{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,15]],"date-time":"2026-01-15T01:25:47Z","timestamp":1768440347844,"version":"3.49.0"},"reference-count":29,"publisher":"MDPI AG","issue":"5","license":[{"start":{"date-parts":[[2020,5,6]],"date-time":"2020-05-06T00:00:00Z","timestamp":1588723200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000901","name":"Juvenile Diabetes Research Foundation International","doi-asserted-by":"publisher","award":["3-PDF-2018-594-A-N and 3-SRA-2016-255-S-B"],"award-info":[{"award-number":["3-PDF-2018-594-A-N and 3-SRA-2016-255-S-B"]}],"id":[{"id":"10.13039\/100000901","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Biomolecules"],"abstract":"<jats:p>Islet transplantation into subcutaneous polymer scaffolds has shown to successfully induce normoglycemia in type 1 diabetes models. Vascularization of these scaffolds is imperative for optimal control of glucose levels. We studied the effect of the vascular stimulator hydrogen sulfide (H2S) on the degree of vascularization of a scaffold and the role of the immune system in this process. Scaffolds were subcutaneously implanted in immunocompetent C57BL\/6 and immunocompromised nude mice. Mice received twice-daily intraperitoneal injections of the fast-releasing H2S donor sodium hydrosulfide (NaHS, 25 or 50 \u03bcmol\/kg) or saline for 28 days. After 63 days the vascular network was analyzed by histology and gene expression. Here we showed that the vascularization of a subcutaneous scaffold in nude mice was significantly impaired by H2S treatment. Both the CD31 gene and protein expression were reduced in these scaffolds compared to the saline-treated controls. In C57BL\/6 mice, the opposite was found, the vascularization of the scaffold was significantly increased by H2S. The mRNA expression of the angiogenesis marker CD105 was significantly increased compared to the controls as well as the number of CD31 positive blood vessels. In conclusion, the immune system plays an important role in the H2S mediated effect on vascularization of subcutaneous scaffolds.<\/jats:p>","DOI":"10.3390\/biom10050722","type":"journal-article","created":{"date-parts":[[2020,5,7]],"date-time":"2020-05-07T04:46:07Z","timestamp":1588826767000},"page":"722","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["The Effect of a Fast-Releasing Hydrogen Sulfide Donor on Vascularization of Subcutaneous Scaffolds in Immunocompetent and Immunocompromised Mice"],"prefix":"10.3390","volume":"10","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-9714-1779","authenticated-orcid":false,"given":"Alexandra M.","family":"Smink","sequence":"first","affiliation":[{"name":"Department of Pathology and Medical Biology, University Medical Center Groningen, University of Groningen, 9713 GZ Groningen, The Netherlands"},{"name":"Department of Surgery, University of California Irvine, Orange, CA 92868, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Avid","family":"Najdahmadi","sequence":"additional","affiliation":[{"name":"Department of Chemical Engineering and Materials Science, University of California Irvine, Irvine, CA 92617, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7793-394X","authenticated-orcid":false,"given":"Michael","family":"Alexander","sequence":"additional","affiliation":[{"name":"Department of Surgery, University of California Irvine, Orange, CA 92868, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Shiri","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Surgery, University of California Irvine, Orange, CA 92868, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Samuel","family":"Rodriquez","sequence":"additional","affiliation":[{"name":"Department of Surgery, University of California Irvine, Orange, CA 92868, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6670-1577","authenticated-orcid":false,"given":"Harry","family":"van Goor","sequence":"additional","affiliation":[{"name":"Department of Pathology and Medical Biology, University Medical Center Groningen, University of Groningen, 9713 GZ Groningen, The Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jan-Luuk","family":"Hillebrands","sequence":"additional","affiliation":[{"name":"Department of Pathology and Medical Biology, University Medical Center Groningen, University of Groningen, 9713 GZ Groningen, The Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Elliot","family":"Botvinick","sequence":"additional","affiliation":[{"name":"Department of Surgery, University of California Irvine, Orange, CA 92868, USA"},{"name":"Department of Chemical Engineering and Materials Science, University of California Irvine, Irvine, CA 92617, USA"},{"name":"Department of Biomedical Engineering, University of California Irvine, Irvine, CA 