocardial infarction for cardiac detoxing and repair.}, number={6}, journal={SCIENCE ADVANCES}, publisher={American Association for the Advancement of Science (AAAS)}, author={Li, Zhenhua and Hu, Shiqi and Huang, Ke and Su, Teng and Cores, Jhon and Cheng, Ke}, year={2020}, month={Feb} }
 @article{qiao_hu_huang_su_li_vandergriff_cores_dinh_allen_shen_et al._2020, title={Tumor cell-derived exosomes home to their cells of origin and can be used as Trojan horses to deliver cancer drugs}, volume={10}, ISSN={["1838-7640"]}, DOI={10.7150/thno.39434}, abstractNote={Cancer is the second leading cause of death worldwide and patients are in urgent need of therapies that can effectively target cancer with minimal off-target side effects. Exosomes are extracellular nano-shuttles that facilitate intercellular communication between cells and organs. It has been established that tumor-derived exosomes contain a similar protein and lipid composition to that of the cells that secrete them, indicating that exosomes might be uniquely employed as carriers for anti-cancer therapeutics. Methods: We isolated exosomes from two cancer cell lines, then co-cultured each type of cancer cells with these two kinds of exosomes and quantified exosome. HT1080 or Hela exosomes were systemically injected to Nude mice bearing a subcutaneous HT1080 tumor to investigate their cancer-homing behavior. Moreover, cancer cell-derived exosomes were engineered to carry Doxil (a common chemotherapy drug), known as D-exo, were used to detect their target and therapeutic efficacy as anti-cancer drugs. Exosome proteome array analysis were used to reveal the mechanism underly this phenomenon. Results: Exosomes derived from cancer cells fuse preferentially with their parent cancer cells, in vitro. Systemically injected tumor-derived exosomes home to their original tumor tissues. Moreover, compared to Doxil alone, the drug-loaded exosomes showed enhanced therapeutic retention in tumor tissues and eradicated them more effectively in nude mice. Exosome proteome array analysis revealed distinct integrin expression patterns, which might shed light on the underlying mechanisms that explain the exosomal cancer-homing behavior. Conclusion: Here we demonstrate that the exosomes' ability to target the parent cancer is a phenomenon that opens up new ways to devise targeted therapies to deliver anti-tumor drugs.}, number={8}, journal={THERANOSTICS}, author={Qiao, Li and Hu, Shiqi and Huang, Ke and Su, Teng and Li, Zhenhua and Vandergriff, Adam and Cores, Jhon and Dinh, Phuong-Uyen and Allen, Tyler and Shen, Deliang and et al.}, year={2020}, pages={3474–3487} }
 @article{shen_li_hu_huang_su_liang_liu_cheng_2019, title={Antibody-Armed Platelets for the Regenerative Targeting of Endogenous Stem Cells}, volume={19}, ISSN={["1530-6992"]}, DOI={10.1021/acs.nanolett.8b04970}, abstractNote={Stem cell therapies have shown promise in treating acute and chronic ischemic heart disease. However, current therapies are limited by the low retention and poor integration of injected cells in the injured tissue. Taking advantage of the natural infarct-homing ability of platelets, we engineered CD34 antibody-linked platelets (P-CD34) to capture circulating CD34-positive endogenous stem cells and direct them to the injured heart. In vitro, P-CD34 could bind to damaged aortas and capture endogenous stem cells in whole blood. In a mouse model of acute myocardial infarction, P-CD34 accumulated in the injured heart after intravenous administration, leading to a concentration of endogenous CD34 stem cells in the injured heart for effective heart repair. This represents a new technology for endogenous stem cell therapy.}, number={3}, journal={NANO LETTERS}, author={Shen, Deliang and Li, Zhenhua and Hu, Shiqi and Huang, Ke and Su, Teng and Liang, Hongxia and Liu, Feiran and Cheng, Ke}, year={2019}, month={Mar}, pages={1883–1891} }
 @article{huang_li_su_shen_hu_cheng_2019, title={Bispecific Antibody Therapy for Effective Cardiac Repair through Redirection of Endogenous Stem Cells}, volume={2}, ISSN={["2366-3987"]}, DOI={10.1002/adtp.201900009}, abstractNote={Abstract}, number={10}, journal={ADVANCED THERAPEUTICS}, author={Huang, Ke and Li, Zhenhua and Su, Teng and Shen, Deliang and Hu, Shiqi and Cheng, Ke}, year={2019}, month={Oct} }
