{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,16]],"date-time":"2026-09-16T11:02:57Z","timestamp":1789556577828,"version":"build-2803163510"},"reference-count":66,"publisher":"SAGE Publications","issue":"5","license":[{"start":{"date-parts":[[2025,8,23]],"date-time":"2025-08-23T00:00:00Z","timestamp":1755907200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.sagepub.com\/page\/policies\/text-and-data-mining-license"}],"content-domain":{"domain":["journals.sagepub.com"],"crossmark-restriction":true},"short-container-title":["J Endovasc Ther"],"published-print":{"date-parts":[[2026,10]]},"abstract":"<jats:p>Peripheral artery disease (PAD) is a chronic vascular condition, and patients in the advanced stages typically do not respond favorably to interventional or surgical approaches. Recent advancements in Wharton\u2019s jelly-derived mesenchymal stem cells (WJ-MSCs) fundamental research have produced promising data in the context of PAD management. As recent pilot studies have suggested WJ-MSCs efficacy in patients with end-stage PAD who lack alternative treatment option, WJ-MSCs may offer a novel therapeutic strategy for managing end-stage PAD. The abundance, ease of isolation, and absence of ethical concerns associated with WJ-MSCs facilitate their potential clinical use. However, randomized, appropriately powered clinical trials are necessary to comprehensively assess their safety and effectiveness. This review aims to summarize the molecular and cellular mechanisms underlying the emerging role of WJ-MSCs in critical limb ischemia.<\/jats:p>\n                  <jats:sec>\n                    <jats:title>Clinical Impact<\/jats:title>\n                    <jats:p>This review establishes Wharton\u2019s Jelly MSCs (WJ-MSCs) as a paradigm-shifting therapy for end-stage critical limb ischemia (CLI).This review pioneers a translational roadmap for WJ-MSCs in CLI by integrating molecular mechanisms, preclinical models, and clinical outcomes. It uniquely identifies anatomic sourcing heterogeneity as a critical efficacy variable and proposes combination therapy with revascularization.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1177\/15266028251361770","type":"journal-article","created":{"date-parts":[[2025,8,23]],"date-time":"2025-08-23T13:19:31Z","timestamp":1755955171000},"page":"2232-2242","update-policy":"https:\/\/doi.org\/10.1177\/sage-journals-update-policy","source":"Crossref","is-referenced-by-count":1,"title":["Application of Wharton\u2019s Jelly Mesenchymal Stem Cells in Critical Limb Ischemia"],"prefix":"10.1177","volume":"33","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-3619-1289","authenticated-orcid":false,"given":"Hao","family":"Liang","sequence":"first","affiliation":[{"name":"Department of Vascular Surgery, Tianjin Medical University General Hospital, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0008-5508-886X","authenticated-orcid":false,"given":"Bin","family":"Zhao","sequence":"additional","affiliation":[{"name":"Department of Vascular Surgery, Tianjin Medical University General Hospital, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuanyuan","family":"Ren","sequence":"additional","affiliation":[{"name":"Department of Otolaryngology, Tianjin Medical University General Hospital, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2878-2169","authenticated-orcid":false,"given":"Peng","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Vascular Surgery, Tianjin Medical University General Hospital, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9074-6452","authenticated-orcid":false,"given":"Xiangchen","family":"Dai","sequence":"additional","affiliation":[{"name":"Department of Vascular Surgery, Tianjin Medical University General