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We found evidence that konjac glucomannan\u2013modified silica nanoparticles (KSiNPs) remodeled the spleen into an extracellular matrix (ECM)\u2013rich, immunosuppressive niche to support the survival of syngeneic or xenogeneic islets. Transplanted islets in the remodeled spleens showed improved engraftment, neovascularization, and functionality and restored normoglycemia in streptozotocin (STZ)\u2013induced type 1 diabetic models in the mice and macaques, with stable insulin and C-peptide secretion in mice for 90 days and macaques for 28 days. KSiNP injection and islet transplantation into macaque spleens under B-ultrasound guidance were preclinically feasible. These findings highlight the safety and effectiveness of spleen tissue remodeling in supporting the survival and function of transplanted islets, providing a promising strategy for treating type 1 diabetes mellitus (T1DM).<\/jats:p>","DOI":"10.1126\/scitranslmed.adj9615","type":"journal-article","created":{"date-parts":[[2025,5,21]],"date-time":"2025-05-21T18:00:24Z","timestamp":1747850424000},"update-policy":"https:\/\/doi.org\/10.34133\/aaas_crossmark","source":"Crossref","is-referenced-by-count":12,"title":["Islet transplantation in immunomodulatory nanoparticle\u2013remodeled spleens"],"prefix":"10.1126","volume":"17","author":[{"ORCID":"https:\/\/orcid.org\/0009-0003-3758-787X","authenticated-orcid":true,"given":"Mi","family":"Liu","sequence":"first","affiliation":[{"name":"Oujiang Laboratory (Zhejiang Lab for Regenerative Medicine, Vision and Brain Health), School of Pharmaceutical Science, Department of Wound Healing of the First Affiliated Hospital, Wenzhou Medical University, Wenzhou, 325035, China."},{"name":"State Key Laboratory of Pharmaceutical Biotechnology, School of Life Sciences, Nanjing University, Nanjing, Jiangsu, 210023, China."},{"name":"State Key Laboratory of Quality Research in Chinese Medicine, Institute of Chinese Medical Sciences, University of Macau, Taipa, 999078, Macau SAR, China."},{"name":"Affiliated Cixi Hospital, Wenzhou Medical University, Cixi, 315300, China."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1409-6926","authenticated-orcid":true,"given":"Huiming","family":"Deng","sequence":"additional","affiliation":[{"name":"Oujiang Laboratory (Zhejiang Lab for Regenerative Medicine, Vision and Brain Health), School of Pharmaceutical Science, Department of Wound Healing of the First Affiliated Hospital, Wenzhou Medical University, Wenzhou, 325035, China."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0006-1202-3527","authenticated-orcid":true,"given":"Chunyan","family":"Liu","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Pharmaceutical Biotechnology, School of Life Sciences, Nanjing University, Nanjing, Jiangsu, 210023, China."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2886-560X","authenticated-orcid":true,"given":"Lintao","family":"Wang","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Pharmaceutical Biotechnology, School of Life Sciences, Nanjing University, Nanjing, Jiangsu, 210023, China."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0009-2639-5526","authenticated-orcid":true,"given":"Zhongkai","family":"Liao","sequence":"additional","affiliation":[{"name":"Department of Organ Transplantation, Second Affiliated Hospital of Hainan Medical University, Haikou, 570216, China."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8973-3491","authenticated-orcid":true,"given":"Desheng","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Organ Transplantation, Second Affiliated Hospital of Hainan Medical University, Haikou, 570216, China."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0002-0536-2687","authenticated-orcid":true,"given":"Yan","family":"Chen","sequence":"additional","affiliation":[{"name":"Department of Oncology of the First Affiliated Hospital and Cancer Institute, Hainan Medical University, Haikou, 570102, China."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jianhui","family":"Li","sequence":"additional","affiliation":[{"name":"Division of Hepatobiliary Pancreatic Surgery, Key Laboratory of Combined Multi-organ Transplantation, Ministry of Public Health, First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou 310003, China."