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Here, we demonstrate the safety and efficacy of encapsulating human cardiac stem cells (hCSCs) in thermosensitive poly(N-isopropylacrylamine-co-acrylic acid) or P(NIPAM-AA) nanogel in mouse and pig models of myocardial infarction (MI). Unlike xenogeneic hCSCs injected in saline, injection of nanogel-encapsulated hCSCs does not elicit systemic inflammation or local T cell infiltrations in immunocompetent mice. In mice and pigs with acute MI, injection of encapsulated hCSCs preserves cardiac function and reduces scar sizes, whereas injection of hCSCs in saline has an adverse effect on heart healing. In conclusion, thermosensitive nanogels can be used as a stem cell carrier: the porous and convoluted inner structure allows nutrient, oxygen, and secretion diffusion but can prevent the stem cells from being attacked by immune cells.<\/jats:p>","DOI":"10.1021\/acsnano.7b01008","type":"journal-article","created":{"date-parts":[[2017,9,20]],"date-time":"2017-09-20T08:01:06Z","timestamp":1505894466000},"page":"9738-9749","source":"Crossref","is-referenced-by-count":145,"title":["Heart\nRepair Using Nanogel-Encapsulated Human Cardiac\nStem Cells in Mice and Pigs with Myocardial Infarction"],"prefix":"10.1021","volume":"11","author":[{"given":"Junnan","family":"Tang","sequence":"first","affiliation":[{"name":"The First Affiliated Hospital of Zhengzhou University , , , ,","place":["Zhengzhou, Henan, China, 450052"]},{"name":"North Carolina State University , , , ,","place":["Raleigh, North Carolina, United States, 27607"]},{"name":"University of North Carolina at Chapel Hill & North Carolina State University , , , ,","place":["Raleigh, North Carolina, United States, 27607"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5118-0169","authenticated-orcid":true,"given":"Xiaolin","family":"Cui","sequence":"additional","affiliation":[{"name":"The University of Adelaide , , , ,","place":["Adelaide, SA, Australia, 5005"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thomas G.","family":"Caranasos","sequence":"additional","affiliation":[{"name":"University of North Carolina at Chapel Hill , , , ,","place":["Chapel Hill, North Carolina, United States, 27599"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"M. Taylor","family":"Hensley","sequence":"additional","affiliation":[{"name":"North Carolina State University , , , ,","place":["Raleigh, North Carolina, United States, 27607"]},{"name":"University of North Carolina at Chapel Hill & North Carolina State University , , , ,","place":["Raleigh, North Carolina, United States, 27607"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7614-4834","authenticated-orcid":true,"given":"Adam C.","family":"Vandergriff","sequence":"additional","affiliation":[{"name":"North Carolina State University , , , ,","place":["Raleigh, North Carolina, United States, 27607"]},{"name":"University of North Carolina at Chapel Hill & North Carolina State University , , , ,","place":["Raleigh, North Carolina, United States, 27607"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yusak","family":"Hartanto","sequence":"additional","affiliation":[{"name":"The University of Adelaide , , , ,","place":["Adelaide, SA, Australia, 5005"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Deliang","family":"Shen","sequence":"additional","affiliation":[{"name":"The First Affiliated Hospital of Zhengzhou University , , , ,","place":["Zhengzhou, Henan, China, 450052"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hu","family":"Zhang","sequence":"additional","affiliation":[{"name":"The University of Adelaide , , , ,","place":["Adelaide, SA, Australia, 5005"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jinying","family":"Zhang","sequence":"additional","affiliation":[{"name":"The First Affiliated Hospital of Zhengzhou University , , , ,","place":["Zhengzhou, Henan, China, 450052"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ke","family":"Cheng","sequence":"additional","affiliation":[{"name":"North Carolina State University , , , ,","place":["Raleigh, North Carolina, United States, 27607"]},{"name":"University of North Carolina at Chapel Hill & North Carolina State University , , , ,","place":["Raleigh, North Carolina, United States, 27607"]},{"name":"University of North Carolina at Chapel