{"corpus_id":46955538,"paper_sha":"125eeebf0b1c4c30b51a8f1c07286957790f0386","doi":"10.1089/ten.tea.2018.0093","arxiv_id":null,"pmid":29882474,"pmcid":null,"mag_id":2806074452,"dblp_id":null,"acl_id":null,"title":"Adipose-Derived Stem Cells in a Resilient In Situ Forming Hydrogel Modulate Macrophage Phenotype","year":2018,"publication_date":"2018-12-01","venue":"Tissue Engineering. Part A","journal":{"name":"Tissue Engineering Part A","pages":"1784 - 1797","volume":"24"},"journal_issn":null,"journal_title":null,"publication_types":["JournalArticle"],"pubmed_pub_types":["Journal Article","Research Support, Non-U.S. Gov't"],"s2_fields_of_study":["Medicine","Chemistry","Engineering"],"reference_count":69,"citation_count":16,"influential_citation_count":1,"is_open_access":false,"arxiv_categories":null,"arxiv_license":null,"arxiv_journal_ref":null,"mesh_headings":[{"d":"Adipocytes","mj":false,"qs":[{"q":"cytology","mj":false,"ui":"Q000166"},{"q":"metabolism","mj":true,"ui":"Q000378"}],"ui":"D017667"},{"d":"Animals","mj":false,"ui":"D000818"},{"d":"Cell Differentiation","mj":true,"ui":"D002454"},{"d":"Cells, Immobilized","mj":false,"qs":[{"q":"cytology","mj":false,"ui":"Q000166"},{"q":"metabolism","mj":false,"ui":"Q000378"},{"q":"transplantation","mj":false,"ui":"Q000637"}],"ui":"D018914"},{"d":"Female","mj":false,"ui":"D005260"},{"d":"Humans","mj":false,"ui":"D006801"},{"d":"Hydrogels","mj":true,"qs":[{"q":"chemistry","mj":false,"ui":"Q000737"},{"q":"pharmacology","mj":false,"ui":"Q000494"}],"ui":"D020100"},{"d":"Macrophages","mj":false,"qs":[{"q":"metabolism","mj":true,"ui":"Q000378"}],"ui":"D008264"},{"d":"Rats","mj":false,"ui":"D051381"},{"d":"Rats, Wistar","mj":false,"ui":"D017208"},{"d":"Stem Cell Transplantation","mj":true,"ui":"D033581"},{"d":"Stem Cells","mj":false,"qs":[{"q":"cytology","mj":false,"ui":"Q000166"},{"q":"metabolism","mj":true,"ui":"Q000378"}],"ui":"D013234"}],"chemicals":[{"n":"Hydrogels","ui":"D020100","reg":"0"}],"comments_corrections":null,"source_flags":5,"s2_open_access_pdf_url":null,"s2_open_access_landing_url":null,"s2_open_access_license":null,"s2_open_access_status":null,"pmc_open_access_pdf_url":null,"pmc_open_access_landing_url":null,"pmc_open_access_license":null,"pmc_open_access_status":null,"unpaywall_open_access_pdf_url":null,"unpaywall_open_access_landing_url":null,"unpaywall_open_access_license":null,"unpaywall_open_access_status":null,"abstract":"Injectable hydrogels have the potential to enhance stem cell-based therapies by improving cell localization, retention, and survival after transplantation. The inflammatory response to both the hydrogel and the encapsulated cells is a critical aspect of this strategy, with macrophages being highly involved in the process of hydrogel remodeling, angiogenesis, and tissue regeneration. As a step toward the development of a cell-based strategy for therapeutic angiogenesis, this work compared the intramuscular injection of allogeneic rat adipose-derived stem/stromal cells (rASCs) in an in situ gelling hydrogel with the injection of the hydrogel alone and rASCs in saline in an immunocompetent rat model by immunohistochemical analysis over 4 weeks. rASCs delivered in the hydrogel were retained intramuscularly at significantly higher densities as compared with cells delivered in saline. The encapsulated rASCs modulated the inflammatory response, promoting CD68+ macrophage recruitment, with the majority of infiltrating cells expressing the M1 marker CCR7, as well as a higher fraction of CD163+ M2c macrophages surrounding the hydrogel. Furthermore, rASCs reduced the initial expression of inducible nitric oxide synthase and promoted arginase-1 expression in the infiltrating macrophages over time, consistent with a shift toward a more proregenerative phenotype. Coincident with the enhanced macrophage infiltration, significantly more CD31+ lumens were observed surrounding and within the hydrogels with rASCs at 2 and 4 weeks as compared with the hydrogels alone. Overall, these results are a promising indication that encapsulated rASCs can have immunomodulatory effects and may enhance angiogenic processes after intramuscular injection, promoting a regenerative