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jianhui","family":"Dong","sequence":"additional","affiliation":[{"name":"Institute of Transplantation Medicine, Second Affiliated Hospital of Guangxi Medical University; Guangxi Clinical Research Center for Organ Transplantation; Guangxi Key Laboratory of Organ Donation and Transplantation, Nanning 530007, China."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xuyong","family":"Sun","sequence":"additional","affiliation":[{"name":"Institute of Transplantation Medicine, Second Affiliated Hospital of Guangxi Medical University; Guangxi Clinical Research Center for Organ Transplantation; Guangxi Key Laboratory of Organ Donation and Transplantation, Nanning 530007, China."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9185-9678","authenticated-orcid":true,"given":"Chunming","family":"Wang","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Quality Research in Chinese Medicine, Institute of Chinese Medical Sciences, University of Macau, Taipa, 999078, Macau SAR, China."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5173-689X","authenticated-orcid":true,"given":"Ling","family":"Huang","sequence":"additional","affiliation":[{"name":"School of Hainan Provincial Drug Safety Evaluation Research Center, Hainan Medical University, Haikou, 571199, China."},{"name":"Center for Pharmacovigilance of Hainan Province, Hainan Medical Products Administration, Haikou, 570216, China."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2013-4191","authenticated-orcid":true,"given":"Lei","family":"Dong","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Pharmaceutical Biotechnology, School of Life Sciences, Nanjing University, Nanjing, Jiangsu, 210023, China."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7374-6506","authenticated-orcid":true,"given":"Jian","family":"Xiao","sequence":"additional","affiliation":[{"name":"Oujiang Laboratory (Zhejiang Lab for Regenerative Medicine, Vision and Brain Health), School of Pharmaceutical Science, Department of Wound Healing of the First Affiliated Hospital, Wenzhou Medical University, Wenzhou, 325035, China."}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"221","reference":[{"key":"e_1_3_2_2_2","doi-asserted-by":"publisher","DOI":"10.1038\/nrendo.2016.178"},{"key":"e_1_3_2_3_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJM200007273430401"},{"key":"e_1_3_2_4_2","doi-asserted-by":"publisher","DOI":"10.1097\/01.tp.0000261104.27113.05"},{"key":"e_1_3_2_5_2","doi-asserted-by":"publisher","DOI":"10.1210\/er.2018-00154"},{"key":"e_1_3_2_6_2","doi-asserted-by":"publisher","DOI":"10.3389\/fendo.2021.732431"},{"key":"e_1_3_2_7_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0603909103"},{"key":"e_1_3_2_8_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMc070201"},{"key":"e_1_3_2_9_2","doi-asserted-by":"publisher","DOI":"10.1111\/tri.12919"},{"key":"e_1_3_2_10_2","doi-asserted-by":"publisher","DOI":"10.2337\/db09-0490"},{"key":"e_1_3_2_11_2","doi-asserted-by":"publisher","DOI":"10.1155\/2014\/451035"},{"key":"e_1_3_2_12_2","doi-asserted-by":"publisher","DOI":"10.21037\/atm-20-3519"},{"key":"e_1_3_2_13_2","doi-asserted-by":"publisher","DOI":"10.3389\/fendo.2021.652853"},{"key":"e_1_3_2_14_2","doi-asserted-by":"publisher","DOI":"10.2337\/db10-0205"},{"key":"e_1_3_2_15_2","doi-asserted-by":"publisher","DOI":"10.3346\/jkms.2010.25.2.203"},{"key":"e_1_3_2_16_2","doi-asserted-by":"publisher","DOI":"10.1158\/0008-5472.CAN-05-2787"},{"key":"e_1_3_2_17_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.abh1657"},{"key":"e_1_3_2_18_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41587-020-0430-6"},{"key":"e_1_3_2_19_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41556-018-0271-4"},{"key":"e_1_3_2_20_2","doi-asserted-by":"publisher","DOI":"10.1126\/scitranslmed.abg9170"},{"key":"e_1_3_2_21_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.stem.2023.04.002"},{"key":"e_1_3_2_22_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.stem.2021.10.003"},{"key":"e_1_3_2_23_2","doi-asserted-by":"publisher","DOI":"10.1126\/sciadv.aaz9974"},{"key":"e_1_3_2_24_2","doi-asserted-by":"publisher","DOI":"10.1136\/gutjnl-2021-325018"},{"key":"e_1_3_2_25_2","first-page":"72","article-title":"Efficacy and safety of splenectomy in immune thrombocytopenic purpura: Long-term results of 402 cases","volume":"90","author":"Vianelli N.","year":"2005","unstructured":"N. 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