 @article{liu_hu_yang_li_huang_su_wang_cheng_2019, title={Hyaluronic Acid Hydrogel Integrated with Mesenchymal Stem Cell-Secretome to Treat Endometrial Injury in a Rat Model of Asherman's Syndrome}, volume={8}, ISSN={["2192-2659"]}, DOI={10.1002/adhm.201900411}, abstractNote={Abstract}, number={14}, journal={ADVANCED HEALTHCARE MATERIALS}, author={Liu, Feiran and Hu, Shiqi and Yang, Hua and Li, Zhenhua and Huang, Ke and Su, Teng and Wang, Shaowei and Cheng, Ke}, year={2019}, month={Jul} }
 @article{hu_li_cores_huang_su_dinh_cheng_2019, title={Needle-Free Injection of Exosomes Derived from Human Dermal Fibroblast Spheroids Ameliorates Skin Photoaging}, volume={13}, ISSN={["1936-086X"]}, DOI={10.1021/acsnano.9b04384}, abstractNote={Human dermal fibroblasts (HDFs), the main cell population of the dermis, gradually lose their ability to produce collagen and renew intercellular matrix with aging. One clinical application for the autologous trans-dermis injection of HDFs that has been approved by the Food and Drug Administration aims to refine facial contours and slow down skin aging. However, the autologous HDFs used vary in quality according to the state of patients and due to many passages they undergo during expansion. In this study, factors and exosomes derived from three-dimensional spheroids (3D HDF-XOs) and the monolayer culture of HDFs (2D HDF-XOs) were collected and compared. 3D HDF-XOs expressed a significantly higher level of tissue inhibitor of metalloproteinases-1 (TIMP-1) and differentially expressed miRNA cargos compared with 2D HDF-XOs. Next, the efficacy of 3D HDF-XOs in inducing collagen synthesis and antiaging was demonstrated in vitro and in a nude mouse photoaging model. A needle-free injector was used to administer exosome treatments. 3D HDF-XOs caused increased procollagen type I expression and a significant decrease in MMP-1 expression, mainly through the downregulation of tumor necrosis factor-alpha (TNF-α) and the upregulation of transforming growth factor beta (TGF-β). In addition, the 3D-HDF-XOs group showed a higher level of dermal collagen deposition than bone marrow mesenchymal stem cell-derived exosomes. These results indicate that exosomes from 3D cultured HDF spheroids have anti-skin-aging properties and the potential to prevent and treat cutaneous aging.}, number={10}, journal={ACS NANO}, author={Hu, Shiqi and Li, Zhenhua and Cores, Jhon and Huang, Ke and Su, Teng and Dinh, Phuong-Uyen and Cheng, Ke}, year={2019}, month={Oct}, pages={11273–11282} }
 @article{su_huang_ma_liang_dinh_chen_shen_allen_qiao_li_et al._2019, title={Platelet-Inspired Nanocells for Targeted Heart Repair After Ischemia/Reperfusion Injury}, volume={29}, ISSN={["1616-3028"]}, DOI={10.1002/adfm.201803567}, abstractNote={Abstract}, number={4}, journal={ADVANCED FUNCTIONAL MATERIALS}, author={Su, Teng and Huang, Ke and Ma, Hong and Liang, Hongxia and Dinh, Phuong-Uyen and Chen, Justin and Shen, Deliang and Allen, Tyler A. and Qiao, Li and Li, Zhenhua and et al.}, year={2019}, month={Jan} }
 @article{qiao_hu_liu_zhang_ma_huang_li_su_vandergrif_tang_et al._2019, title={microRNA-21-5p dysregulation in exosomes derived from heart failure patients impairs regenerative potential}, volume={129}, ISSN={["1558-8238"]}, url={https://doi.org/10.1172/JCI123135}, DOI={10.1172/JCI123135}, abstractNote={Exosomes, as functional paracrine units of therapeutic cells, can partially reproduce the reparative properties of their parental cells. The constitution of exosomes, as well as their biological activity, largely depends on the cells that secrete them. We isolated exosomes from explant-derived cardiac stromal cells from patients with heart failure (FEXO) or from normal donor hearts (NEXO) and compared their regenerative activities in vitro and in vivo. Patients in the FEXO group exhibited an impaired ability to promote endothelial tube formation and cardiomyocyte proliferation in vitro. Intramyocardial injection of NEXO resulted in structural and functional improvements in a murine model of acute myocardial infarction. In contrast, FEXO therapy exacerbated cardiac function and left ventricular remodeling. microRNA array and PCR analysis revealed dysregulation of miR-21-5p in FEXO. Restoring miR-21-5p expression rescued FEXO's reparative function, whereas blunting miR-21-5p expression in NEXO diminished its therapeutic benefits. Further mechanistic studies revealed that miR-21-5p augmented Akt kinase activity through the inhibition of phosphatase and tensin homolog. Taken together, the heart failure pathological condition altered the miR cargos of cardiac-derived exosomes and impaired their regenerative activities. miR-21-5p contributes to exosome-mediated heart repair by enhancing angiogenesis and cardiomyocyte survival through the phosphatase and tensin homolog/Akt pathway.}, number={6}, journal={JOURNAL OF CLINICAL INVESTIGATION}, publisher={American Society for Clinical Investigation}, author={Qiao, Li and Hu, Shiqi and Liu, Suyun and Zhang, Hui and Ma, Hong and Huang, Ke and Li, Zhenhua and Su, Teng and Vandergrif, Adam and Tang, Junnan and et al.}, year={2019}, month={Jun}, pages={2237–2250} }
