{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,18]],"date-time":"2026-02-18T12:14:21Z","timestamp":1771416861418,"version":"3.50.1"},"reference-count":114,"publisher":"MDPI AG","issue":"4","license":[{"start":{"date-parts":[[2026,2,18]],"date-time":"2026-02-18T00:00:00Z","timestamp":1771372800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>An ancient evolutionary regenerative mechanism of injured myocardium in vertebrates has been conserved in zebrafish, urodeles (salamander, newt, and axolotl) and neonatal mice. This innate regenerative mechanism is characterized by extensive migration of pro-regenerative macrophages into the injured myocardium and non-immune activation of parts of the complement system. Loss of regenerative activity in neonatal mice within a few days after birth implies that it is suppressed and replaced by fibrotic repair and scar formation. Fibrosis prevents ventricular wall rupture following myocardial infarction (MI), but it compromises contractility and can lead to heart failure and premature death. Reactivation of the suppressed regenerative mechanism in post-MI adult mice may be feasible by localized immune activation of the complement system, resulting in extensive recruitment of pro-regenerative macrophages into the injured myocardium, recapitulating neonatal mechanisms. Localized complement activation can be achieved by a new method of harnessing the natural anti-Gal antibody, which constitutes ~1% of human immunoglobulins and binds the carbohydrate antigen \u201c\u03b1-gal epitope\u201d. \u03b1-Gal nanoparticles (small liposomes presenting multiple \u03b1-gal epitopes) bind anti-Gal when administered into reperfused myocardium post-MI in anti-Gal-producing mice, thereby inducing localized complement activation. In this novel approach, macrophages recruited into the ischemic myocardium by complement cleavage chemotactic peptides, and binding anti-Gal-coated \u03b1-gal nanoparticles, polarize to become pro-regenerative macrophages that produce pro-regenerative cytokines and recruit stem cells. This process results in near-complete regeneration of the injured myocardium within 14 days. Future evaluation of this novel approach in larger animal models will help in determining whether trans-endocardial delivery by catheter of \u03b1-gal nanoparticles into ischemic myocardium warrants clinical application in acute MI.<\/jats:p>","DOI":"10.3390\/ijms27041950","type":"journal-article","created":{"date-parts":[[2026,2,18]],"date-time":"2026-02-18T11:45:58Z","timestamp":1771415158000},"page":"1950","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Lessons of Macrophage-Associated Heart Regeneration in Fish, Amphibians, and Neonatal Mice, Applied to Adult Mice: A Perspective on \u03b1-Gal Nanoparticles"],"prefix":"10.3390","volume":"27","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-4264-8801","authenticated-orcid":false,"given":"Uri","family":"Galili","sequence":"first","affiliation":[{"name":"Department of Medicine, Rush University Medical Center, Chicago, IL 60612, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Gary L.","family":"Schaer","sequence":"additional","affiliation":[{"name":"Department of Medicine, Rush University Medical Center, Chicago, IL 60612, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2026,2,18]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"2188","DOI":"10.1126\/science.1077857","article-title":"Heart regeneration in zebrafish","volume":"298","author":"Poss","year":"2002","journal-title":"Science"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"11889","DOI":"10.1073\/pnas.1834204100","article-title":"Activation of Notch signaling pathway precedes heart regeneration in zebrafish","volume":"100","author":"Raya","year":"2003","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"607","DOI":"10.1016\/j.cell.2006.08.052","article-title":"A dynamic epicardial injury response supports progenitor cell activity during zebrafish heart regeneration","volume":"127","author":"Lepilina","year":"2006","journal-title":"Cell"},{"key":"ref_4","doi-asserted-by":"crossref","unstructured":"Begeman, I.J., and Kang, J. (2018). Transcriptional Programs and Regeneration Enhancers Underlying Heart Regeneration. J. Cardiovasc. Dev. Dis., 6.","DOI":"10.3390\/jcdd6010002"},{"key":"ref_5","doi-asserted-by":"crossref","unstructured":"Potts, H.G., Stockdale, W.T., and Moersteeg, M.T.M. (2021). Unlocking the Secrets of the Regenerating Fish Heart: Comparing Regenerative Models to Shed Light on Successful Regeneration. J. Cardiovasc. Dev. Dis., 8.","DOI":"10.3390\/jcdd8010004"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"146242","DOI":"10.1016\/j.gene.2022.146242","article-title":"Reconstruction of