92617, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jonathan R. T.","family":"Lakey","sequence":"additional","affiliation":[{"name":"Department of Surgery, University of California Irvine, Orange, CA 92868, USA"},{"name":"Department of Biomedical Engineering, University of California Irvine, Irvine, CA 92617, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9618-2408","authenticated-orcid":false,"given":"Paul","family":"de Vos","sequence":"additional","affiliation":[{"name":"Department of Pathology and Medical Biology, University Medical Center Groningen, University of Groningen, 9713 GZ Groningen, The Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2020,5,6]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"268","DOI":"10.1038\/nrendo.2016.178","article-title":"Clinical pancreatic islet transplantation","volume":"13","author":"Shapiro","year":"2016","journal-title":"Nat. Rev. Endocrinol."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"227","DOI":"10.1111\/tri.12919","article-title":"Intraportal islet transplantation: The impact of the liver microenvironment","volume":"30","author":"Delaune","year":"2017","journal-title":"Transpl. Int."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"1357","DOI":"10.2337\/db12-1553","article-title":"Toward Engineering a Novel Transplantation Site for Human Pancreatic Islets","volume":"62","author":"Smink","year":"2013","journal-title":"Diabetes"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"20","DOI":"10.1016\/j.coph.2018.07.007","article-title":"Pluripotent stem cell replacement approaches to treat type 1 diabetes","volume":"43","author":"Pellegrini","year":"2018","journal-title":"Curr. Opin. Pharmacol."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"e112","DOI":"10.1097\/TP.0000000000001663","article-title":"The Efficacy of a Prevascularized, Retrievable Poly(D,L,-lactide-co-epsilon-caprolactone) Subcutaneous Scaffold as Transplantation Site for Pancreatic Islets","volume":"101","author":"Smink","year":"2017","journal-title":"Transplantation"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"149","DOI":"10.1097\/SLA.0000000000001919","article-title":"A Retrievable, Efficacious Polymeric Scaffold for Subcutaneous Transplantation of Rat Pancreatic Islets","volume":"266","author":"Smink","year":"2017","journal-title":"Ann. Surg."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"81","DOI":"10.3109\/03009734.2016.1164769","article-title":"Pancreatic islet blood flow and its measurement","volume":"121","author":"Jansson","year":"2016","journal-title":"Upsala J. Med Sci."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"748","DOI":"10.1096\/fj.15-273805","article-title":"Cell rearrangement in transplanted human islets","volume":"30","author":"Lavallard","year":"2015","journal-title":"FASEB J."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"634","DOI":"10.1089\/ars.2017.7096","article-title":"Beyond a Gasotransmitter: Hydrogen Sulfide and Polysulfide in Cardiovascular Health and Immune Response","volume":"27","author":"Yuan","year":"2017","journal-title":"Antioxidants Redox Signal."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"29","DOI":"10.1016\/j.cardiores.2007.05.026","article-title":"The novel proangiogenic effect of hydrogen sulfide is dependent on Akt phosphorylation","volume":"76","author":"Cai","year":"2007","journal-title":"Cardiovasc. Res."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"21972","DOI":"10.1073\/pnas.0908047106","article-title":"Hydrogen sulfide is an endogenous stimulator of angiogenesis","volume":"106","author":"Papapetropoulos","year":"2009","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_12","unstructured":"(2020, January 21). Image J, Available online: https:\/\/imagej.nih.gov\/ij\/."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"54","DOI":"10.1016\/j.biomaterials.2018.04.047","article-title":"Design of a vascularized synthetic poly(ethylene glycol) macroencapsulation device for islet transplantation","volume":"172","author":"Weaver","year":"2018","journal-title":"Biomaterials"},{"key":"ref_14","unstructured":"(2018, February 14). Prism\u2014GraphPad. Available online: https:\/\/www.graphpad.com\/scientific-software\/prism\/."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"S75","DOI":"10.33549\/physiolres.933138","article-title":"In Vivo Vascularization of Anisotropic Channeled Porous Polylactide-Based Capsules for Islet Transplantation: The Effects of Scaffold Architecture and Implantation Site","volume":"64","author":"Kasoju","year":"2015","journal-title":"Physiol. Res."