Browsing by Author "Su, Teng"

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Open Access
An off-the-shelf artificial cardiac patch improves cardiac repair after myocardial infarction in rats and pigs.
(Science translational medicine, 2020-04) Huang, Ke; Ozpinar, Emily W; Su, Teng; Tang, Junnan; Shen, Deliang; Qiao, Li; Hu, Shiqi; Li, Zhenhua; Liang, Hongxia; Mathews, Kyle; Scharf, Valery; Freytes, Donald O; Cheng, Ke
Cell therapy has been a promising strategy for cardiac repair after injury or infarction; however, low retention and engraftment of transplanted cells limit potential therapeutic efficacy. Seeding scaffold material with cells to create cardiac patches that are transplanted onto the surface of the heart can overcome these limitations. However, because patches need to be freshly prepared to maintain cell viability, long-term storage is not feasible and limits clinical applicability. Here, we developed an off-the-shelf therapeutic cardiac patch composed of a decellularized porcine myocardial extracellular matrix scaffold and synthetic cardiac stromal cells (synCSCs) generated by encapsulating secreted factors from isolated human cardiac stromal cells. This fully acellular artificial cardiac patch (artCP) maintained its potency after long-term cryopreservation. In a rat model of acute myocardial infarction, transplantation of the artCP supported cardiac recovery by reducing scarring, promoting angiomyogenesis, and boosting cardiac function. The safety and efficacy of the artCP were further confirmed in a porcine model of myocardial infarction. The artCP is a clinically feasible, easy-to-store, and cell-free alternative to myocardial repair using cell-based cardiac patches.
Open Access
Antibody-Armed Platelets for the Regenerative Targeting of Endogenous Stem Cells.
(Nano letters, 2019-03) Shen, Deliang; Li, Zhenhua; Hu, Shiqi; Huang, Ke; Su, Teng; Liang, Hongxia; Liu, Feiran; Cheng, Ke
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.
Open Access
Biomimetics: Platelet-Inspired Nanocells for Targeted Heart Repair After Ischemia/Reperfusion Injury (Adv. Funct. Mater. 4/2019)
(Advanced Functional Materials, 2019-01) Su, Teng; Huang, Ke; Ma, Hong; Liang, Hongxia; Dinh, Phuong‐Uyen; Chen, Justin; Shen, Deliang; Allen, Tyler A; Qiao, Li; Li, Zhenhua; Hu, Shiqi; Cores, Jhon; Frame, Brianna N; Young, Ashlyn T; Yin, Qi; Liu, Jiandong; Qian, Li; Caranasos, Thomas G; Brudno, Yevgeny; Ligler, Frances S; Cheng, Ke
Open Access
BSA-rGO nanocomposite hydrogel formed by UV polymerization and in situ reduction applied as biosensor electrode.
(Journal of materials chemistry. B, 2013-10) Tang, Zhou; Gao, Lu; Wu, Yihua; Su, Teng; Wu, Qing; Liu, Xinhua; Li, Wenjun; Wang, Qigang
This communication demonstrates a convenient strategy to prepare a tough BSA-rGO hydrogel electrode via photopolymerization, which is demonstrated to be a highly effective H2O2 biosensor electrode with low detection concentration and high sensing sensitivity after combining with hemin chloride.
Open Access
Cardiac cell-integrated microneedle patch for treating myocardial infarction.
