@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{cui_tang_hartanto_zhang_bi_dai_qiao_cheng_zhang_2018, title={NIPAM-based Microgel Microenvironment Regulates the Therapeutic Function of Cardiac Stromal Cells}, volume={10}, ISSN={["1944-8244"]}, DOI={10.1021/acsami.8b09757}, abstractNote={To tune the chemical, physical, and mechanical microenvironment for cardiac stromal cells to treat acute myocardial infarction (MI), we prepared a series of thermally responsive microgels with different surface charges (positive, negative, and neutral) and different degrees of hydrophilicity, as well as functional groups (carboxyl, hydroxyl, amino, and methyl). These microgels were used as injectable hydrogels to create an optimized microenvironment for cardiac stromal cells (CSCs). Our results indicated that a hydrophilic and negatively charged microenvironment created from poly( N-isopropylacrylamide- co-itaconic acid) was favorable for maintaining high viability of CSCs, promoting CSC proliferation and facilitating the formation of CSC spheroids. A large number of growth factors, such as vascular endothelial growth factor (VEGF), insulin-like growth factor I (IGF-1), and stromal-derived factor-1 (SDF-1) were released from the spheroids, promoting neonatal rat cardiomyocyte activation and survival. After injecting the poly( N-isopropylacrylamide- co-itaconic acid) microgel into mice, we examined their acute inflammation and T-cell immune reactions. The microgel itself did not elicit obvious immune response. We then injected the same microgel-encapsulated with CSCs into MI mice. The result revealed the treatment-promoted MI heart repair through angiogenesis and inhibition of apoptosis with an improved cell retention rate. This study will open a door for tailoring poly( N-isopropylacrylamide)-based microgel as a delivery vehicle for CSC therapy.}, number={44}, journal={ACS APPLIED MATERIALS & INTERFACES}, author={Cui, Xiaolin and Tang, Junnan and Hartanto, Yusak and Zhang, Jiabin and Bi, Jingxiu and Dai, Sheng and Qiao, Shi Zhang and Cheng, Ke and Zhang, Hu}, year={2018}, month={Nov}, pages={37783–37796} }
 @article{dinh_cores_hensley_vandergriff_tang_allen_caranasos_adler_lobo_cheng_2017, title={Derivation of therapeutic lung spheroid cells from minimally invasive transbronchial pulmonary biopsies}, volume={18}, ISSN={1465-993X}, url={http://dx.doi.org/10.1186/s12931-017-0611-0}, DOI={10.1186/s12931-017-0611-0}, abstractNote={Resident stem and progenitor cells have been identified in the lung over the last decade, but isolation and culture of these cells remains a challenge. Thus, although these lung stem and progenitor cells provide an ideal source for stem-cell based therapy, mesenchymal stem cells (MSCs) remain the most popular cell therapy product for the treatment of lung diseases. Surgical lung biopsies can be the tissue source but such procedures carry a high risk of mortality.In this study we demonstrate that therapeutic lung cells, termed "lung spheroid cells" (LSCs) can be generated from minimally invasive transbronchial lung biopsies using a three-dimensional culture technique. The cells were then characterized by flow cytometry and immunohistochemistry. Angiogenic potential was tested by in-vitro HUVEC tube formation assay. In-vivo bio- distribution of LSCs was examined in athymic nude mice after intravenous delivery.From one lung biopsy, we are able to derive >50 million LSC cells at Passage 2. These cells were characterized by flow cytometry and immunohistochemistry and were shown to represent a mixture of lung stem cells and supporting cells. When introduced systemically into nude mice, LSCs were retained primarily in the lungs for up to 21 days.Here, for the first time, we demonstrated that direct culture and expansion of human lung progenitor cells from pulmonary tissues, acquired through a minimally invasive biopsy, is possible and straightforward with a three-dimensional culture technique. These cells could be utilized in long-term expansion of lung progenitor cells and as part of the development of cell-based therapies for the treatment of lung diseases such as chronic obstructive pulmonary disease (COPD) and idiopathic pulmonary fibrosis (IPF).}, number={1}, journal={Respiratory Research}, publisher={Springer Nature}, author={Dinh, Phuong-Uyen C. and Cores, Jhon and Hensley, M. Taylor and Vandergriff, Adam C. and Tang, Junnan and Allen, Tyler A. and Caranasos, Thomas G. and Adler, Kenneth B. and Lobo, Leonard J. and Cheng, Ke}, year={2017}, month={Jun} }
 @article{luo_tang_nishi_yan_dinh_cores_kudo_zhang_li_cheng_2017, title={Fabrication of Synthetic Mesenchymal Stem Cells for the Treatment of Acute Myocardial Infarction in Mice}, volume={120}, ISSN={0009-7330 1524-4571}, url={http://dx.doi.org/10.1161/CIRCRESAHA.116.310374}, DOI={10.1161/circresaha.116.310374}, abstractNote={
            
              Rationale:
            
            Stem cell therapy faces several challenges. It is difficult to grow, preserve, and transport stem cells before they are administered to the patient. Synthetic analogs for stem cells represent a new approach to overcome these hurdles and hold the potential to revolutionize regenerative medicine.
