Browsing by Author "Shen, Deliang"

Now showing 1 - 11 of 11

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
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
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
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
Platelet-Inspired Nanocells for Targeted Heart Repair After Ischemia/Reperfusion Injury.
(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
Cardiovascular disease is the leading cause of mortality worldwide. While reperfusion therapy is vital for patient survival post-heart attack, it also causes further tissue injury, known as myocardial ischemia/reperfusion (I/R) injury in clinical practice. Exploring ways to attenuate I/R injury is of clinical interest for improving post-ischemic recovery. A platelet-inspired nanocell (PINC) that incorporates both prostaglandin E2 (PGE2)-modified platelet membrane and cardiac stromal cell-secreted factors to target the heart after I/R injury is introduced. By taking advantage of the natural infarct-homing ability of platelet membrane and the overexpression of PGE2 receptors (EPs) in the pathological cardiac microenvironment after I/R injury, the PINCs can achieve targeted delivery of therapeutic payload to the injured heart. Furthermore, a synergistic treatment efficacy can be achieved by PINC, which combines the paracrine mechanism of cell therapy with the PGE2/EP receptor signaling that is involved in the repair and regeneration of multiple tissues. In a mouse model of myocardial I/R injury, intravenous injection of PINCs results in augmented cardiac function and mitigated heart remodeling, which is accompanied by the increase in cycling cardiomyocytes, activation of endogenous stem/progenitor cells, and promotion of angiogenesis. This approach represents a promising therapeutic delivery platform for treating I/R injury.
Open Access
Pretargeting and Bioorthogonal Click Chemistry-Mediated Endogenous Stem Cell Homing for Heart Repair.
(ACS nano, 2018-12) Li, Zhenhua; Shen, Deliang; Hu, Shiqi; Su, Teng; Huang, Ke; Liu, Feiran; Hou, Lei; Cheng, Ke
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.
Open Access
Publisher Correction: 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
The wrong Reporting Summary file was originally published for this Article; it has now been replaced with the correct file.
Open Access
Targeted repair of heart injury by stem cells fused with platelet nanovesicles.
(Nature biomedical engineering, 2018-01) Tang, Junnan; Su, Teng; Huang, Ke; Dinh, Phuong-Uyen; Wang, Zegen; Vandergriff, Adam; Hensley, Michael T; Cores, Jhon; Allen, Tyler; Li, Taosheng; Sproul, Erin; Mihalko, Emily; Lobo, Leonard J; Ruterbories, Laura; Lynch, Alex; Brown, Ashley; Caranasos, Thomas G; Shen, Deliang; Stouffer, George A; Gu, Zhen; Zhang, Jinying; Cheng, Ke
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.
Open Access
Tumor cell-derived exosomes home to their cells of origin and can be used as Trojan horses to deliver cancer drugs.
(Theranostics, 2020-01) Qiao, Li; Hu, Shiqi; Huang, Ke; Su, Teng; Li, Zhenhua; Vandergriff, Adam; Cores, Jhon; Dinh, Phuong-Uyen; Allen, Tyler; Shen, Deliang; Liang, Hongxia; Li, Yongjun; Cheng, Ke
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.

Browsing by Author "Shen, Deliang"

Results Per Page

Sort Options