(Science advances, 2018-11) Tang, Junnan; Wang, Jinqiang; Huang, Ke; Ye, Yanqi; Su, Teng; Qiao, Li; Hensley, Michael Taylor; Caranasos, Thomas George; Zhang, Jinying; Gu, Zhen; Cheng, Ke
We engineered a microneedle patch integrated with cardiac stromal cells (MN-CSCs) for therapeutic heart regeneration after acute myocardial infarction (MI). To perform cell-based heart regeneration, cells are currently delivered to the heart via direct muscle injection, intravascular infusion, or transplantation of epicardial patches. The first two approaches suffer from poor cell retention, while epicardial patches integrate slowly with host myocardium. Here, we used polymeric MNs to create "channels" between host myocardium and therapeutic CSCs. These channels allow regenerative factors secreted by CSCs to be released into the injured myocardium to promote heart repair. In the rat MI model study, the application of the MN-CSC patch effectively augmented cardiac functions and enhanced angiomyogenesis. In the porcine MI model study, MN-CSC patch application was nontoxic and resulted in cardiac function protection. The MN system represents an innovative approach delivering therapeutic cells for heart regeneration.
Open Access
Cardiac Stem Cell Patch Integrated with Microengineered Blood Vessels Promotes Cardiomyocyte Proliferation and Neovascularization after Acute Myocardial Infarction.
(ACS applied materials & interfaces, 2018-10) Su, Teng; Huang, Ke; Daniele, Michael A; Hensley, Michael Taylor; Young, Ashlyn T; Tang, Junnan; Allen, Tyler A; Vandergriff, Adam C; Erb, Patrick D; Ligler, Frances S; Cheng, Ke
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.
Open Access
Cardiac Stromal Cell Patch Integrated with Engineered Microvessels Improves Recovery from Myocardial Infarction in Rats and Pigs.
(ACS biomaterials science & engineering, 2020-11) Su, Teng; Huang, Ke; Mathews, Kyle G; Scharf, Valery F; Hu, Shiqi; Li, Zhenhua; Frame, Brianna N; Cores, Jhon; Dinh, Phuong-Uyen; Daniele, Michael A; Ligler, Frances S; Cheng, Ke
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.
Open Access
Circulating tumor cells exit circulation while maintaining multicellularity, augmenting metastatic potential.
(Journal of cell science, 2019-09) Allen, Tyler A; Asad, Dana; Amu, Emmanuel; Hensley, M Taylor; Cores, Jhon; Vandergriff, Adam; Tang, Junnan; Dinh, Phuong-Uyen; Shen, Deliang; Qiao, Li; Su, Teng; Hu, Shiqi; Liang, Hongxia; Shive, Heather; Harrell, Erin; Campbell, Connor; Peng, Xinxia; Yoder, Jeffrey A; Cheng, Ke
Metastasis accounts for the majority of all cancer deaths, yet the process remains poorly understood. A pivotal step in the metastasis process is the exiting of tumor cells from the circulation, a process known as extravasation. However, it is unclear how tumor cells extravasate and whether multicellular clusters of tumor cells possess the ability to exit as a whole or must first disassociate. In this study, we use in vivo zebrafish and mouse models to elucidate the mechanism tumor cells use to extravasate. We found that circulating tumor cells exit the circulation using the recently identified extravasation mechanism, angiopellosis, and do so as both clusters and individual cells. We further show that when melanoma and cervical cancer cells utilize this extravasation method to exit as clusters, they exhibit an increased ability to form tumors at distant sites through the expression of unique genetic profiles. Collectively, we present a new model for tumor cell extravasation of both individual and multicellular circulating tumor cells.This article has an associated First Person interview with the first author of the paper.
Open Access
Dermal exosomes containing miR-218-5p promote hair regeneration by regulating β-catenin signaling.
(Science advances, 2020-07) Hu, Shiqi; Li, Zhenhua; Lutz, Halle; Huang, Ke; Su, Teng; Cores, Jhon; Dinh, Phuong-Uyen Cao; Cheng, Ke
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.
Open Access
Dual enzymatic formation of hybrid hydrogels with supramolecular-polymeric networks.
(Chemical communications (Cambridge, England), 2014-11) Mao, Yanjie; Su, Teng; Wu, Qing; Liao, Chuanan; Wang, Qigang
This communication describes a mild construction of hybrid hydrogels with supramolecular-polymeric networks via a dual enzymatic reaction.