          }, number={11}, journal={Circulation Research}, publisher={Ovid Technologies (Wolters Kluwer Health)}, author={Luo, Lan and Tang, Junnan and Nishi, Kodai and Yan, Chen and Dinh, Phuong-Uyen and Cores, Jhon and Kudo, Takashi and Zhang, Jinying and Li, Tao-Sheng and Cheng, Ke}, year={2017}, month={May}, pages={1768–1775} }
 @article{jin_liu_tang_zhu_xuan_zhu_wang_zhang_shen_wang_et al._2017, title={Interleukin-18, matrix metalloproteinase-22 and-29 are independent risk factors of human coronary heart disease}, volume={18}, number={8}, journal={Journal of Zhejiang University-Science B}, author={Jin, D. Y. and Liu, C. L. and Tang, J. N. and Zhu, Z. Z. and Xuan, X. X. and Zhu, X. D. and Wang, Y. Z. and Zhang, T. X. and Shen, D. L. and Wang, X. F. and et al.}, year={2017}, pages={685–695} }
 @article{hensley_tang_woodruff_defrancesco_tou_williams_breen_meurs_keene_cheng_et al._2017, title={Intracoronary allogeneic cardiosphere-derived stem cells are safe for use in dogs with dilated cardiomyopathy}, volume={21}, ISSN={1582-1838}, url={http://dx.doi.org/10.1111/jcmm.13077}, DOI={10.1111/jcmm.13077}, abstractNote={Abstract}, number={8}, journal={Journal of Cellular and Molecular Medicine}, publisher={Wiley}, author={Hensley, Michael Taylor and Tang, Junnan and Woodruff, Kathleen and Defrancesco, Teresa and Tou, Sandra and Williams, Christina M. and Breen, Mathew and Meurs, Kathryn and Keene, Bruce and Cheng, Ke and et al.}, year={2017}, month={Mar}, pages={1503–1512} }
 @article{cores_hensley_kinlaw_rikard_dinh_paudel_tang_vandergriff_allen_li_et al._2017, title={Safety and Efficacy of Allogeneic Lung Spheroid Cells in a Mismatched Rat Model of Pulmonary Fibrosis}, volume={6}, ISSN={2157-6564}, url={http://dx.doi.org/10.1002/sctm.16-0374}, DOI={10.1002/sctm.16-0374}, abstractNote={Abstract}, number={10}, journal={STEM CELLS Translational Medicine}, publisher={Wiley}, author={Cores, Jhon and Hensley, M. Taylor and Kinlaw, Kathryn and Rikard, S. Michaela and Dinh, Phuong-Uyen and Paudel, Dipti and Tang, Junnan and Vandergriff, Adam C. and Allen, Tyler A. and Li, Yazhou and et al.}, year={2017}, month={Aug}, pages={1905–1916} }
 @article{tang_shen_caranasos_wang_vandergriff_allen_hensley_dinh_cores_li_et al._2017, title={Therapeutic microparticles functionalized with biomimetic cardiac stem cell membranes and secretome}, volume={8}, ISSN={2041-1723}, url={http://dx.doi.org/10.1038/ncomms13724}, DOI={10.1038/ncomms13724}, abstractNote={Abstract}, number={1}, journal={Nature Communications}, publisher={Springer Science and Business Media LLC}, author={Tang, Junnan and Shen, Deliang and Caranasos, Thomas George and Wang, Zegen and Vandergriff, Adam C. and Allen, Tyler A. and Hensley, Michael Taylor and Dinh, Phuong-Uyen and Cores, Jhon and Li, Tao-Sheng and et al.}, year={2017}, month={Jan} }
 @article{allen_gracieux_talib_tokarz_hensley_cores_vandergriff_tang_de andrade_dinh_et al._2016, title={Angiopellosis as an Alternative Mechanism of Cell Extravasation}, volume={35}, ISSN={1066-5099}, url={http://dx.doi.org/10.1002/stem.2451}, DOI={10.1002/stem.2451}, abstractNote={Abstract}, number={1}, journal={STEM CELLS}, publisher={Wiley}, author={Allen, Tyler A. and Gracieux, David and Talib, Maliha and Tokarz, Debra A. and Hensley, M. Taylor and Cores, Jhon and Vandergriff, Adam and Tang, Junnan and de Andrade, James B.M. and Dinh, Phuong-Uyen and et al.}, year={2016}, month={Jul}, pages={170–180} }
 @article{shen_tang_hensley_li_caranasos_zhang_zhang_cheng_2016, title={Effects of Matrix Metalloproteinases on the Performance of Platelet Fibrin Gel Spiked With Cardiac Stem Cells in Heart Repair}, volume={5}, ISSN={["2157-6580"]}, DOI={10.5966/sctm.2015-0194}, abstractNote={Abstract}, number={6}, journal={STEM CELLS TRANSLATIONAL MEDICINE}, author={Shen, Deliang and Tang, Junnan and Hensley, Michael Taylor and Li, Taosheng and Caranasos, Thomas George and Zhang, Tianxia and Zhang, Jinying and Cheng, Ke}, year={2016}, month={Jun}, pages={793–803} }
 @article{tang_shen_zhang_ler_chengt_2015, title={Bispecific antibodies, nanoparticles and cells: Bringing the right cells to get the job done}, volume={15}, number={9}, journal={Expert Opinion on Biological Therapy}, author={Tang, J. and Shen, D. L. and Zhang, J. Y. and Ler, F. S. L. and Chengt, K.}, year={2015}, pages={1251–1255} }