regulatory network predicts transcription factors driving the dynamics of zebrafish heart regeneration","volume":"819","author":"Nunes","year":"2022","journal-title":"Gene"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"e25605","DOI":"10.7554\/eLife.25605","article-title":"Reciprocal analyses in zebrafish and medaka reveal that harnessing the immune response promotes cardiac regeneration","volume":"6","author":"Lai","year":"2017","journal-title":"ELife"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"1357","DOI":"10.1093\/cvr\/cvz221","article-title":"Specific macrophage populations promote both cardiac scar deposition and subsequent resolution in adult zebrafish","volume":"116","author":"Bevan","year":"2020","journal-title":"Cardiovasc. Res."},{"key":"ref_9","doi-asserted-by":"crossref","unstructured":"Luz, R.B.D.S., Paula, A.G.P., Czaikovski, A.P., Nunes, B.S.F., De Lima, J.D., Paredes, L.C., Bastos, T.S.B., Richardson, R., and Braga, T.T. (2025). Macrophages and cardiac lesion in zebrafish: What can single-cell RNA sequencing reveal?. Front. Cardiovasc. Med., 12.","DOI":"10.3389\/fcvm.2025.1570582"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"1512","DOI":"10.1016\/j.devcel.2022.05.014","article-title":"Macrophages trigger cardiomyocyte proliferation by increasing epicardial vegfaa expression during larval zebrafish heart regeneration","volume":"57","author":"Bruton","year":"2022","journal-title":"Dev. Cell."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"160102","DOI":"10.1098\/rsob.160102","article-title":"Distinct effects of inflammation on preconditioning and regeneration of the adult zebrafish heart","volume":"6","author":"Bise","year":"2016","journal-title":"Open Biol."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"3823","DOI":"10.1038\/s41467-025-59169-4","article-title":"Border-zone cardiomyocytes and macrophages regulate extracellular matrix remodeling to promote cardiomyocyte protrusion during cardiac regeneration","volume":"6","author":"Constanty","year":"2025","journal-title":"Nat. Commun."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"2152","DOI":"10.1161\/CIRCULATIONAHA.117.030801","article-title":"Complement Receptor C5aR1 Plays an Evolutionarily Conserved Role in Successful Cardiac Regeneration","volume":"137","author":"Natarajan","year":"2018","journal-title":"Circulation"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"9415","DOI":"10.1073\/pnas.1300290110","article-title":"Macrophages are required for adult salamander limb regeneration","volume":"110","author":"Godwin","year":"2013","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"67","DOI":"10.1016\/j.ydbio.2011.03.021","article-title":"Recapitulation of developmental cardiogenesis governs the morphological and functional regeneration of adult newt hearts following injury","volume":"354","author":"Witman","year":"2011","journal-title":"Dev. Biol."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"22","DOI":"10.1038\/s41536-017-0027-y","article-title":"Heart regeneration in the salamander relies on macrophage-mediated control of fibroblast activation and the extracellular landscape","volume":"2","author":"Godwin","year":"2017","journal-title":"NPJ Regen. Med."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"1078","DOI":"10.1126\/science.1200708","article-title":"Transient regenerative potential of the neonatal mouse heart","volume":"331","author":"Porrello","year":"2011","journal-title":"Science"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"966","DOI":"10.18632\/aging.100526","article-title":"Complete cardiac regeneration in a mouse model of myocardial infarction","volume":"4","author":"Haubner","year":"2012","journal-title":"Aging"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"2798","DOI":"10.1161\/CIRCULATIONAHA.117.031542","article-title":"Early Regenerative Capacity in the Porcine Heart","volume":"138","author":"Ye","year":"2018","journal-title":"Circulation"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"2809","DOI":"10.1161\/CIRCULATIONAHA.118.034886","article-title":"Regenerative potential of neonatal porcine hearts","volume":"138","author":"Zhu","year":"2018","journal-title":"Circulation"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"1382","DOI":"10.1172\/JCI72181","article-title":"Macrophages are required for neonatal heart regeneration","volume":"124","author":"Aurora","year":"2014","journal-title":"J. Clin. Investig."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"2213","DOI":"10.1016\/j.jacc.2018.08.2149","article-title":"The macrophage in cardiac homeostasis and disease: JACC macrophage in CVD series (Part 4)","volume":"72","author":"Lavine","year":"2018","journal-title":"J. Am. Coll. Cardiol."