Open Access
Dual-Enzyme-Loaded Multifunctional Hybrid Nanogel System for Pathological Responsive Ultrasound Imaging and T2-Weighted Magnetic Resonance Imaging.
(ACS nano, 2015-06) Wang, Xia; Niu, Dechao; Li, Pei; Wu, Qing; Bo, Xiaowan; Liu, Boji; Bao, Song; Su, Teng; Xu, Huixiong; Wang, Qigang
A dual-enzyme-loaded multifunctional hybrid nanogel probe (SPIO@GCS/acryl/biotin-CAT/SOD-gel, or SGC) has been developed for dual-modality pathological responsive ultrasound (US) imaging and enhanced T2-weighted magnetic resonance (MR) imaging. This probe is composed of functionalized superparamagnetic iron oxide particles, a dual enzyme species (catalase and superoxide dismutase), and a polysaccharide cationic polymer glycol chitosan gel. The dual-modality US/MR imaging capabilities of the hybrid nanogel for responsive US imaging and enhanced T2-weighted MR imaging have been evaluated both in vitro and in vivo. These results show that the hybrid nanogel SGC can exhibit efficient dual-enzyme biocatalysis with pathological species for responsive US imaging. SGC also demonstrates increased accumulation in acidic environments for enhanced T2-weighted MR imaging. Further research on these nanogel systems may lead to the development of more efficient US/MR contrast agents.
Open Access
Exosome and Biomimetic Nanoparticle Therapies for Cardiac Regenerative Medicine.
(Current stem cell research & therapy, 2020-01) Stine, Sydney J; Popowski, Kristen D; Su, Teng; Cheng, Ke
Exosomes and biomimetic nanoparticles have great potential to develop into a wide-scale therapeutic platform within the regenerative medicine industry. Exosomes, a subgroup of EVs with diameter ranging from 30-100 nm, have recently gained attention as an innovative approach for the treatment of various diseases, including heart disease. Their beneficial factors and regenerative properties can be contrasted with various cell types. Various biomimetic nanoparticles have also emerged as a unique platform in regenerative medicine. Biomimetic nanoparticles are a drug delivery platform, which have the ability to contain both biological and fabricated components to improve therapeutic efficiency and targeting. The novelty of these platforms holds promise for future clinical translation upon further investigation. In order for both exosome therapeutics and biomimetic nanoparticles to translate into large-scale clinical treatment, numerous factors must first be considered and improved. Standardization of different protocols, from exosome isolation to storage conditions, must be optimized to ensure batches are pure. Standardization is also important to ensure no variability in this process across studies, thus making it easier to interpret data across different disease models and treatments. Expansion of clinical trials incorporating both biomimetic nanoparticles and exosomes will require a standardization of fabrication and isolation techniques, as well as stricter regulations to ensure reproducibility across various studies and disease models. This review will summarize current research on exosome therapeutics and the application of biomimetic nanoparticles in cardiac regenerative medicine, as well as applications for exosome expansion and delivery on a large clinical scale.
Open Access
Exosome-eluting stents for vascular healing after ischaemic injury.
(Nature biomedical engineering, 2021-10) Hu, Shiqi; Li, Zhenhua; Shen, Deliang; Zhu, Dashuai; Huang, Ke; Su, Teng; Dinh, Phuong-Uyen; Cores, Jhon; Cheng, Ke
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.
Open Access
Functional elastic hydrogel as recyclable membrane for the adsorption and degradation of methylene blue.