},{"key":"ref_16","doi-asserted-by":"crossref","unstructured":"Masuda, J., Shigehiro, T., Matsumoto, T., Satoh, A., Mizutani, A., Umemura, C., Saito, S., Kijihira, M., Takayama, E., and Seno, A. (2018). Cytokine Expression and Macrophage Localization in Xenograft and Allograft Tumor Models Stimulated with Lipopolysaccharide. Int. J. Mol. Sci., 19.","DOI":"10.20944\/preprints201803.0224.v1"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"251","DOI":"10.1016\/j.immuni.2015.07.017","article-title":"Hydrogen Sulfide Promotes Tet1- and Tet2-Mediated Foxp3 Demethylation to Drive Regulatory T Cell Differentiation and Maintain Immune Homeostasis","volume":"43","author":"Yang","year":"2015","journal-title":"Immunity"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"86","DOI":"10.1016\/j.smim.2007.11.004","article-title":"Foreign body reaction to biomaterials","volume":"20","author":"Anderson","year":"2007","journal-title":"Semin. Immunol."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"4320","DOI":"10.4049\/jimmunol.181.6.4320","article-title":"Endogenous hydrogen sulfide regulates inflammatory response by activating the ERK pathway in polymicrobial sepsis","volume":"181","author":"Zhang","year":"2008","journal-title":"J. Immunol."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"1322","DOI":"10.1189\/jlb.1006599","article-title":"Hydrogen sulfide induces the synthesis of proinflammatory cytokines in human monocyte cell line U937 via the ERK-NF-kappaB pathway","volume":"81","author":"Zhi","year":"2007","journal-title":"J. Leukoc. Biol."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"499","DOI":"10.1038\/srep00499","article-title":"Hydrogen sulfide and resolution of acute inflammation: A comparative study utilizing a novel fluorescent probe","volume":"2","author":"Dufton","year":"2012","journal-title":"Sci. Rep."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"1084","DOI":"10.1177\/1535370216650293","article-title":"Monocytes and macrophages in tissue repair: Implications for immunoregenerative biomaterial design","volume":"241","author":"Ogle","year":"2016","journal-title":"Exp. Biol. Med."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"112","DOI":"10.1186\/s13287-020-01607-9","article-title":"Mechanical load-induced H2S production by periodontal ligament stem cells activates M1 macrophages to promote bone remodeling and tooth movement via STAT1","volume":"11","author":"He","year":"2020","journal-title":"Stem Cell Res. Ther."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"24272","DOI":"10.18632\/oncotarget.24917","article-title":"Macrophage inflammatory factors promote epithelial-mesenchymal transition in breast cancer","volume":"9","author":"Bednarczyk","year":"2018","journal-title":"Oncotarget"},{"key":"ref_25","doi-asserted-by":"crossref","unstructured":"Bir, S.C., Kolluru, G., McCarthy, P., Shen, X., Pardue, S., Pattillo, C.B., and Kevil, C.G. (2012). Hydrogen Sulfide Stimulates Ischemic Vascular Remodeling Through Nitric Oxide Synthase and Nitrite Reduction Activity Regulating Hypoxia Inducible Factor 1\u03b1 and Vascular Endothelial Growth Factor\u2013Dependent Angiogenesis. J. Am. Hear. Assoc., 1.","DOI":"10.1161\/JAHA.112.004093"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"1924","DOI":"10.1016\/j.jvs.2018.08.172","article-title":"Effects of a novel hydrogen sulfide prodrug in a porcine model of acute limb ischemia","volume":"69","author":"Rushing","year":"2019","journal-title":"J. Vasc. Surg."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"1077","DOI":"10.1161\/CIRCHEARTFAILURE.113.000299","article-title":"Hydrogen sulfide attenuates cardiac dysfunction after heart failure via induction of angiogenesis","volume":"6","author":"Polhemus","year":"2013","journal-title":"Circ. Hear. Fail."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"2451","DOI":"10.1096\/fj.12-226415","article-title":"Polysulfides are possible H 2 S-derived signaling molecules in rat brain","volume":"27","author":"Kimura","year":"2013","journal-title":"FASEB J."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"1284","DOI":"10.1038\/aps.2013.127","article-title":"Hydrogen sulfide and translational medicine","volume":"34","author":"Guo","year":"2013","journal-title":"Acta Pharmacol. Sin."}],"container-title":["Biomolecules"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2218-273X\/10\/5\/722\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,13]],"date-time":"2025-10-13T13:32:45Z","timestamp":1760362365000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2218-273X\/10\/5\/722"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2020,5,6]]},"references-count":29,"journal-issue":{"issue":"5","published-online":{"date-parts":[[2020,5]]}},"alternative-id":["biom10050722"],"URL":"https:\/\/doi.org\/10.3390\/biom10050722","relation":{},"ISSN":["2218-273X"],"issn-type":[{"value":"2218-273X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2020,5,6]]}}}