macrophage response and blood vessel formation.","claims":[{"public_id":"cl_857fd6185e6922a2e6d481bf61a17dd8","status":"active","text":"Allogeneic rat adipose-derived stem/stromal cells delivered in an in situ gelling hydrogel were retained intramuscularly at significantly higher densities than cells delivered in saline.","confidence":0.98,"contributors":[{"id":1,"public_id":"12632b8b5f","public_label":"Anonymous (12632b8b5f)","roles":["extraction"],"url":"https://sah.borca.ai/u/12632b8b5f"}],"url":"https://sah.borca.ai/claims/cl_857fd6185e6922a2e6d481bf61a17dd8"},{"public_id":"cl_5f26f0960fe16ebbc61478dd9d06dae3","status":"active","text":"Encapsulated rat adipose-derived stem/stromal cells promoted CD68+ macrophage recruitment, with most infiltrating cells expressing the M1 marker CCR7 and a higher fraction of CD163+ M2c macrophages surrounding the hydrogel.","confidence":0.96,"contributors":[{"id":1,"public_id":"12632b8b5f","public_label":"Anonymous (12632b8b5f)","roles":["extraction"],"url":"https://sah.borca.ai/u/12632b8b5f"}],"url":"https://sah.borca.ai/claims/cl_5f26f0960fe16ebbc61478dd9d06dae3"},{"public_id":"cl_5c76a6ee03330dfb72fbf31c4f40418b","status":"active","text":"Hydrogels containing rat adipose-derived stem/stromal cells showed significantly more CD31+ lumens surrounding and within the hydrogels at 2 and 4 weeks than hydrogels alone.","confidence":0.97,"contributors":[{"id":1,"public_id":"12632b8b5f","public_label":"Anonymous (12632b8b5f)","roles":["extraction"],"url":"https://sah.borca.ai/u/12632b8b5f"}],"url":"https://sah.borca.ai/claims/cl_5c76a6ee03330dfb72fbf31c4f40418b"},{"public_id":"cl_e79bf72d18ab610ecec16361b2b760b6","status":"active","text":"Rat adipose-derived stem/stromal cells reduced initial inducible nitric oxide synthase expression and promoted arginase-1 expression in infiltrating macrophages over time, consistent with a shift toward a more proregenerative phenotype.","confidence":0.95,"contributors":[{"id":1,"public_id":"12632b8b5f","public_label":"Anonymous (12632b8b5f)","roles":["extraction"],"url":"https://sah.borca.ai/u/12632b8b5f"}],"url":"https://sah.borca.ai/claims/cl_e79bf72d18ab610ecec16361b2b760b6"}],"concepts":[{"public_id":"co_04ee5cce5e509b7e556795286748bba8","status":"active","name":"CD31+ lumens","description":"Endothelial-lined vessel-like structures identified by CD31 staining.","types":["angiogenesis marker","vascular structure"],"aliases":[],"contributors":[{"id":1,"public_id":"12632b8b5f","public_label":"Anonymous (12632b8b5f)","roles":["extraction"],"url":"https://sah.borca.ai/u/12632b8b5f"}],"url":"https://sah.borca.ai/concepts/co_04ee5cce5e509b7e556795286748bba8"},{"public_id":"co_0c8d4ddf055ed1265cb43ea5237ecb00","status":"active","name":"intramuscular retention","description":"Persistence of injected cells within muscle tissue after transplantation.","types":["outcome"],"aliases":[],"contributors":[{"id":1,"public_id":"12632b8b5f","public_label":"Anonymous (12632b8b5f)","roles":["extraction"],"url":"https://sah.borca.ai/u/12632b8b5f"}],"url":"https://sah.borca.ai/concepts/co_0c8d4ddf055ed1265cb43ea5237ecb00"},{"public_id":"co_2b5551cc65dfcd55940137238b2cddf8","status":"active","name":"CD68+ macrophage recruitment","description":"Accumulation of macrophages identified by CD68 expression at the implantation site.","types":["immune response"],"aliases":[],"contributors":[{"id":1,"public_id":"12632b8b5f","public_label":"Anonymous (12632b8b5f)","roles":["extraction"],"url":"https://sah.borca.ai/u/12632b8b5f"}],"url":"https://sah.borca.ai/concepts/co_2b5551cc65dfcd55940137238b2cddf8"},{"public_id":"co_7450fc9ce682716939db7b938a39b0c1","status":"active","name":"arginase-1","description":"An enzyme used as a marker associated with alternatively activated macrophages.","types":["marker"],"aliases":["Arg1"],"contributors":[{"id":1,"public_id":"12632b8b5f","public_label":"Anonymous (12632b8b5f)","roles":["extraction"],"url":"https://sah.borca.ai/u/12632b8b5f"}],"url":"https://sah.borca.ai/concepts/co_7450fc9ce682716939db7b938a39b0c1"},{"public_id":"co_7a159b4a7f8c115991d5cc242fc676b0","status":"active","name":"inducible nitric oxide synthase","description":"An enzyme used as a marker