{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,26]],"date-time":"2026-03-26T18:17:06Z","timestamp":1774549026116,"version":"3.50.1"},"reference-count":37,"publisher":"Public Library of Science (PLoS)","issue":"3","license":[{"start":{"date-parts":[[2026,3,26]],"date-time":"2026-03-26T00:00:00Z","timestamp":1774483200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100007601","name":"Horizon 2020","doi-asserted-by":"publisher","award":["874671"],"award-info":[{"award-number":["874671"]}],"id":[{"id":"10.13039\/501100007601","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100018286","name":"Dutch Arthritis Society","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100018286","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["www.plosone.org"],"crossmark-restriction":false},"short-container-title":["PLoS One"],"abstract":"<jats:sec id=\"sec001\">\n                    <jats:title>Objectives<\/jats:title>\n                    <jats:p>Current osteoarthritis treatments are designed to reduce pain and improve mobility instead of promoting the regeneration of cartilage. Cell-based therapies are being developed for the treatment of osteoarthritis. The aim of this study was to assess the cost-effectiveness of mesenchymal stromal cells and extracellular vesicle treatments compared to standard of care for patients with Kellgren-Lawrence stage II knee osteoarthritis in the Netherlands, from a hospital and societal perspective.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec id=\"sec002\">\n                    <jats:title>Design<\/jats:title>\n                    <jats:p>A Markov model was developed to assess the 40-year incremental cost-effectiveness ratio of mesenchymal stromal cells and\/or extracellular vesicle treatments produced by automated or manual production methods, compared to standard of care. Secondary outcomes were amount of total knee replacement and total knee replacement revision surgeries. In addition, one-way sensitivity analyses and scenario analyses were performed.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec id=\"sec003\">\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>The incremental cost-effectiveness ratios from a hospital perspective were -\u20ac10,982.10 for automatically produced mesenchymal stromal cells, -\u20ac9,301.79 for manually produced mesenchymal stromal cells, -\u20ac12,793.17 for automatically produced mesenchymal stromal cells and extracellular vesicle, and -\u20ac11,998.02 for manually produced mesenchymal stromal cells and extracellular vesicle versus standard of care. From the societal perspective incremental cost-effectiveness ratios were \u20ac68,870.58 for automatically produced mesenchymal stromal cells, -\u20ac67,280.27 for manually produced mesenchymal stromal cells, -\u20ac70,771.65 for automatically produced mesenchymal stromal cells and extracellular vesicle, and -\u20ac69,976.50 for manually produced mesenchymal stromal cells and extracellular vesicle versus standard of care. The amount of total knee replacement surgeries per 1,000 patients was 426 for the cell treatment groups, and 609 for the standard of care group, and 19 and 30 total knee replacement revision surgeries, respectively.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec id=\"sec004\">\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>This model, inherent to its assumptions, shows that hiMSC and EV treatments are cheaper and more effective for patients with knee osteoarthritis, from both perspectives. Moreover, they are expected to lower the number of surgeries. These conclusions persist among all scenario analyses.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1371\/journal.pone.0344203","type":"journal-article","created":{"date-parts":[[2026,3,26]],"date-time":"2026-03-26T17:28:07Z","timestamp":1774546087000},"page":"e0344203","update-policy":"https:\/\/doi.org\/10.1371\/journal.pone.corrections_policy","source":"Crossref","is-referenced-by-count":0,"title":["HiMSC and EV derived treatments increase Quality of Life and reduce amount of Knee Replacement Surgeries compared to current standard of care for knee osteoarthritis patients in The Netherlands"],"prefix":"10.1371","volume":"21","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-4760-412X","authenticated-orcid":true,"given":"Iris