},{"key":"ref_23","first-page":"16","article-title":"Regenerative healing in fetal skin: A review of the literature","volume":"53","author":"Wilgus","year":"2007","journal-title":"Ostomy Wound Manag."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"128","DOI":"10.1016\/j.tcm.2012.07.008","article-title":"Turning back the cardiac regenerative clock: Lessons from the neonate","volume":"22","author":"Mahmoud","year":"2012","journal-title":"Trends Cardiovasc. Med."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1111\/imm.12110","article-title":"Anti-Gal: An abundant human natural antibody of multiple pathogeneses and clinical benefits","volume":"140","author":"Galili","year":"2013","journal-title":"Immunology"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"91","DOI":"10.1161\/CIRCRESAHA.116.303577","article-title":"The Biological Basis for Cardiac Repair After Myocardial Infarction: From Inflammation to Fibrosis","volume":"119","author":"Prabhu","year":"2016","journal-title":"Circ. Res."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"3037","DOI":"10.1084\/jem.20070885","article-title":"The healing myocardium sequentially mobilizes two monocyte subsets with divergent and complementary functions","volume":"204","author":"Nahrendorf","year":"2007","journal-title":"J. Exp. Med."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"1066","DOI":"10.1161\/ATVBAHA.114.304652","article-title":"Monocytes in myocardial infarction","volume":"35","author":"Dutta","year":"2015","journal-title":"Arter. Arterioscler. Thromb. Vasc. Biol."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"2151","DOI":"10.1172\/JCI85782","article-title":"Alternatively activated macrophages determine repair of the infarcted adult murine heart","volume":"126","author":"Shiraishi","year":"2016","journal-title":"J. Clin. Investig."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"738","DOI":"10.1056\/NEJM199909023411006","article-title":"Cutaneous wound healing","volume":"341","author":"Singer","year":"1999","journal-title":"N. Engl. J. Med."},{"key":"ref_31","doi-asserted-by":"crossref","unstructured":"Ferrini, A., Stevens, M.M., Sattler, S., and Rosenthal, N. (2019). Toward Regeneration of the Heart: Bioengineering Strategies for Immunomodulation. Front. Cardiovasc. Med., 6.","DOI":"10.3389\/fcvm.2019.00026"},{"key":"ref_32","doi-asserted-by":"crossref","unstructured":"Bongiovanni, C., Sacchi, F., Da Pra, S., Pantano, E., Miano, C., Morelli, M.B., and D\u2019Uva, G. (2021). Reawakening the Intrinsic Cardiac Regenerative Potential: Molecular Strategies to Boost Dedifferentiation and Proliferation of Endogenous Cardiomyocytes. Front. Cardiovasc. Med., 8.","DOI":"10.3389\/fcvm.2021.750604"},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"6","DOI":"10.1038\/s41536-025-00394-2","article-title":"Revitalizing the heart: Strategies and tools for cardiomyocyte regeneration post-myocardial infarction","volume":"10","author":"Bois","year":"2025","journal-title":"NPJ Regen. Med."},{"key":"ref_34","doi-asserted-by":"crossref","unstructured":"Galili, U., Zhu, Z., Chen, J., Goldufsky, J.W., and Schaer, G.L. (2021). Near Complete Repair after Myocardial Infarction in Adult Mice by Altering the Inflammatory Response with Intramyocardial Injection of \u03b1-Gal Nanoparticles. Front. Cardiovasc. Med., 8.","DOI":"10.3389\/fcvm.2021.719160"},{"key":"ref_35","doi-asserted-by":"crossref","unstructured":"Debuque, R.J., Hart, A.J., Johnson, G.H., Rosenthal, N.A., and Godwin, J.W. (2021). Identification of the Adult Hematopoietic Liver as the Primary Reservoir for the Recruitment of Pro-regenerative Macrophages Required for Salamander Limb Regeneration. Front. Cell Dev. Biol., 9.","DOI":"10.3389\/fcell.2021.750587"},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"416","DOI":"10.1016\/j.smim.2016.03.009","article-title":"Molecular features of macrophage activation","volume":"27","author":"Schultze","year":"2015","journal-title":"Semin. Immunol."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"18","DOI":"10.1038\/ni.3325","article-title":"The role of the local environment and epigenetics in shaping macrophage identity and their effect on tissue homeostasis","volume":"17","author":"Amit","year":"2016","journal-title":"Nat. Immunol."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"239","DOI":"10.1016\/j.burns.2009.04.002","article-title":"Accelerated healing of skin burns by anti-Gal\/\u03b1-gal liposomes interaction","volume":"36","author":"Galili","year":"2010","journal-title":"Burns"},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"4422","DOI":"10.4049\/jimmunol.1002324","article-title":"Rapid recruitment and activation of macrophages by anti-Gal\/\u03b1-Gal liposome interaction accelerates wound healing","volume":"186","author":"Wigglesworth","year":"2011","journal-title":"J. Immunol."