Hill , , , ,","place":["Chapel Hill, North Carolina, United States, 27599"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"316","published-online":{"date-parts":[[2017,9,20]]},"reference":[{"key":"2026090308462987600_cit1","doi-asserted-by":"publisher","first-page":"1847","DOI":"10.1016\/S0140-6736(11)61590-0","article-title":"Cardiac\nStem Cells in Patients with Ischaemic Cardiomyopathy\n(SCIPIO): Initial Results of a Randomised Phase 1 Trial","volume":"378","author":"Bolli","year":"2011","journal-title":"Lancet"},{"key":"2026090308462987600_cit2","doi-asserted-by":"publisher","first-page":"2161","DOI":"10.1016\/j.jacc.2016.01.083","article-title":"Translation of Human-Induced\nPluripotent Stem Cells:\nFrom Clinical Trial in a Dish to Precision Medicine","volume":"67","author":"Sayed","year":"2016","journal-title":"J. Am. Coll. Cardiol."},{"key":"2026090308462987600_cit3","doi-asserted-by":"publisher","first-page":"219","DOI":"10.1016\/S1474-4422(15)00332-4","article-title":"Accelerating Stem Cell Trials for Alzheimer\u2019s Disease","volume":"15","author":"Hunsberger","year":"2016","journal-title":"Lancet Neurol."},{"key":"2026090308462987600_cit4","doi-asserted-by":"publisher","first-page":"160","DOI":"10.1002\/ejhf.434","article-title":"Congestive Heart Failure\nCardiopoietic Regenerative Therapy (CHART-1) Trial Design","volume":"18","author":"Bartunek","year":"2016","journal-title":"Eur. J. Heart Failure"},{"key":"2026090308462987600_cit5","doi-asserted-by":"publisher","first-page":"1386","DOI":"10.1038\/nm.3764","article-title":"An Emerging Consensus on Cardiac\nRegeneration","volume":"20","author":"van Berlo","year":"2014","journal-title":"Nat. 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Heart Lung Transplant."},{"key":"2026090308462987600_cit21","doi-asserted-by":"publisher","first-page":"9290","DOI":"10.1016\/j.biomaterials.2011.08.057","article-title":"The Amelioration\nof Cardiac Dysfunction\nafter Myocardial Infarction by the Injection of Keratin Biomaterials\nDerived from Human Hair","volume":"32","author":"Shen","year":"2011","journal-title":"Biomaterials"},{"key":"2026090308462987600_cit22","doi-asserted-by":"publisher","first-page":"11507","DOI":"10.1073\/pnas.1004097107","article-title":"Injectable\nHydrogel Properties Influence Infarct Expansion\nand Extent of Postinfarction Left Ventricular Remodeling in an Ovine\nModel","volume":"107","author":"Ifkovits","year":"2010","journal-title":"Proc. Natl. Acad. Sci. U. S. A."},{"key":"2026090308462987600_cit23","doi-asserted-by":"publisher","first-page":"163","DOI":"10.1002\/jbm.b.31386","article-title":"Regeneration\nof Ischemic Heart Using\nHyaluronic Acid-Based Injectable Hydrogel","volume":"91B","author":"Yoon","year":"2009","journal-title":"J.\nBiomed. Mater. Res., Part B"},{"key":"2026090308462987600_cit24","doi-asserted-by":"publisher","first-page":"701","DOI":"10.1124\/jpet.114.215798","article-title":"Targeted\nInjection of a Biocomposite Material Alters Macrophage and Fibroblast\nPhenotype and Function Following Myocardial Infarction: Relation to\nLeft Ventricular Remodeling","volume":"350","author":"McGarvey","year":"2014","journal-title":"J. Pharmacol. Exp.\nTher."},{"key":"2026090308462987600_cit25","doi-asserted-by":"publisher","first-page":"1172","DOI":"10.1002\/biot.200700228","article-title":"Recent\nAdvances in Three-dimensional Multicellular\nSpheroid Culture for Biomedical Research","volume":"3","author":"Lin","year":"2008","journal-title":"Biotechnol.\nJ."},{"key":"2026090308462987600_cit26","doi-asserted-by":"publisher","first-page":"1090","DOI":"10.5966\/sctm.2014-0049","article-title":"Concise\nReview: Injectable Biomaterials for The Treatment\nof Myocardial Infarction and Peripheral Artery Disease: Translational\nChallenges and Progress","volume":"3","author":"Ungerleider","year":"2014","journal-title":"Stem Cells Transl.\nMed."},{"key":"2026090308462987600_cit27","doi-asserted-by":"publisher","first-page":"4357","DOI":"10.1016\/j.biomaterials.2009.04.055","article-title":"Synthesis, Characterization and Therapeutic Efficacy\nof a Biodegradable, Thermoresponsive Hydrogel Designed for Application\nin Chronic Infarcted Myocardium","volume":"30","author":"Fujimoto","year":"2009","journal-title":"Biomaterials"},{"key":"2026090308462987600_cit28","doi-asserted-by":"publisher","first-page":"54","DOI":"10.1016\/j.addr.2015.04.021","article-title":"Alginate Biomaterial\nfor the Treatment of Myocardial Infarction:\nProgress, Translational Strategies, and Clinical Outlook: from Ocean\nAlgae to Patient Bedside","volume":"96","author":"Ruvinov","year":"2016","journal-title":"Adv. Drug Delivery\nRev."