(PloS one, 2014-01) Bao, Song; Wu, Dongbei; Wang, Qigang; Su, Teng
Developing the application of high-strength hydrogels has gained much attention in the fields of medical, pharmacy, and pollutant removal due to their versatility and stimulus-responsive properties. In this presentation, a high-strength freestanding elastic hydrogel membrane was constructed by clay nanosheets, N, N-dimethylacrylamide and 2-acrylamide-2-methylpropanesulfonic acid for adsorption of methylene blue and heavy metal ions. The maximum values of elongation and Young's modulus for 0.5% AMPSNa hydrogel were 1901% and 949.4 kPa, respectively, much higher than those of traditional hydrogels. The adsorptions were confirmed to follow pseudo-second kinetic equation and Langmuir isotherm model fits the data well. The maximum adsorption capacity of hydrogel towards methylene blue was 434.8 mg g(-1). The hydrogel also exhibited higher separation selectivity to Pb(2+) than Cu(2+). The methylene blue adsorbed onto the hydrogel membrane can be photocatalytically degraded by Fenton agent and the hydrogel membrane could be recycled at least five times without obvious loss in mechanical properties. In conclusion, this presentation demonstrates a convenient strategy to prepare tough and elastic clay nanocomposite hydrogel, which can not only be applied as recyclable membrane for the photocatalytic degradation of organic dye, but also for the recovery of valuables.
Open Access
HRP-mediated polymerization forms tough nanocomposite hydrogels with high biocatalytic performance.
(Chemical communications (Cambridge, England), 2013-09) Su, Teng; Zhang, Da; Tang, Zhou; Wu, Qing; Wang, Qigang
This communication describes the mild and quick construction of tough nanocomposite hydrogels via a horseradish peroxidase-mediated radical polymerization for effectively immobilizing enzymes to attain high catalytic performance in various solvents.
Open Access
Hyaluronic Acid Hydrogel Integrated with Mesenchymal Stem Cell-Secretome to Treat Endometrial Injury in a Rat Model of Asherman's Syndrome.
(Advanced healthcare materials, 2019-07) Liu, Feiran; Hu, Shiqi; Yang, Hua; Li, Zhenhua; Huang, Ke; Su, Teng; Wang, Shaowei; Cheng, Ke
Stem cell therapies have made strides toward the efficacious treatment of injured endometrium and the prevention of intrauterine adhesions, or Asherman's syndrome (AS). Despite this progress, they are limited by their risk of tumor formation, low engraftment rates, as well as storage and transportation logistics. While attempts have been made to curb these issues, there remains a need for simple and effective solutions. A growing body of evidence supports the theory that delivering media, conditioned with mesenchymal stem cells, might be a promising alternative to live cell therapy. Mesenchymal stem cell-secretome (MSC-Sec) has a superior safety profile and can be stored without losing its regenerative properties. It is versatile enough to be added to a number of delivery vehicles that improve engraftment and control the release of the therapeutic. Thus, it holds great potential for the treatment of AS. Here, a new strategy for loading crosslinked hyaluronic acid gel (HA gel) with MSC-Sec is reported. The HA gel/MSC-Sec treatment paradigm creates a sustained release system that repairs endometrial injury in rats and promotes viable pregnancy.
Open Access
Iron oxide/manganese oxide co-loaded hybrid nanogels as pH-responsive magnetic resonance contrast agents.
(Biomaterials, 2015-01) Wang, Xia; Niu, Dechao; Wu, Qing; Bao, Song; Su, Teng; Liu, Xiaohang; Zhang, Shengjian; Wang, Qigang
This work described a proof of concept study of hybrid nanogel-based magnetic resonance contrast agents, SPIO@GCS/acryl/biotin@Mn-gel, abb. as SGM, for highly efficient, pH-responsive T1 and T2 dual-mode magnetic resonance imaging (MRI). SGM have been synthesized by assembling superparamagnetic iron oxide particles into polysaccharide nanoclusters, followed by in-situ reduction of the manganese species on the clusters and a final mild polymerization. The dual-mode SGM showed an interesting pH-responsiveness in in vitro MRI, with both T1 and T2 relaxivities turned "ON" in the acidic environment, along with an increase in the r1 and r2 relaxivity values by 1.7-fold (from 8.9 to 15.3 mM(-1) S(-1)) and 4.9-fold (from 45.7 to 226 mM(-1) S(-1)), due to desirable silencing and de-silencing effects. This interesting acidic-responsiveness was further verified in vivo with both significantly brightened signal of tumor tissue in T1-weighted MR images and a darkened signal in T2-weighted MR images 50 min post-injection of SGM. This smart hybrid nanogel may serve as a promising candidate for further studies of dual-mode (T1 and T2) contrast agents in MRI, due to its high stability, interesting pH-response mechanism and indicative imaging of tumors.