},{"key":"ref_40","doi-asserted-by":"crossref","unstructured":"Galili, U., Li, J., and Schaer, G.L. (2024). Regeneration in Mice of Injured Skin, Heart, and Spinal Cord by \u03b1-Gal Nanoparticles Recapitulates Regeneration in Amphibians. Nanomaterials, 14.","DOI":"10.3390\/nano14080730"},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"2331","DOI":"10.4049\/jimmunol.170.5.2331","article-title":"Expression of complement 3 and complement 5 in newt limb and lens regeneration","volume":"170","author":"Kimura","year":"2003","journal-title":"J. Immunol."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"913","DOI":"10.1084\/jem.20030374","article-title":"The proinflammatory mediators C3a and C5a are essential for liver regeneration","volume":"198","author":"Strey","year":"2003","journal-title":"J. Exp. Med."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"2479","DOI":"10.4049\/jimmunol.166.4.2479","article-title":"A novel role of complement: Mice deficient in the fifth component of complement (C5) exhibit impaired liver regeneration","volume":"166","author":"Mastellos","year":"2001","journal-title":"J. Immunol."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"1519","DOI":"10.1084\/jem.160.5.1519","article-title":"A unique natural human IgG antibody with anti-\u03b1-galactosyl specificity","volume":"160","author":"Galili","year":"1984","journal-title":"J. Exp. Med."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"2828","DOI":"10.4049\/jimmunol.142.8.2828","article-title":"Immunogenic Gal alpha 1\u20143Gal carbohydrate epitopes are present on pathogenic American Trypanosoma and Leishmania","volume":"142","author":"Avila","year":"1989","journal-title":"J. Immunol."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"501","DOI":"10.1097\/00007890-199708150-00021","article-title":"Heterogeneity of human anti-pig natural antibodies cross- reactive with the Gal(\u03b11,3)Galactose epitope","volume":"64","author":"McMorrow","year":"1997","journal-title":"Transplantation"},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"116","DOI":"10.1023\/A:1020506617105","article-title":"Immunochemical properties of anti-Gal\u03b11-3Gal antibodies after sensitization with xenogeneic tissues","volume":"19","author":"Yu","year":"1999","journal-title":"J. Clin. Immunol."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"81","DOI":"10.3390\/biochem1020008","article-title":"Purification and Characterization of Antibodies Directed against the \u03b1-Gal Epitope","volume":"1","author":"Zappe","year":"2021","journal-title":"BioChem."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"573","DOI":"10.1084\/jem.162.2.573","article-title":"Human natural anti-\u03b1-galactosyl IgG. II. The specific recognition of \u03b1[1,3]-linked galactose residues","volume":"162","author":"Galili","year":"1985","journal-title":"J. Exp. Med."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"419","DOI":"10.1084\/jem.166.2.419","article-title":"Circulating antibodies to mouse laminin in Chagas disease, American cutaneous leishmaniasis, and normal individuals recognize terminal galactosyl [\u03b11-3]-galactose epitopes","volume":"166","author":"Towbin","year":"1987","journal-title":"J. Exp. Med."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"599","DOI":"10.1093\/glycob\/6.6.599","article-title":"Molecular mimicry in the recognition of glycosphingolipids by Gal\u03b13Gal\u03b24GlcNAc\u03b2-binding Clostridium difficile toxin A, human natural anti-\u03b1-galactosyl IgG and the monoclonal antibody Gal-13: Characterization of a binding-active human glycosphingolipid, non-identical with the animal receptor","volume":"6","author":"Teneberg","year":"1996","journal-title":"Glycobiology"},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"350","DOI":"10.1034\/j.1399-3089.2002.01094.x","article-title":"Human serum-induced porcine endothelial cell E-selectin expression is associated with IgG3 and IgM anti-Gal antibodies","volume":"9","author":"Saethre","year":"2002","journal-title":"Xenotransplantation"},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"125","DOI":"10.1128\/cdli.2.2.125-131.1995","article-title":"Human secretions contain IgA, IgG and IgM anti-Gal (anti-\u03b1-galactosyl) antibodies","volume":"2","author":"Hamadeh","year":"1995","journal-title":"Clin. Diagnos. Lab. Immunol."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"1730","DOI":"10.1128\/iai.56.7.1730-1737.1988","article-title":"Interaction between human natural anti-\u03b1-galactosyl immunoglobulin G and bacteria of the human flora","volume":"56","author":"Galili","year":"1988","journal-title":"Infect. Immun."