@article{henry_cores_hensley_anthony_vandergriff_andrade_allen_caranasos_lobo_cheng_2015, title={Adult Lung Spheroid Cells Contain Progenitor Cells and Mediate Regeneration in Rodents With Bleomycin-Induced Pulmonary Fibrosis}, volume={4}, ISSN={["2157-6580"]}, DOI={10.5966/sctm.2015-0062}, abstractNote={Abstract Lung diseases are devastating conditions and ranked as one of the top five causes of mortality worldwide according to the World Health Organization. Stem cell therapy is a promising strategy for lung regeneration. Previous animal and clinical studies have focused on the use of mesenchymal stem cells (from other parts of the body) for lung regenerative therapies. We report a rapid and robust method to generate therapeutic resident lung progenitors from adult lung tissues. Outgrowth cells from healthy lung tissue explants are self-aggregated into three-dimensional lung spheroids in a suspension culture. Without antigenic sorting, the lung spheroids recapitulate the stem cell niche and contain a natural mixture of lung stem cells and supporting cells. In vitro, lung spheroid cells can be expanded to a large quantity and can form alveoli-like structures and acquire mature lung epithelial phenotypes. In severe combined immunodeficiency mice with bleomycin-induced pulmonary fibrosis, intravenous injection of human lung spheroid cells inhibited apoptosis, fibrosis, and infiltration but promoted angiogenesis. In a syngeneic rat model of pulmonary fibrosis, lung spheroid cells outperformed adipose-derived mesenchymal stem cells in reducing fibrotic thickening and infiltration. Previously, lung spheroid cells (the spheroid model) had only been used to study lung cancer cells. Our data suggest that lung spheroids and lung spheroid cells from healthy lung tissues are excellent sources of regenerative lung cells for therapeutic lung regeneration. Significance The results from the present study will lead to future human clinical trials using lung stem cell therapies to treat various incurable lung diseases, including pulmonary fibrosis. The data presented here also provide fundamental knowledge regarding how injected stem cells mediate lung repair in pulmonary fibrosis.}, number={11}, journal={STEM CELLS TRANSLATIONAL MEDICINE}, author={Henry, Eric and Cores, Jhon and Hensley, M. Taylor and Anthony, Shirena and Vandergriff, Adam and Andrade, James B. M. and Allen, Tyler and Caranasos, Thomas G. and Lobo, Leonard J. and Cheng, Ke}, year={2015}, month={Nov}, pages={1265–1274} } @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} } @article{vandergriff_hensley_henry_shen_anthony_zhang_cheng_2014, title={Magnetic targeting of cardiosphere-derived stem cells with ferumoxytol nanoparticles for treating rats with myocardial infarction}, volume={35}, ISSN={["1878-5905"]}, DOI={10.1016/j.biomaterials.2014.06.031}, abstractNote={Stem cell transplantation is a promising therapeutic strategy for acute or chronic ischemic cardiomyopathy. A major limitation to efficacy in cell transplantation is the low efficiency of retention and engraftment, due at least in part to significant early "wash-out" of cells from coronary blood flow and heart contraction. We sought to enhance cell retention and engraftment by magnetic targeting. Human cardiosphere-derived stem cells (hCDCs) were labeled with FDA-approved ferumoxytol nanoparticles Feraheme(®) (F) in the presence of heparin (H) and protamine (P). FHP labeling is nontoxic to hCDCs. FHP-labeled rat CDCs (FHP-rCDCs) were intracoronarily infused into syngeneic rats, with and without magnetic targeting. Magnetic resonance imaging, fluorescence imaging, and quantitative PCR revealed magnetic targeting increased cardiac retention of transplanted FHP-rCDCs. Neither infusion of FHP-rCDCs nor magnetic targeting exacerbated cardiac inflammation or caused iron overload. The augmentation of acute cell retention translated into more attenuated left ventricular remodeling and greater therapeutic benefit (ejection fraction) 3 weeks after treatment. Histology revealed enhanced cell engraftment and angiogenesis in hearts from the magnetic targeting group. FHP labeling is safe to cardiac stem cells and facilitates magnetically-targeted stem cell delivery into the heart which leads to augmented cell engraftment and therapeutic benefit.}, number={30}, journal={BIOMATERIALS}, author={Vandergriff, Adam C. and Hensley, Taylor M. and Henry, Eric T. and Shen, Deliang and Anthony, Shirena and Zhang, Jinying and Cheng, Ke}, year={2014}, month={Oct}, pages={8528–8539} }