Hospital, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"179","published-online":{"date-parts":[[2025,8,23]]},"reference":[{"key":"e_1_3_2_2_2","doi-asserted-by":"publisher","DOI":"10.1186\/s13287-022-03148-9"},{"key":"e_1_3_2_3_2","doi-asserted-by":"publisher","DOI":"10.1161\/CIR.0000000000001005"},{"key":"e_1_3_2_4_2","doi-asserted-by":"publisher","DOI":"10.1007\/s11886-013-0447-2"},{"key":"e_1_3_2_5_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jvs.2014.12.006"},{"key":"e_1_3_2_6_2","doi-asserted-by":"publisher","DOI":"10.1002\/stem.2751"},{"issue":"3","key":"e_1_3_2_7_2","first-page":"177","article-title":"Is revascularization and limb salvage always the treatment for critical limb ischemia?","volume":"45","author":"Nehler MR","year":"2004","unstructured":"Nehler MR, Peyton BD. Is revascularization and limb salvage always the treatment for critical limb ischemia? J Cardiovasc Surg. 2004;45(3):177-184.","journal-title":"J Cardiovasc Surg"},{"key":"e_1_3_2_8_2","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2019.01151"},{"key":"e_1_3_2_9_2","doi-asserted-by":"publisher","DOI":"10.1155\/2013\/589139"},{"key":"e_1_3_2_10_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbmt.2007.08.048"},{"key":"e_1_3_2_11_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0143-4004(97)90071-0"},{"key":"e_1_3_2_12_2","doi-asserted-by":"publisher","DOI":"10.3389\/fcell.2023.1211217"},{"key":"e_1_3_2_13_2","doi-asserted-by":"publisher","DOI":"10.1634\/stemcells.2007-0439"},{"key":"e_1_3_2_14_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.exphem.2009.02.003"},{"key":"e_1_3_2_15_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.pmrj.2014.10.016"},{"key":"e_1_3_2_16_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.cll.2013.11.003"},{"key":"e_1_3_2_17_2","doi-asserted-by":"publisher","DOI":"10.3390\/ijms23063346"},{"key":"e_1_3_2_18_2","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCRESAHA.115.307611"},{"key":"e_1_3_2_19_2","doi-asserted-by":"publisher","DOI":"10.3389\/fphar.2020.613780"},{"key":"e_1_3_2_20_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.immuni.2017.09.008"},{"key":"e_1_3_2_21_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2011.04.005"},{"key":"e_1_3_2_22_2","doi-asserted-by":"publisher","DOI":"10.3389\/fcvm.2017.00086"},{"key":"e_1_3_2_23_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41577-021-00584-1"},{"key":"e_1_3_2_24_2","doi-asserted-by":"publisher","DOI":"10.1007\/s00109-017-1575-8"},{"key":"e_1_3_2_25_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.reth.2020.03.008"},{"key":"e_1_3_2_26_2","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCRESAHA.115.306361"},{"key":"e_1_3_2_27_2","doi-asserted-by":"publisher","DOI":"10.1038\/ni.3002"},{"key":"e_1_3_2_28_2","doi-asserted-by":"publisher","DOI":"10.1155\/2019\/3548917"},{"key":"e_1_3_2_29_2","doi-asserted-by":"publisher","DOI":"10.3109\/14653240903493417"},{"issue":"2","key":"e_1_3_2_30_2","first-page":"145","article-title":"Growth suppression effect of human mesenchymal stem cells from bone marrow, adipose tissue, and Wharton\u2019s jelly of umbilical cord on PBMCs","volume":"19","author":"Ayatollahi M","year":"2016","unstructured":"Ayatollahi M, Talaei-Khozani T, Razmkhah M. Growth suppression effect of human mesenchymal stem cells from bone marrow, adipose tissue, and Wharton\u2019s jelly of umbilical cord on PBMCs. Iran J Basic Med Sci. 2016;19(2):145-153.","journal-title":"Iran J Basic Med