{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,21]],"date-time":"2025-10-21T15:46:51Z","timestamp":1761061611900,"version":"3.37.3"},"reference-count":31,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2022,3,4]],"date-time":"2022-03-04T00:00:00Z","timestamp":1646352000000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2022,3,4]],"date-time":"2022-03-04T00:00:00Z","timestamp":1646352000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"name":"Organogenesis"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Arthritis Res Ther"],"published-print":{"date-parts":[[2022,12]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec>\n                <jats:title>Background<\/jats:title>\n                <jats:p>Osteoarthritis is a degenerative disease of the knee that affects 250 million people worldwide. Due to the rising incidence of knee replacement and revision surgery, there is a need for a nonsurgical treatment to reduce pain and improve function in patients with knee osteoarthritis. Placental-derived allografts, such as an amniotic suspension allograft (ASA), provide growth factors and cytokines that could potentially modulate the inflammatory environment of osteoarthritis. The purpose of this study was to evaluate the efficacy of ASA in a rat medial meniscal tear (MMT) induced osteoarthritis model through histology, microCT, synovial fluid biomarkers, and behavioral testing.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Methods<\/jats:title>\n                <jats:p>Rats underwent MMT surgery at day \u2212\u20097; at day 0, rats were injected with either ASA, vehicle control, or fibroblast growth factor-18 (FGF18). Behavioral testing, including gait analysis, pain threshold, incapacitance, and knee swelling were evaluated <jats:italic>in-life<\/jats:italic>, along with histology, microCT analysis of cartilage, and synovial fluid testing post-sacrifice. One MMT cohort was sacrificed at day 10, the other at day 21. A third cohort acted as a safety arm and did not receive MMT surgery; these rats were injected with either vehicle control or ASA and evaluated at day 3 and day 21.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Results<\/jats:title>\n                <jats:p>Behavioral testing showed a significant improvement in pain threshold, incapacitance, and gait following an injection of ASA. MicroCT showed significant improvements in cartilage thickness and attenuation at day 10 only, and histology showed no detrimental effects compared to the vehicle control at day 21. Synovial fluid analysis showed a significant increase in anti-inflammatory IL-10. The safety cohort showed no significant differences except for an increase in synovitis at day 21, which could be evidence of a xenogeneic response in this model.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Conclusions<\/jats:title>\n                <jats:p>In this study, an injection of ASA was well tolerated with no adverse events. Improvements in pain and function, along with cartilage properties at day 10, were observed. Increases in anti-inflammatory cytokines was also seen, along with no significant cartilage degeneration at day 21 compared to the vehicle control. This study provides evidence for the use of ASA as a nonsurgical treatment for knee OA.<\/jats:p>\n              <\/jats:sec>","DOI":"10.1186\/s13075-022-02750-9","type":"journal-article","created":{"date-parts":[[2022,3,4]],"date-time":"2022-03-04T13:26:31Z","timestamp":1646400391000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":9,"title":["Amniotic suspension allograft improves pain and function in a rat meniscal tear-induced osteoarthritis model"],"prefix":"10.1186","volume":"24","author":[{"given":"Kelly A.","family":"Kimmerling","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Andreas H.","family":"Gomoll","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jack","family":"Farr","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0047-544X","authenticated-orcid":false,"given":"Katie C.","family":"Mowry","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"297","published-online":{"date-parts":[[2022,3,4]]},"reference":[{"issue":"2","key":"2750_CR1","doi-asserted-by":"publisher","first-page":"312","DOI":"10.1016\/j.berh.2018.10.007","volume":"32","author":"TW O\u2019Neill","year":"2018","unstructured":"O\u2019Neill TW, McCabe PS, McBeth J. Update on the epidemiology, risk factors and disease outcomes of osteoarthritis. Best Pract Res Clin Rheumatol. 2018;32(2):312\u201326 Available from: https:\/\/doi.org\/10.1016\/j.berh.2018.10.007.","journal-title":"Best Pract Res Clin Rheumatol"},{"issue":"11","key":"2750_CR2","doi-asserted-by":"publisher","first-page":"1618","DOI":"10.1016\/j.joca.2019.07.002","volume":"27","author":"X Zhao","year":"2019","unstructured":"Zhao X, Shah D, Gandhi K, Wei W, Dwibedi N, Webster L, et al. Clinical, humanistic, and economic burden of osteoarthritis among noninstitutionalized adults in the United States. Osteoarthr Cartil. 2019;27(11):1618\u201326 Available from: https:\/\/doi.org\/10.1016\/j.joca.2019.07.002.","journal-title":"Osteoarthr Cartil"},{"issue":"11","key":"2750_CR3","first-page":"709","volume":"112","author":"MD Van Manen","year":"2012","unstructured":"Van Manen MD, Nace J, Mont MA. Management of primary knee osteoarthritis and indications for total knee arthroplasty for general practitioners. J Am Osteopath Assoc. 