 @article{su_huang_daniele_hensley_young_tang_allen_vandergriff_erb_ligler_et al._2018, title={Cardiac Stem Cell Patch Integrated with Microengineered Blood Vessels Promotes Cardiomyocyte Proliferation and Neovascularization after Acute Myocardial Infarction}, volume={10}, ISSN={["1944-8252"]}, DOI={10.1021/acsami.8b13571}, abstractNote={Cardiac stem cell (CSC) therapy has shown preclinical and clinical evidence for ischemic heart repair but is limited by low cellular engraftment and survival after transplantation. Previous versions of the cardiac patch strategy improve stem cell engraftment and encourage repair of cardiac tissue. However, cardiac patches that can enhance cardiomyogenesis and angiogenesis at the injured site remain elusive. Therapies that target cardiomyocyte proliferation and new blood vessel formation hold great potential for the protection against acute myocardial infarction (MI). Here, we report a new strategy for creating a vascularized cardiac patch in a facile and modular fashion by leveraging microfluidic hydrodynamic focusing to construct the biomimetic microvessels (BMVs) that include human umbilical vein endothelial cells (HUVECs) lining the luminal surface and then encapsulating the BMVs in a fibrin gel spiked with human CSCs. We show that the endothelialized BMVs mimicked the natural architecture and function of capillaries and that the resultant vascularized cardiac patch (BMV-CSC patch) exhibited equivalent release of paracrine factors compared to those of coculture of genuine human CSCs and HUVECs after 7 days of in vitro culture. In a rat model of acute MI, the BMV-CSC patch therapy induced profound mitotic activities of cardiomyocytes in the peri-infarct region 4 weeks post-treatment. A significant increase in myocardial capillary density was noted in the infarcted hearts that received BMV-CSC patch treatment compared to the infarcted hearts treated with conventional CSC patches. The striking therapeutic benefits and the fast and facile fabrication of the BMV-CSC patch make it promising for practical applications. Our findings suggest that the BMV-CSC patch strategy may open up new possibilities for the treatment of ischemic heart injury.}, number={39}, journal={ACS APPLIED MATERIALS & INTERFACES}, author={Su, Teng and Huang, Ke and Daniele, Michael A. and Hensley, Michael Taylor and Young, Ashlyn T. and Tang, Junnan and Allen, Tyler A. and Vandergriff, Adam C. and Erb, Patrick D. and Ligler, Frances S. and et al.}, year={2018}, month={Oct}, pages={33088–33096} }
 @article{tang_wang_huang_ye_su_qiao_hensley_caranasos_zhang_gu_et al._2018, title={Cardiac cell-integrated microneedle patch for treating myocardial infarction}, volume={4}, ISSN={["2375-2548"]}, url={https://doi.org/10.1126/sciadv.aat9365}, DOI={10.1126/sciadv.aat9365}, abstractNote={A microneedle cardiac stromal cell patch has been developed for therapeutic heart regeneration after myocardial infarction.}, number={11}, journal={SCIENCE ADVANCES}, publisher={American Association for the Advancement of Science (AAAS)}, author={Tang, Junnan and Wang, Jinqiang and Huang, Ke and Ye, Yanqi and Su, Teng and Qiao, Li and Hensley, Michael Taylor and Caranasos, Thomas George and Zhang, Jinying and Gu, Zhen and et al.}, year={2018}, month={Nov} }