Sci"},{"key":"e_1_3_2_31_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.cellimm.2012.06.010"},{"key":"e_1_3_2_32_2","doi-asserted-by":"publisher","DOI":"10.1186\/scrt442"},{"key":"e_1_3_2_33_2","doi-asserted-by":"publisher","DOI":"10.3727\/096368915X688182"},{"key":"e_1_3_2_34_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.ebiom.2019.06.016"},{"key":"e_1_3_2_35_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0009016"},{"key":"e_1_3_2_36_2","doi-asserted-by":"publisher","DOI":"10.1634\/stemcells.2007-1028"},{"key":"e_1_3_2_37_2","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCULATIONAHA.112.000324"},{"key":"e_1_3_2_38_2","doi-asserted-by":"publisher","DOI":"10.1155\/2017\/9824698"},{"key":"e_1_3_2_39_2","doi-asserted-by":"publisher","DOI":"10.1155\/2015\/430847"},{"key":"e_1_3_2_40_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.0300-9475.2004.01483.x"},{"key":"e_1_3_2_41_2","doi-asserted-by":"publisher","DOI":"10.1002\/eji.200636416"},{"key":"e_1_3_2_42_2","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2004-02-0586"},{"key":"e_1_3_2_43_2","doi-asserted-by":"publisher","DOI":"10.1038\/emm.2013.135"},{"key":"e_1_3_2_44_2","doi-asserted-by":"publisher","DOI":"10.1155\/2018\/8429042"},{"key":"e_1_3_2_45_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.cellimm.2017.11.010"},{"key":"e_1_3_2_46_2","doi-asserted-by":"publisher","DOI":"10.1055\/s-0040-1713422"},{"key":"e_1_3_2_47_2","doi-asserted-by":"publisher","DOI":"10.1186\/s13287-022-03201-7"},{"key":"e_1_3_2_48_2","doi-asserted-by":"publisher","DOI":"10.2174\/0113862073314685240514050119"},{"key":"e_1_3_2_49_2","doi-asserted-by":"publisher","DOI":"10.1186\/scrt336"},{"key":"e_1_3_2_50_2","doi-asserted-by":"publisher","DOI":"10.4252\/wjsc.v16.i7.742"},{"key":"e_1_3_2_51_2","doi-asserted-by":"publisher","DOI":"10.1186\/s12916-015-0399-z"},{"key":"e_1_3_2_52_2","doi-asserted-by":"publisher","DOI":"10.2174\/011573403X372908250117092252"},{"key":"e_1_3_2_53_2","doi-asserted-by":"publisher","DOI":"10.1007\/s00441-023-03854-7"},{"key":"e_1_3_2_54_2","doi-asserted-by":"publisher","DOI":"10.1089\/scd.2009.0485"},{"key":"e_1_3_2_55_2","doi-asserted-by":"publisher","DOI":"10.3109\/14653249.2011.605119"},{"key":"e_1_3_2_56_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0072604"},{"key":"e_1_3_2_57_2","doi-asserted-by":"publisher","DOI":"10.1186\/s13287-017-0494-5"},{"key":"e_1_3_2_58_2","doi-asserted-by":"publisher","DOI":"10.1186\/s13287-022-03009-5"},{"key":"e_1_3_2_59_2","doi-asserted-by":"publisher","DOI":"10.3390\/ijms20235859"},{"key":"e_1_3_2_60_2","doi-asserted-by":"publisher","DOI":"10.1186\/s13287-020-02027-5"},{"key":"e_1_3_2_61_2","doi-asserted-by":"publisher","DOI":"10.3390\/ijms22042045"},{"key":"e_1_3_2_62_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.biocel.2012.12.001"},{"key":"e_1_3_2_63_2","doi-asserted-by":"publisher","DOI":"10.1089\/scd.2012.0445"},{"key":"e_1_3_2_64_2","doi-asserted-by":"publisher","DOI":"10.1002\/stem.2920"},{"key":"e_1_3_2_65_2","doi-asserted-by":"publisher","DOI":"10.3390\/ijms20184632"},{"key":"e_1_3_2_66_2","doi-asserted-by":"publisher","DOI":"10.5114\/aic.2022.120963"},{"key":"e_1_3_2_67_2","doi-asserted-by":"publisher","DOI":"10.1186\/s13287-023-03427-z"}],"container-title":["Journal of Endovascular Therapy"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/journals.sagepub.com\/doi\/pdf\/10.1177\/15266028251361770","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/journals.sagepub.com\/doi\/full-xml\/10.1177\/15266028251361770","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/journals.sagepub.com\/doi\/pdf\/10.1177\/15266028251361770","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,9,16]],"date-time":"2026-09-16T10:13:52Z","timestamp":1789553632000},"score":1,"resource":{"primary":{"URL":"https:\/\/journals.sagepub.com\/doi\/10.1177\/15266028251361770"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,8,23]]},"references-count":66,"journal-issue":{"issue":"5","published-print":{"date-parts":[[2026,10]]}},"alternative-id":["10.1177\/15266028251361770"],"URL":"https:\/\/doi.org\/10.1177\/15266028251361770","relation":{},"ISSN":["1526-6028","1545-1550"],"issn-type":[{"value":"1526-6028","type":"print"},{"value":"1545-1550","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,8,23]]}}}