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"6215","DOI":"10.1128\/IAI.70.11.6215-6222.2002","article-title":"Induction of cytolytic anti-Gal antibodies in \u03b1-1,3-galactosyltransferase gene knockout mice by oral inoculation with Escherichia coli O86:B7 bacteria","volume":"70","author":"Posekany","year":"2002","journal-title":"Infect. Immun."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"15","DOI":"10.1034\/j.1399-3089.2001.00082.x","article-title":"Removal of bowel aerobic gram-negative bacteria is more effective than immunosuppression with cyclophosphamide and steroids to decrease natural \u03b1-galactosyl IgG antibodies","volume":"8","author":"Blanco","year":"2001","journal-title":"Xenotransplantation"},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"1277","DOI":"10.1016\/j.cell.2014.10.053","article-title":"Gut Microbiota Elicits a Protective Immune Response against Malaria Transmission","volume":"159","author":"Yilmaz","year":"2014","journal-title":"Cell"},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"1700","DOI":"10.1016\/S0021-9258(19)44247-6","article-title":"Enzymatic synthesis of blood group related pentaglycosyl ceramide by an \u03b1-galactosyltransferase","volume":"248","author":"Basu","year":"1973","journal-title":"J. Biol. Chem."},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"5387","DOI":"10.1016\/S0021-9258(19)69212-4","article-title":"An \u03b1-D-galactosyltransferase in Ehrlich ascites tumor cells: Biosynthesis and characterization n of a trisaccharide (\u03b1-D-galacto(1-3)-N-acetyllactosamine)","volume":"256","author":"Blake","year":"1981","journal-title":"J. Biol. Chem."},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"523","DOI":"10.1111\/j.1432-1033.1983.tb07598.x","article-title":"Identification and characterization of an UDP-Gal: N-acetyllactosaminide alpha-1,3-D-galactosyltransferase in calf thymus","volume":"134","author":"Blanken","year":"1983","journal-title":"Eur. J. Biochem."},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"17755","DOI":"10.1016\/S0021-9258(19)77900-9","article-title":"Man, apes, and Old-World monkeys differ from other mammals in the expression of \u03b1-galactosyl epitopes on nucleated cells","volume":"263","author":"Galili","year":"1988","journal-title":"J. Biol. Chem."},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"8227","DOI":"10.1073\/pnas.86.21.8227","article-title":"Isolation of a cDNA encoding murine UDP galactose: \u00dfD-galactosyl-1,4-N-acetyl-D-glucosaminide \u03b11,3-galactosyltransferase: Expression cloning by gene transfer","volume":"86","author":"Larsen","year":"1989","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"14290","DOI":"10.1016\/S0021-9258(18)71676-1","article-title":"Bovine \u03b11-3galactosyltransferase: Isolation and characterization of a cDNA clone. Identification of homologous sequences in human genomic DNA","volume":"264","author":"Joziasse","year":"1989","journal-title":"J. Biol. Chem."},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"7401","DOI":"10.1073\/pnas.88.16.7401","article-title":"Gene sequences suggest inactivation of \u03b11-3 galactosyltransferase in catarrhines after the divergence of apes from monkeys","volume":"88","author":"Galili","year":"1991","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"7055","DOI":"10.1016\/S0021-9258(19)39258-0","article-title":"Frameshift and nonsense mutations in a human genomic sequence homologous to a murine UDP-Gal:\u03b2-D-Gal [1,4]-D-GlcNAc \u03b1[1,3]-galactosyltransferase cDNA","volume":"265","author":"Larsen","year":"1990","journal-title":"J. Biol. Chem."},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"785","DOI":"10.1093\/glycob\/cwf087","article-title":"A complete 1,3-galactosyltransferase gene is present in the human genome and partially transcribed","volume":"12","author":"Giordanengo","year":"2002","journal-title":"Glycobiology"},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"1369","DOI":"10.1073\/pnas.84.5.1369","article-title":"Evolutionary relationship between the anti-Gal antibody and the Gal\u03b11-3Gal epitope in primates","volume":"84","author":"Galili","year":"1987","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"148","DOI":"10.1034\/j.1399-3089.2002.1o058.x","article-title":"Anti-Gal \u03b11-3Gal IgM and IgG antibody levels in sera of humans and old world non-human primates","volume":"9","author":"Teranishi","year":"2002","journal-title":"Xenotransplantation"},{"key":"ref_69","first-page":"559","article-title":"Identification of carbohydrate structures which bind human anti-porcine antibodies: Implication for discordant xenografting in man","volume":"24","author":"Good","year":"1992","journal-title":"Transplant. Proc."