 @article{li_shen_hu_su_huang_liu_hou_cheng_2018, title={Pretargeting and Bioorthogonal Click Chemistry-Mediated Endogenous Stem Cell Homing for Heart Repair}, volume={12}, ISSN={["1936-086X"]}, DOI={10.1021/acsnano.8b05892}, abstractNote={Stem cell therapy is one of the promising strategies for the treatment of ischemic heart disease. However, the clinical application of stem cells transplantation is limited by low cell engraftment in the infarcted myocardium. Taking advantage of pretargeting and bioorthogonal chemistry, we engineered a pretargeting and bioorthogonal chemistry (PTBC) system to capture endogenous circulating stem cells and target them to the injured heart for effective repair. Two bioorthogonal antibodies were i.v. administrated with a pretargeting interval (48 h). Through bioorthogonal click reaction, the two antibodies are linked in vivo, engaging endogenous stem cells with circulating platelets. As a result, the platelets redirect the stem cells to the injured heart. In vitro and in vivo studies demonstrated that bioorthogonal click reaction was able to induce the conjugation of platelets and endothelial progenitor cells (EPCs) and enhance the binding of EPCs to collagen and injured blood vessels. More importantly, in a mouse model of acute myocardial infarction, the in vivo results of cardiac function, heart morphometry, and immunohistochemistry assessment all confirmed effective heart repair by the PTBC system.}, number={12}, journal={ACS NANO}, author={Li, Zhenhua and Shen, Deliang and Hu, Shiqi and Su, Teng and Huang, Ke and Liu, Feiran and Hou, Lei and Cheng, Ke}, year={2018}, month={Dec}, pages={12193–12200} }
 @article{tang_su_huang_dinh_wang_vandergriff_hensley_cores_allen_li_et al._2018, title={Targeted repair of heart injury by stem cells fused with platelet nanovesicles}, volume={2}, ISSN={["2157-846X"]}, url={https://europepmc.org/articles/PMC5976251}, DOI={10.1038/s41551-017-0182-x}, abstractNote={Stem cell transplantation, as used clinically, suffers from low retention and engraftment of the transplanted cells. Inspired by the ability of platelets to recruit stem cells to sites of injury on blood vessels, we hypothesized that platelets might enhance the vascular delivery of cardiac stem cells (CSCs) to sites of myocardial infarction injury. Here, we show that CSCs with platelet nanovesicles fused onto their surface membranes express platelet surface markers that are associated with platelet adhesion to injury sites. We also find that the modified CSCs selectively bind collagen-coated surfaces and endothelium-denuded rat aortas, and that in rat and porcine models of acute myocardial infarction the modified CSCs increase retention in the heart and reduce infarct size. Platelet-nanovesicle-fused CSCs thus possess the natural targeting and repairing ability of their parental cell types. This stem cell manipulation approach is fast, straightforward and safe, does not require genetic alteration of the cells, and should be generalizable to multiple cell types. The attachment of platelet nanovesicles to the surface of cardiac stem cells increases the retention of the cells delivered to the heart and reduces infarct size in rat and pig models of acute myocardial infarction.}, number={1}, journal={NATURE BIOMEDICAL ENGINEERING}, author={Tang, Junnan and Su, Teng and Huang, Ke and Dinh, Phuong-Uyen and Wang, Zegen and Vandergriff, Adam and Hensley, Michael T. and Cores, Jhon and Allen, Tyler and Li, Taosheng and et al.}, year={2018}, month={Jan}, pages={17–26} }
 @article{su_liu_he_li_lv_zhang_sun_hu_2016, title={Strong Bioinspired Polymer Hydrogel with Tunable Stiffness and Toughness for Mimicking the Extracellular Matrix}, volume={5}, ISSN={["2161-1653"]}, DOI={10.1021/acsmacrolett.6b00702}, abstractNote={Inspired by the delicate architecture of hyaline articular cartilage, we report on a biomimetic polymer hydrogel that incorporates strong intermolecular hydrogen bonding between urethane-urethane linkages as well as urethane-ester linkages. The resultant hydrogel, containing ≈75% water, can endure a compressive stress up to 56 MPa with a strain of 98%, and exhibit tunable compressive modulus (0.19-1.38 MPa), as well as toughness (3629-28290 J m-2) within a wide range. The tensile strength and elastic modulus reach as high as 0.56 and 5.5 MPa, respectively. The high stiffness and toughness enable the gel to withstand cyclic compressive loadings without fracturing. Moreover, our hydrogel mimics the extracellular matrices of cartilage and bone tissues and provides biochemical and physical cues that support the three-dimensional proliferation of chondrocytes and osteogenic differentiation of preosteoblasts.}, number={11}, journal={ACS MACRO LETTERS}, author={Su, Teng and Liu, Yi and He, Hongjian and Li, Jia and Lv, Yanan and Zhang, Lili and Sun, Yao and Hu, Chunpu}, year={2016}, month={Nov}, pages={1217–1221} }