of inflammatory macrophage activation.","types":["marker"],"aliases":["iNOS"],"contributors":[{"id":1,"public_id":"12632b8b5f","public_label":"Anonymous (12632b8b5f)","roles":["extraction"],"url":"https://sah.borca.ai/u/12632b8b5f"}],"url":"https://sah.borca.ai/concepts/co_7a159b4a7f8c115991d5cc242fc676b0"},{"public_id":"co_a2fe57329dacf6e5a6cd5b5b0694b401","status":"active","name":"proregenerative phenotype","description":"A macrophage activation state associated with tissue repair and regeneration.","types":["phenotype"],"aliases":[],"contributors":[{"id":1,"public_id":"12632b8b5f","public_label":"Anonymous (12632b8b5f)","roles":["extraction"],"url":"https://sah.borca.ai/u/12632b8b5f"}],"url":"https://sah.borca.ai/concepts/co_a2fe57329dacf6e5a6cd5b5b0694b401"},{"public_id":"co_be86eee986a77761c06085214fd1dd1b","status":"active","name":"allogeneic rat adipose-derived stem/stromal cells","description":"Stem/stromal cells isolated from rat adipose tissue and transplanted from a donor of the same species.","types":["cell type"],"aliases":["rASCs"],"contributors":[{"id":1,"public_id":"12632b8b5f","public_label":"Anonymous (12632b8b5f)","roles":["extraction"],"url":"https://sah.borca.ai/u/12632b8b5f"}],"url":"https://sah.borca.ai/concepts/co_be86eee986a77761c06085214fd1dd1b"},{"public_id":"co_c876fecd8dd01434284c86c338d240ca","status":"active","name":"CCR7","description":"A macrophage marker associated with the M1 inflammatory phenotype.","types":["marker"],"aliases":[],"contributors":[{"id":1,"public_id":"12632b8b5f","public_label":"Anonymous (12632b8b5f)","roles":["extraction"],"url":"https://sah.borca.ai/u/12632b8b5f"}],"url":"https://sah.borca.ai/concepts/co_c876fecd8dd01434284c86c338d240ca"},{"public_id":"co_edba8176941cba9420bc88af5a8c2141","status":"active","name":"in situ gelling hydrogel","description":"An injectable hydrogel formulation that gels after administration at the target site.","types":["biomaterial","delivery vehicle"],"aliases":[],"contributors":[{"id":1,"public_id":"12632b8b5f","public_label":"Anonymous (12632b8b5f)","roles":["extraction"],"url":"https://sah.borca.ai/u/12632b8b5f"}],"url":"https://sah.borca.ai/concepts/co_edba8176941cba9420bc88af5a8c2141"},{"public_id":"co_f400649b9df0f0c52d663fc2f8e718a7","status":"active","name":"CD163+ M2c macrophages","description":"A macrophage subset identified by CD163 expression and associated with an M2c phenotype.","types":["immune cell subset"],"aliases":["M2c macrophages"],"contributors":[{"id":1,"public_id":"12632b8b5f","public_label":"Anonymous (12632b8b5f)","roles":["extraction"],"url":"https://sah.borca.ai/u/12632b8b5f"}],"url":"https://sah.borca.ai/concepts/co_f400649b9df0f0c52d663fc2f8e718a7"}],"external_ids":{"DOI":"10.1089/ten.tea.2018.0093","ArXiv":null,"PubMed":29882474,"PubMedCentral":null,"MAG":2806074452,"DBLP":null,"ACL":null},"open_access":{"is_open_access":false,"pdf_url":null,"landing_url":"https://sah.borca.ai/papers/46955538","source":null,"pdf_url_source":null,"license":null,"reason":"pdf_url_not_indexed"},"reference_availability":{"status":"available","references_indexed":true,"full_text_available":false,"full_text_source":null,"count_basis":"semantic_scholar_metadata","extraction_status":"not_applicable","reason":null},"source":{"provider":"episteme2","base_corpus":"semantic_scholar_dump","freshness_mode":"unknown","basis":["semantic_scholar_metadata","postgres_metadata"],"limits":["paper metadata is based on indexed upstream scholarly datasets","claims and concepts are available only for extracted papers","absence of claims or concepts means no extracted graph data is available in this response"],"status":"available","degraded":false,"degraded_reasons":[],"diagnostics":{"status":"available","degraded":false,"degraded_reasons":[],"metadata_status":"available","graph_status":"available","abstract_status":"available"},"source_flags":5},"paper_id":637309,"paper_uid":"519699fa-b047-41fe-95c5-85963daf3007","canonical_identity":{"paper_id":637309,"paper_uid":"519699fa-b047-41fe-95c5-85963daf3007","identity_status":"available","lookup_basis":"semantic_scholar_external_id","compatibility_path":"corpus_id"},"url":"https://sah.borca.ai/papers/46955538"}