},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"198","DOI":"10.1016\/0966-3274(93)90047-C","article-title":"Identification of a-galactosyl and other carbohydrate epitopes that are bound by human anti-pig antibodies: Relevance to discordant xenografting in man","volume":"1","author":"Cooper","year":"1993","journal-title":"Transpl. Immunol."},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"480","DOI":"10.1016\/0167-5699(93)90261-I","article-title":"Interaction of the natural anti-Gal antibody with a-galactosyl epitopes: A major obstacle for xenotransplantation in humans","volume":"14","author":"Galili","year":"1993","journal-title":"Immunol. Today"},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"11391","DOI":"10.1073\/pnas.90.23.11391","article-title":"Anti-pig IgM antibodies in human serum react predominantly with Gal (\u03b1l-3)Gal epitopes","volume":"90","author":"Sandrin","year":"1993","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"98","DOI":"10.1111\/j.1432-2277.1996.tb00862.x","article-title":"The reducing end of a-Gal oligosaccharides contributes to their efficiency in blocking natural antibodies of human and baboon sera","volume":"9","author":"Neethling","year":"1996","journal-title":"Transpl. Int."},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"5500","DOI":"10.4049\/jimmunol.154.10.5500","article-title":"Cardiac xenografts between primate species provide evidence for the importance of the a-galactosyl determinant in hyperacute rejection","volume":"154","author":"Collins","year":"1995","journal-title":"J. Immunol."},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"346","DOI":"10.1097\/00007890-199802150-00009","article-title":"Intravenous infusion of Gala1-3Gal oligosaccharides in baboon delays hyperacute rejection of porcine heart xenografts","volume":"56","author":"Simon","year":"1998","journal-title":"Transplantation"},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"172","DOI":"10.1097\/00007890-199801270-00005","article-title":"Removal of anti-porcine natural antibodies from human and nonhuman primate plasma in vitro and in vivo by a Gal\u03b21-3Gal\u03b214Glc-R immunoaffinity column","volume":"65","author":"Xu","year":"1998","journal-title":"Transplantation"},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"2753","DOI":"10.1016\/j.molimm.2009.04.027","article-title":"The role of the anaphylatoxins in health and disease","volume":"46","author":"Klos","year":"2009","journal-title":"Mol. Immunol."},{"key":"ref_78","doi-asserted-by":"crossref","first-page":"312","DOI":"10.1038\/s41422-023-00779-2","article-title":"Mechanism of activation and biased signaling in complement receptor C5aR1","volume":"33","author":"Feng","year":"2023","journal-title":"Cell Res."},{"key":"ref_79","doi-asserted-by":"crossref","first-page":"114156","DOI":"10.1016\/j.bcp.2020.114156","article-title":"Pharmacological characterisation of small molecule C5aR1 inhibitors in human cells reveals biased activities for signaling and function","volume":"180","author":"Li","year":"2020","journal-title":"Biochem. Pharmacol."},{"key":"ref_80","doi-asserted-by":"crossref","unstructured":"Wang, X., Iyer, A., Lyons, A.B., K\u00f6rner, H., and Wei, W. (2019). Emerging Roles for G-protein Coupled Receptors in Development and Activation of Macrophages. Front. Immunol., 10.","DOI":"10.3389\/fimmu.2019.02031"},{"key":"ref_81","doi-asserted-by":"crossref","first-page":"181","DOI":"10.1146\/annurev.cellbio.12.1.181","article-title":"Fc receptors and their interactions with immunoglobulins","volume":"12","author":"Raghavan","year":"1996","journal-title":"Annu. Rev. Cell Dev. Biol."},{"key":"ref_82","doi-asserted-by":"crossref","first-page":"1093","DOI":"10.1189\/jlb.0804439","article-title":"The coordination of signaling during Fc receptor-mediated phagocytosis","volume":"76","author":"Swanson","year":"2004","journal-title":"J. Leukoc. Biol."},{"key":"ref_83","doi-asserted-by":"crossref","unstructured":"Galili, U., Goldufsky, J.W., and Schaer, G.L. (2022). \u03b1-Gal Nanoparticles Mediated Homing of Endogenous Stem Cells for Repair and Regeneration of External and Internal Injuries by Localized Complement Activation and Macrophage Recruitment. Int. J. Mol. Sci., 23.","DOI":"10.3390\/ijms231911490"},{"key":"ref_84","doi-asserted-by":"crossref","first-page":"21437","DOI":"10.1074\/jbc.270.37.21437","article-title":"Oocyte Gal\u03b1,3Gal epitopes implicated in sperm adhesion to the zona pellucida glycoprotein ZP3 are not required for fertilization in the mouse","volume":"270","author":"Thall","year":"1995","journal-title":"J. Biol. Chem."