},{"key":"2026090308462987600_cit29","doi-asserted-by":"publisher","first-page":"e000367","DOI":"10.1161\/JAHA.113.000367","article-title":"Cellular Encapsulation Enhances Cardiac Repair","volume":"2","author":"Levit","year":"2013","journal-title":"J. Am. Heart Assoc."},{"key":"2026090308462987600_cit30","doi-asserted-by":"publisher","first-page":"5317","DOI":"10.1016\/j.biomaterials.2012.04.006","article-title":"Functional Performance\nof Human Cardiosphere-Derived Cells Delivered in an in situ Polymerizable Hyaluronan-Gelatin Hydrogel","volume":"33","author":"Cheng","year":"2012","journal-title":"Biomaterials"},{"key":"2026090308462987600_cit31","doi-asserted-by":"publisher","first-page":"2652","DOI":"10.1021\/ie801449k","article-title":"Noncompetitive Removal of Heavy Metal Ions from Aqueous\nSolutions by Poly [2-(acrylamido)-2-methyl-1-propanesulfonic acid-co-itaconic\nacid] Hydrogel","volume":"48","author":"Cavus","year":"2009","journal-title":"Ind. Eng. Chem. Res."},{"key":"2026090308462987600_cit32","doi-asserted-by":"publisher","first-page":"651","DOI":"10.1039\/C3TB21519A","article-title":"Stimuli-Responsive\nElectrospun Nanofibers from Poly (N-isopropylacrylamide)-co-poly (acrylic\nacid) Copolymer and Polyurethane","volume":"2","author":"Lin","year":"2014","journal-title":"J. Mater.\nChem. B"},{"key":"2026090308462987600_cit33","doi-asserted-by":"publisher","first-page":"774","DOI":"10.1093\/eurheartj\/ehw224","article-title":"The Pathophysiology\nof Acute Myocardial Infarction\nand Strategies of Protection Beyond Reperfusion: a Continual Challenge","volume":"38","author":"Heusch","year":"2017","journal-title":"Eur. Heart J."},{"key":"2026090308462987600_cit34","doi-asserted-by":"publisher","first-page":"810","DOI":"10.1161\/CIRCRESAHA.113.300219","article-title":"Cell Therapy for Heart Failure: a\nComprehensive Overview of Experimental\nand Clinical Studies, Current Challenges, and Future Directions","volume":"113","author":"Sanganalmath","year":"2013","journal-title":"Circ. Res."},{"key":"2026090308462987600_cit35","doi-asserted-by":"publisher","first-page":"306","DOI":"10.1038\/nm.4030","article-title":"Long-Term Glycemic Control\nUsing Polymer-Encapsulated\nHuman Stem Cell-Derived Beta Cells in Immune-competent Mice","volume":"22","author":"Vegas","year":"2016","journal-title":"Nat. Med."},{"key":"2026090308462987600_cit36","doi-asserted-by":"publisher","first-page":"12","DOI":"10.1016\/j.biomaterials.2015.02.075","article-title":"Microcapsules Engineered\nto Support Mesenchymal Stem Cell (MSC) Survival and Proliferation\nEnable Long-term Retention of MSCs in Infarcted Myocardium","volume":"53","author":"Blocki","year":"2015","journal-title":"Biomaterials"},{"key":"2026090308462987600_cit37","doi-asserted-by":"publisher","first-page":"7250","DOI":"10.1039\/c2sm25407g","article-title":"Exploring\nThermal Reversible Hydrogels for Stem Cell Expansion in\nThree-dimensions","volume":"8","author":"Shen","year":"2012","journal-title":"Soft Matter"},{"key":"2026090308462987600_cit38","doi-asserted-by":"publisher","first-page":"73282","DOI":"10.1039\/C6RA11699J","article-title":"A Mechanistic Study\non Tumour Spheroid\nFormation in Thermosensitive Hydrogels: Experiments and Mathematical\nModelling","volume":"6","author":"Cui","year":"2016","journal-title":"RSC Adv."},{"key":"2026090308462987600_cit39","doi-asserted-by":"publisher","first-page":"895","DOI":"10.1016\/S0140-6736(12)60195-0","article-title":"Intracoronary\nCardiosphere-Derived\nCells for Heart Regeneration after Myocardial Infarction (CADUCEUS):\na Prospective, Randomised Phase 1 Trial","volume":"379","author":"Makkar","year":"2012","journal-title":"Lancet"},{"key":"2026090308462987600_cit40","doi-asserted-by":"publisher","first-page":"942","DOI":"10.1016\/j.jacc.2011.11.029","article-title":"Direct\nComparison of Different Stem Cell Types and\nSubpopulations Reveals Superior Paracrine Potency and Myocardial Repair\nEfficacy with Cardiosphere-Derived Cells","volume":"59","author":"Li","year":"2012","journal-title":"J.