W. A.","family":"Boot","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Georgina","family":"Shaw","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1459-413X","authenticated-orcid":true,"given":"Yolande F. M.","family":"Ramos","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mary","family":"Murphy","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ingrid","family":"Meulenbelt","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hubertus J. M.","family":"Vrijhoef","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"name":"on behalf of the AutoCRAT consortium","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"340","published-online":{"date-parts":[[2026,3,26]]},"reference":[{"issue":"2","key":"pone.0344203.ref001","first-page":"448","article-title":"Mesenchymal stem cells in osteoarthritis therapy: A review","volume":"13","author":"C Zhu","year":"2021","journal-title":"Am J Transl Res"},{"key":"pone.0344203.ref002","article-title":"Impact of total knee replacement practice: Cost effectiveness analysis of data from the Osteoarthritis Initiative","volume":"356","author":"BS Ferket","year":"2017","journal-title":"BMJ"},{"issue":"10","key":"pone.0344203.ref003","doi-asserted-by":"crossref","first-page":"1147","DOI":"10.1080\/14737167.2023.2260562","article-title":"Burden of osteoarthritis in the Netherlands: A scoping review","volume":"23","author":"C Beaudart","year":"2023","journal-title":"Expert Rev Pharmacoecon Outcomes Res"},{"key":"pone.0344203.ref004","unstructured":"The unrecognised burden of osteoarthritis: unmet needs in Europe. https:\/\/osteoarthritisineurope.eiu.com\/#:~:text=Osteoarthritis%20(OA)%20is%20a%20chronic,million%20years%20lived%20with%20disability. 2024."},{"issue":"1","key":"pone.0344203.ref005","doi-asserted-by":"crossref","first-page":"631","DOI":"10.1186\/s12913-022-08014-1","article-title":"Quality of knee osteoarthritis care in the Netherlands: A survey on the perspective of people with osteoarthritis","volume":"22","author":"JMH Oomen","year":"2022","journal-title":"BMC Health Serv Res"},{"issue":"9","key":"pone.0344203.ref006","doi-asserted-by":"crossref","first-page":"785","DOI":"10.1097\/MLR.0b013e3181e419b1","article-title":"Impact of knee osteoarthritis on health care resource utilization in a US population-based national sample","volume":"48","author":"EA Wright","year":"2010","journal-title":"Med Care"},{"issue":"12","key":"pone.0344203.ref007","doi-asserted-by":"crossref","first-page":"2200","DOI":"10.1007\/s12325-016-0433-3","article-title":"Potential impact of biologically derived hyaluronic acid on quality of life in patients with knee osteoarthritis in the united States","volume":"33","author":"J Rosen","year":"2017","journal-title":"Adv Ther"},{"issue":"8","key":"pone.0344203.ref008","doi-asserted-by":"crossref","DOI":"10.1001\/jamanetworkopen.2019.10223","article-title":"Opioid prescription patterns and risk factors associated with opioid use in the Netherlands","volume":"2","author":"A Bedene","year":"2019","journal-title":"JAMA Netw Open"},{"issue":"1","key":"pone.0344203.ref009","doi-asserted-by":"crossref","first-page":"72","DOI":"10.1186\/s13287-024-03688-2","article-title":"Large-scale bioreactor production of extracellular vesicles from mesenchymal stromal cells for treatment of acute radiation syndrome","volume":"15","author":"JA Kink","year":"2024","journal-title":"Stem Cell Res Ther"},{"key":"pone.0344203.ref010","doi-asserted-by":"crossref","first-page":"918565","DOI":"10.3389\/fimmu.2022.918565","article-title":"Optimization of Mesenchymal Stromal Cell (MSC) Manufacturing Processes for a Better Therapeutic Outcome","volume":"13","author":"ME Fern\u00e1ndez-Santos","year":"2022","journal-title":"Front Immunol"},{"issue":"1","key":"pone.0344203.ref011","doi-asserted-by":"crossref","first-page":"434","DOI":"10.1186\/s13287-022-03117-2","article-title":"Characterizing the secretome of licensed hiPSC-derived MSCs","volume":"13","author":"YFM Ramos","year":"2022","journal-title":"Stem Cell Res Ther"},{"issue":"8","key":"pone.0344203.ref012","doi-asserted-by":"crossref","first-page":"1258","DOI":"10.1016\/j.jval.2023.03.009","article-title":"Frameworks for Health technology assessment at an early stage of product development: A review and roadmap to guide applications","volume":"26","author":"E Rodriguez Llorian","year":"2023","journal-title":"Value Health"},{"key":"pone.0344203.ref013","unstructured":"Unknown. 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