},{"key":"ref_85","doi-asserted-by":"crossref","unstructured":"Mai, X., Wang, N., Zhu, C., Ma, Y., Ma, Z., Yin, L., and Zhou, D. (2025). Genomic Analysis of Glycosyltransferases Responsible for Galactose-\u03b1-1,3-Galactose Epitopes in Streptococcus pneumoniae: Implications for Broadly Protective Vaccination Strategy. Vaccines, 13.","DOI":"10.3390\/vaccines13111148"},{"key":"ref_86","doi-asserted-by":"crossref","first-page":"2638","DOI":"10.1002\/eji.200526146","article-title":"The influence of natural antibody specificity on antigen immunogenicity","volume":"35","author":"Benatuil","year":"2005","journal-title":"Eur. J. Immunol."},{"key":"ref_87","doi-asserted-by":"crossref","first-page":"4676","DOI":"10.4049\/jimmunol.178.7.4676","article-title":"Intra-tumoral injection of \u03b1-gal glycolipids induces xenograft-like destruction and conversion of lesions into endogenous vaccines","volume":"178","author":"Galili","year":"2007","journal-title":"J. Immunol."},{"key":"ref_88","unstructured":"Galili, U. (2018). The Natural Anti-Gal Antibody as Foe Turned Friend in Medicine, Elsevier."},{"key":"ref_89","doi-asserted-by":"crossref","first-page":"406","DOI":"10.1016\/j.ajt.2023.10.020","article-title":"Human leukocyte antigen class I antibody-activated endothelium promotes CD206+ M2 macrophage polarization and MMP9 secretion through TLR4 signaling and P-selectin in a model of antibody-mediated rejection and allograft vasculopathy","volume":"24","author":"Jin","year":"2024","journal-title":"Am. J. Transplant."},{"key":"ref_90","doi-asserted-by":"crossref","first-page":"414","DOI":"10.1161\/CIRCRESAHA.116.309194","article-title":"Abandoning M1\/M2 for a Network Model of Macrophage Function","volume":"119","author":"Nahrendorf","year":"2016","journal-title":"Circ. Res."},{"key":"ref_91","doi-asserted-by":"crossref","first-page":"431","DOI":"10.1038\/s41569-024-01109-8","article-title":"Functional diversity of cardiac macrophages in health and disease","volume":"22","author":"Yang","year":"2025","journal-title":"Nat. Rev. Cardiol."},{"key":"ref_92","doi-asserted-by":"crossref","first-page":"29","DOI":"10.1038\/s41590-018-0272-2","article-title":"Self-renewing resident cardiac macrophages limit adverse remodeling following myocardial infarction","volume":"20","author":"Dick","year":"2019","journal-title":"Nat. Immunol."},{"key":"ref_93","doi-asserted-by":"crossref","first-page":"222","DOI":"10.1038\/nature20173","article-title":"Hypoxia induces heart regeneration in adult mice","volume":"541","author":"Nakada","year":"2017","journal-title":"Nature"},{"key":"ref_94","doi-asserted-by":"crossref","first-page":"e50163","DOI":"10.7554\/eLife.50163","article-title":"Single-cell analysis uncovers that metabolic reprogramming by ErbB2 signaling is essential for cardiomyocyte proliferation in the regenerating heart","volume":"8","author":"Honkoop","year":"2019","journal-title":"Elife"},{"key":"ref_95","doi-asserted-by":"crossref","first-page":"7444","DOI":"10.1038\/s41467-022-35070-2","article-title":"DOT1L regulates chamber-specific transcriptional networks during cardiogenesis and mediates postnatal cell cycle withdrawal","volume":"13","author":"Cattaneo","year":"2022","journal-title":"Nat. Commun."},{"key":"ref_96","doi-asserted-by":"crossref","first-page":"400","DOI":"10.1161\/CIRCRESAHA.115.307778","article-title":"Revisiting Cardiac Cellular Composition","volume":"118","author":"Pinto","year":"2016","journal-title":"Circ. Res."},{"key":"ref_97","doi-asserted-by":"crossref","first-page":"1023","DOI":"10.1161\/CIRCRESAHA.111.243899","article-title":"Importance of myocyte-nonmyocyte interactions in cardiac development and disease","volume":"110","author":"Tian","year":"2012","journal-title":"Circ. Res."},{"key":"ref_98","first-page":"4683","article-title":"Hippo signaling impedes adult heart regeneration","volume":"140","author":"Heallen","year":"2013","journal-title":"Dev. Camb. Engl."},{"key":"ref_99","doi-asserted-by":"crossref","first-page":"eabd6892","DOI":"10.1126\/scitranslmed.abd6892","article-title":"Gene therapy knockdown of Hippo signaling induces cardiomyocyte renewal in pigs after myocardial infarction","volume":"13","author":"Liu","year":"2021","journal-title":"Sci. Transl. Med."},{"key":"ref_100","doi-asserted-by":"crossref","first-page":"617","DOI":"10.1038\/s44161-022-00090-0","article-title":"Glucocorticoid receptor antagonization propels endogenous cardiomyocyte proliferation and cardiac regeneration","volume":"1","author":"Pianca","year":"2022","journal-title":"Nat. Cardiovasc. Res."},{"key":"ref_101","doi-asserted-by":"crossref","first-page":"e12910","DOI":"10.1111\/cpr.12910","article-title":"Progesterone, via yes-associated protein, promotes cardiomyocyte proliferation and cardiac repair","volume":"53","author":"Lan","year":"2020","journal-title":"Cell Prolif."