\nAm. Coll. Cardiol."},{"key":"2026090308462987600_cit41","doi-asserted-by":"publisher","first-page":"2939","DOI":"10.1016\/j.actbio.2009.04.040","article-title":"Bone Marrow Stem Cells\nImplantation with \u03b1-cyclodextrin\/MPEG\u2013PCL\u2013MPEG\nHydrogel Improves Cardiac Function after Myocardial Infarction","volume":"5","author":"Wang","year":"2009","journal-title":"Acta Biomater."},{"key":"2026090308462987600_cit42","doi-asserted-by":"publisher","first-page":"1437","DOI":"10.1089\/ten.tea.2008.0143","article-title":"Functional Improvement of Infarcted Heart by\nCo-Injection\nof Embryonic Stem Cells with Temperature-responsive Chitosan Hydrogel","volume":"15","author":"Lu","year":"2009","journal-title":"Tissue Eng., Part A"},{"key":"2026090308462987600_cit43","doi-asserted-by":"publisher","first-page":"1310","DOI":"10.1111\/j.1582-4934.2011.01409.x","article-title":"Injectable Biodegradable\nHydrogels for Embryonic Stem Cell Transplantation: Improved Cardiac\nRemodelling and Function of Myocardial Infarction","volume":"16","author":"Wang","year":"2012","journal-title":"J. Cell Mol. Med."},{"key":"2026090308462987600_cit44","doi-asserted-by":"publisher","first-page":"e001260","DOI":"10.1161\/JAHA.114.001260","article-title":"Relative Roles\nof CD90 and C-kit to the Regenerative Efficacy of Cardiosphere-Derived\nCells in Humans and in a Mouse Model of Myocardial Infarction","volume":"3","author":"Cheng","year":"2014","journal-title":"J. Am. Heart Assoc."},{"key":"2026090308462987600_cit45","doi-asserted-by":"publisher","first-page":"e0143221","DOI":"10.1371\/journal.pone.0143221","article-title":"Rapid and Efficient\nProduction of Coronary Artery Ligation and Myocardial Infarction in\nMice Using Surgical Clips","volume":"10","author":"Andrade","year":"2015","journal-title":"PLoS One"},{"key":"2026090308462987600_cit46","doi-asserted-by":"publisher","first-page":"1445","DOI":"10.1161\/CIRCRESAHA.110.223925","article-title":"A Novel and Efficient\nModel of Coronary Artery Ligation\nand Myocardial Infarction in the Mouse","volume":"107","author":"Gao","year":"2010","journal-title":"Circ.\nRes."},{"key":"2026090308462987600_cit47","doi-asserted-by":"publisher","first-page":"1570","DOI":"10.1161\/CIRCRESAHA.109.212589","article-title":"Magnetic Targeting Enhances Engraftment and Functional\nBenefit of Iron-Labeled Cardiosphere-Derived Cells in Myocardial Infarction","volume":"106","author":"Cheng","year":"2010","journal-title":"Circ. Res."},{"key":"2026090308462987600_cit48","doi-asserted-by":"publisher","first-page":"13724","DOI":"10.1038\/ncomms13724","article-title":"Therapeutic\nMicroparticles Functionalized with Biomimetic\nCardiac Stem Cell Membranes and Secretome","volume":"8","author":"Tang","year":"2017","journal-title":"Nat.\nCommun."},{"key":"2026090308462987600_cit49","doi-asserted-by":"publisher","first-page":"1768","DOI":"10.1161\/CIRCRESAHA.116.310374","article-title":"Fabrication of Synthetic Mesenchymal\nStem Cells for the Treatment\nof Acute Myocardial Infarction in Mice","volume":"120","author":"Luo","year":"2017","journal-title":"Circ.\nRes."}],"container-title":["ACS Nano"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/pubs.acs.org\/doi\/pdf\/10.1021\/acsnano.7b01008","content-type":"application\/pdf","content-version":"vor","intended-application":"unspecified"},{"URL":"https:\/\/pubs.acs.org\/ancac3\/article-pdf\/11\/10\/9738\/67241149\/acsnano.7b01008.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/pubs.acs.org\/ancac3\/article-pdf\/11\/10\/9738\/67241149\/acsnano.7b01008.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,9,3]],"date-time":"2026-09-03T12:46:38Z","timestamp":1788439598000},"score":1,"resource":{"primary":{"URL":"https:\/\/pubs.acs.org\/ancac3\/article\/11\/10\/9738\/744663\/Heart-Repair-Using-Nanogel-Encapsulated-Human"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2017,9,20]]},"references-count":49,"journal-issue":{"issue":"10","published-online":{"date-parts":[[2017,9,20]]},"published-print":{"date-parts":[[2017,10,24]]}},"URL":"https:\/\/doi.org\/10.1021\/acsnano.7b01008","relation":{},"ISSN":["1936-0851","1936-086X"],"issn-type":[{"value":"1936-0851","type":"print"},{"value":"1936-086X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2017,9,20]]}}}