 @article{hensley_andrade_keene_meurs_tang_wang_caranasos_piedrahita_li_cheng_et al._2015, title={Cardiac regenerative potential of cardiosphere-derived cells from adult dog hearts}, volume={19}, ISSN={1582-1838}, url={http://dx.doi.org/10.1111/jcmm.12585}, DOI={10.1111/jcmm.12585}, abstractNote={Abstract}, number={8}, journal={Journal of Cellular and Molecular Medicine}, publisher={Wiley}, author={Hensley, M. T. and Andrade, J. and Keene, B. and Meurs, Kathryn and Tang, J. N. and Wang, Z. G. and Caranasos, T. G. and Piedrahita, J. and Li, T. S. and Cheng, K. and et al.}, year={2015}, month={Apr}, pages={1805–1813} }
 @article{vandergriff_de andrade_tang_hensley_piedrahita_caranasos_cheng_2015, title={Intravenous Cardiac Stem Cell-Derived Exosomes Ameliorate Cardiac Dysfunction in Doxorubicin Induced Dilated Cardiomyopathy}, volume={2015}, ISSN={1687-966X 1687-9678}, url={http://dx.doi.org/10.1155/2015/960926}, DOI={10.1155/2015/960926}, abstractNote={Despite the efficacy of cardiac stem cells (CSCs) for treatment of cardiomyopathies, there are many limitations to stem cell therapies. CSC-derived exosomes (CSC-XOs) have been shown to be responsible for a large portion of the regenerative effects of CSCs. Using a mouse model of doxorubicin induced dilated cardiomyopathy, we study the effects of systemic delivery of human CSC-XOs in mice. Mice receiving CSC-XOs showed improved heart function via echocardiography, as well as decreased apoptosis and fibrosis. In spite of using immunocompetent mice and human CSC-XOs, mice showed no adverse immune reaction. The use of CSC-XOs holds promise for overcoming the limitations of stem cells and improving cardiac therapies.}, journal={Stem Cells International}, publisher={Hindawi Limited}, author={Vandergriff, Adam C. and de Andrade, James Bizetto Meira and Tang, Junnan and Hensley, M. Taylor and Piedrahita, Jorge A. and Caranasos, Thomas G. and Cheng, Ke}, year={2015}, pages={1–8} }
 @article{andrade_tang_hensley_vandergriff_cores_henry_allen_caranasos_wang_zhang_et al._2015, title={Rapid and Efficient Production of Coronary Artery Ligation and Myocardial Infarction in Mice Using Surgical Clips}, volume={10}, ISSN={["1932-6203"]}, DOI={10.1371/journal.pone.0143221}, abstractNote={Aims The coronary artery ligation model in rodents mimics human myocardial infarction (MI). Normally mechanical ventilation and prolonged anesthesia period are needed. Recently, a method has been developed to create MI by popping-out the heart (without ventilation) followed by immediate suture ligation. Mortality is high due to the time-consuming suture ligation process while the heart is exposed. We sought to improve this method and reduce mortality by rapid coronary ligation using a surgical clip instead of a suture. Methods and Results Mice were randomized into 3 groups: clip MI (CMI), suture MI (SMI), or sham (SHAM). In all groups, heart was manually exposed without intubation through a small incision on the chest wall. Unlike the conventional SMI method, mice in the CMI group received a metal clip on left anterior descending artery (LAD), quickly dispensed by an AutoSuture Surgiclip™. The CMI method took only 1/3 of ligation time of the standard SMI method and improved post-MI survival rate. TTC staining and Masson’s trichrome staining revealed a similar degree of infarct size in the SMI and CMI groups. Echocardiograph confirmed that both SMI and CMI groups had a similar reduction of ejection fraction and fraction shortening over the time. Histological analysis showed that the numbers of CD68+ macrophages and apoptotic cells (TUNEL-positive) are indistinguishable between the two groups. Conclusion This new method, taking only less than 3 minutes to complete, represents an efficient myocardial infarction model in rodents.}, number={11}, journal={PLOS ONE}, author={Andrade, James N. B. M. and Tang, Junnan and Hensley, Michael Taylor and Vandergriff, Adam and Cores, Jhon and Henry, Eric and Allen, Tyler A. and Caranasos, Thomas George and Wang, Zegen and Zhang, Tianxia and et al.}, year={2015}, month={Nov} }