},{"key":"ref_102","doi-asserted-by":"crossref","first-page":"e70871","DOI":"10.1096\/fj.202501226RR","article-title":"Engineering Nanoparticles and Bioscaffolds for Targeted microRNA Delivery in Cardiovascular Regeneration-A Comprehensive Review","volume":"39","author":"Saravanan","year":"2025","journal-title":"FASEB J."},{"key":"ref_103","doi-asserted-by":"crossref","first-page":"2971","DOI":"10.1016\/j.hrthm.2025.05.052","article-title":"MicroRNAs in cardiac arrhythmias: Mechanisms, biomarkers, and therapeutic frontiers","volume":"22","author":"Popat","year":"2025","journal-title":"Heart Rhythm"},{"key":"ref_104","doi-asserted-by":"crossref","unstructured":"Alam, P., Maliken, B.D., Jones, S.M., Ivey, M.J., Wu, Z., Wang, Y., and Kanisicak, O. (2021). Cardiac Remodeling and Repair: Recent Approaches, Advancements, and Future Perspective. Int. J. Mol. Sci., 22.","DOI":"10.3390\/ijms222313104"},{"key":"ref_105","doi-asserted-by":"crossref","first-page":"117582","DOI":"10.1016\/j.lfs.2020.117582","article-title":"Inflammation in myocardial injury- Stem cells as potential immunomodulators for myocardial regeneration and restoration","volume":"250","author":"Vadivel","year":"2020","journal-title":"Life Sci."},{"key":"ref_106","doi-asserted-by":"crossref","first-page":"1089","DOI":"10.1126\/science.1068228","article-title":"Production of \u03b1-1,3-galactosyltransferase knockout pigs by nuclear transfer cloning","volume":"295","author":"Lai","year":"2002","journal-title":"Science"},{"key":"ref_107","doi-asserted-by":"crossref","first-page":"411","DOI":"10.1126\/science.1078942","article-title":"Production of \u03b11,3-galactosyltransferase-deficient pigs","volume":"299","author":"Phelps","year":"2003","journal-title":"Science"},{"key":"ref_108","doi-asserted-by":"crossref","first-page":"15","DOI":"10.1097\/01.TP.0000130487.68051.EB","article-title":"a1,3-Galactosyltransferase gene-knockout miniature swine produce natural cytotoxic anti-Gal antibodies","volume":"78","author":"Dor","year":"2004","journal-title":"Transplantation"},{"key":"ref_109","doi-asserted-by":"crossref","first-page":"305","DOI":"10.1111\/j.1399-3089.2012.00710.x","article-title":"Anti-gal antibodies in a1,3-galactosyltransferase gene-knockout pigs","volume":"19","author":"Fang","year":"2012","journal-title":"Xenotransplantation"},{"key":"ref_110","doi-asserted-by":"crossref","first-page":"346","DOI":"10.1186\/s12935-019-1059-8","article-title":"AGI-134: A fully synthetic \u03b1-Gal glycolipid that converts tumors into in situ autologous vaccines, induces anti-tumor immunity and is synergistic with an anti-PD-1 antibody in mouse melanoma models","volume":"19","author":"Shaw","year":"2019","journal-title":"Cancer Cell. Int."},{"key":"ref_111","doi-asserted-by":"crossref","first-page":"657","DOI":"10.1007\/s10147-012-0434-4","article-title":"Pancreatic carcinoma-specific immunotherapy using synthesised alpha-galactosyl epitope-activated immune responders: Findings from a pilot study","volume":"18","author":"Qiu","year":"2013","journal-title":"Int. J. Clin. Oncol."},{"key":"ref_112","doi-asserted-by":"crossref","first-page":"5260","DOI":"10.3748\/wjg.v17.i48.5260","article-title":"Hepatocellular Carcinoma-specific Immunotherapy with Synthesized \u03b11,3 Galactosyl Epitope-Pulsed Dendritic-cells and Cytokine-Induced Killer Cells","volume":"17","author":"Qiu","year":"2011","journal-title":"World J. Gastroenterol."},{"key":"ref_113","doi-asserted-by":"crossref","first-page":"91","DOI":"10.1016\/j.jcyt.2015.09.012","article-title":"Combination of Cytokine-Induced Killer and Dendritic-cells Pulsed with Antigenic \u03b1-1,3 galactosyl Epitope-Enhanced Lymphoma Cell Membrane for Effective B-Cell Lymphoma Immunotherapy","volume":"18","author":"Qiu","year":"2016","journal-title":"Cytotherapy"},{"key":"ref_114","doi-asserted-by":"crossref","first-page":"1119","DOI":"10.1016\/j.cell.2024.12.010","article-title":"Hyperacute rejection-engineered oncolytic virus for interventional clinical trial in refractory cancer patients","volume":"188","author":"Zhong","year":"2025","journal-title":"Cell"}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/27\/4\/1950\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,2,18]],"date-time":"2026-02-18T11:48:29Z","timestamp":1771415309000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/27\/4\/1950"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,2,18]]},"references-count":114,"journal-issue":{"issue":"4","published-online":{"date-parts":[[2026,2]]}},"alternative-id":["ijms27041950"],"URL":"https:\/\/doi.org\/10.3390\/ijms27041950","relation":{},"ISSN":["1422-0067"],"issn-type":[{"value":"1422-0067","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,2,18]]}}}