Open Access
Magnetic nanocomposite hydrogel prepared by ZnO-initiated photopolymerization for La (III) adsorption.
(ACS applied materials & interfaces, 2014-11) Zheng, Xiangning; Wu, Dongbei; Su, Teng; Bao, Song; Liao, Chuanan; Wang, Qigang
Here, we provide an effective method to fabricate magnetic ZnO clay nanocomposite hydrogel via the photopolymerization. The inorganic components endow the hydrogel with high mechanical strength, while the organic copolymers exhibit good adsorption capacity and separation selectivity to La (III) ions. An optimized hydrogel has the maximum compressive stress of 316.60±15.83 kPa, which still exhibits 138.98±7.32 kPa compressive strength after swelling. The maximum adsorption capacity of La ion is 58.8 mg/g. The adsorption matches the pseudo-second-order kinetics model. La (III) ions can be effectively separated from the mixtures of La/Ni, La/Co, La/Cu, and La/Nd in a broad pH range (2.0 to 8.0). After six adsorption-desorption cycles, the hydrogel can maintain its adsorption capacity. This work not only provides a new approach to the synthesis of tough hydrogels under irradiation, but also opens up enormous opportunities to make full use of magnetic nanocomposite hydrogels in environmental fields.
Open Access
Mesenchymal Stem Cell/Red Blood Cell-Inspired Nanoparticle Therapy in Mice with Carbon Tetrachloride-Induced Acute Liver Failure.
(ACS nano, 2018-07) Liang, Hongxia; Huang, Ke; Su, Teng; Li, Zhenhua; Hu, Shiqi; Dinh, Phuong-Uyen; Wrona, Emily A; Shao, Chen; Qiao, Li; Vandergriff, Adam C; Hensley, M Taylor; Cores, Jhon; Allen, Tyler; Zhang, Hongyu; Zeng, Qinglei; Xing, Jiyuan; Freytes, Donald O; Shen, Deliang; Yu, Zujiang; Cheng, Ke
Acute liver failure is a critical condition characterized by global hepatocyte death and often time needs a liver transplantation. Such treatment is largely limited by donor organ shortage. Stem cell therapy offers a promising option to patients with acute liver failure. Yet, therapeutic efficacy and feasibility are hindered by delivery route and storage instability of live cell products. We fabricated a nanoparticle that carries the beneficial regenerative factors from mesenchymal stem cells and further coated it with the membranes of red blood cells to increase blood stability. Unlike uncoated nanoparticles, these particles promote liver cell proliferation in vitro and have lower internalization by macrophage cells. After intravenous delivery, these artificial stem cell analogs are able to remain in the liver and mitigate carbon tetrachloride-induced liver failure in a mouse model, as gauged by histology and liver function test. Our technology provides an innovative and off-the-shelf strategy to treat liver failure.
Open Access
microRNA-21-5p dysregulation in exosomes derived from heart failure patients impairs regenerative potential.
(The Journal of clinical investigation, 2019-04) Qiao, Li; Hu, Shiqi; Liu, Suyun; Zhang, Hui; Ma, Hong; Huang, Ke; Li, Zhenhua; Su, Teng; Vandergriff, Adam; Tang, Junnan; Allen, Tyler; Dinh, Phuong-Uyen; Cores, Jhon; Yin, Qi; Li, Yongjun; Cheng, Ke
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.