2012;112(11):709\u201315.","journal-title":"J Am Osteopath Assoc"},{"issue":"10158","key":"2750_CR4","doi-asserted-by":"publisher","first-page":"1672","DOI":"10.1016\/S0140-6736(18)32344-4","volume":"392","author":"AJ Price","year":"2018","unstructured":"Price AJ, Alvand A, Troelsen A, Katz JN, Hooper G, Gray A, et al. Knee replacement. Lancet. 2018;392(10158):1672\u201382 Available from: https:\/\/doi.org\/10.1016\/S0140-6736(18)32344-4.","journal-title":"Lancet."},{"issue":"1","key":"2750_CR5","doi-asserted-by":"publisher","first-page":"234","DOI":"10.1177\/0363546517697682","volume":"46","author":"JA McIntyre","year":"2018","unstructured":"McIntyre JA, Jones IA, Danilkovich A, Vangsness CT. The placenta: applications in orthopaedic sports medicine. Am J Sports Med. 2018;46(1):234\u201347.","journal-title":"Am J Sports Med"},{"key":"2750_CR6","doi-asserted-by":"crossref","unstructured":"Farr J, Gomoll AH, Yanke AB, Strauss EJ, Mowry KC. A randomized controlled single-blind study demonstrating superiority of amniotic suspension allograft injection over hyaluronic acid and saline control for modification of knee osteoarthritis symptoms.\u00a0J Knee Surg. 2019;32(11):1143\u201354. Available from: http:\/\/www.thieme-connect.de\/DOI\/DOI?10.1055\/s-0039-1696672.","DOI":"10.1055\/s-0039-1696672"},{"issue":"7","key":"2750_CR7","first-page":"E421","volume":"45","author":"N Heckmann","year":"2016","unstructured":"Heckmann N, Auran R, Mirzayan R. Application of amniotic tissue in orthopedic surgery. Am J Orthop (Belle Mead NJ). 2016;45(7):E421\u20135 Available from: http:\/\/www.ncbi.nlm.nih.gov\/pubmed\/28005118.","journal-title":"Am J Orthop (Belle Mead NJ)"},{"issue":"5","key":"2750_CR8","doi-asserted-by":"publisher","first-page":"1141","DOI":"10.1002\/jor.24559","volume":"38","author":"KA Kimmerling","year":"2020","unstructured":"Kimmerling KA, Gomoll AH, Farr J, Mowry KC. Amniotic suspension allograft modulates inflammation in a rat pain model of osteoarthritis. J Orthop Res. 2020;38(5):1141\u20139 Available from: https:\/\/doi.org\/10.1002\/jor.24559.","journal-title":"J Orthop Res"},{"issue":"1\u20132","key":"2750_CR9","doi-asserted-by":"publisher","first-page":"12","DOI":"10.1089\/ten.tea.2016.0088","volume":"23","author":"AL Raines","year":"2017","unstructured":"Raines AL, Shih MS, Chua L, Su CW, Tseng SCG, O\u2019Connell J. Efficacy of particulate amniotic membrane and umbilical cord tissues in attenuating cartilage destruction in an osteoarthritis model. Tissue Eng Part A. 2017;23(1\u20132):12\u20139.","journal-title":"Tissue Eng Part A"},{"issue":"9","key":"2750_CR10","doi-asserted-by":"publisher","first-page":"2425","DOI":"10.1177\/0363546515612750","volume":"44","author":"JC Riboh","year":"2016","unstructured":"Riboh JC, Saltzman BM, Yanke AB, Cole BJ. Human amniotic membrane-derived products in sports medicine: basic science, early results, and potential clinical applications. Am J Sports Med. 2016;44(9):2425\u201334.","journal-title":"Am J Sports Med"},{"issue":"6","key":"2750_CR11","doi-asserted-by":"publisher","first-page":"443","DOI":"10.1055\/s-0035-1569481","volume":"29","author":"JB Vines","year":"2016","unstructured":"Vines JB, Aliprantis AO, Gomoll AH, Farr J. Cryopreserved amniotic suspension for the treatment of knee osteoarthritis. J Knee Surg. 2016;29(6):443\u201350.","journal-title":"J Knee Surg"},{"issue":"1","key":"2750_CR12","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1186\/ar4476","volume":"16","author":"NJ Willett","year":"2014","unstructured":"Willett NJ, Thote T, Lin ASP, Moran S, Raji Y, Sridaran S, et al. Intra-articular injection of micronized dehydrated human amnion\/chorion membrane attenuates osteoarthritis development. Arthritis Res Ther. 2014;16(1):1\u201310 Available from: Arthritis Research & Therapy.","journal-title":"Arthritis Res Ther"},{"issue":"6","key":"2750_CR13","first-page":"E38","volume":"29","author":"JP McQuilling","year":"2017","unstructured":"McQuilling JP, Vines JB, Kimmerling KA, Mowry KC. Proteomic comparison of amnion and chorion and evaluation of the effects of processing on placental membranes. Wounds a Compend Clin Res Pract. 2017;29(6):E38\u201342.","journal-title":"Wounds a Compend Clin Res Pract"},{"issue":"4","key":"2750_CR14","first-page":"363","volume":"1","author":"AM Bendele","year":"2001","unstructured":"Bendele AM. Animal models of osteoarthritis. J Musculoskelet Neuronal Interact. 2001;1(4):363\u201376 Available from: http:\/\/www.ncbi.nlm.nih.gov\/pubmed\/15758487.","journal-title":"J Musculoskelet Neuronal Interact"},{"key":"2750_CR15","doi-asserted-by":"publisher","first-page":"149","DOI":"10.1007\/978-1-84628-701-5_9","volume-title":"Bone and osteoarthritis","author":"AM Bendele","year":"2007","unstructured":"Bendele AM. Animal models. In: Bronner F, Farach-Carson MC, editors. Bone and osteoarthritis; 2007. p. 149\u201364."},{"issue":"10","key":"2750_CR16","doi-asserted-by":"publisher","first-page":"785","DOI":"10.1053\/joca.2002.0823","volume":"10","author":"MJ Janusz","year":"2002","unstructured":"Janusz MJ, Bendele AM, Brown KK, Taiwo YO, Hsieh L, Heitmeyer SA. Induction of osteoarthritis in the rat by surgical tear of the meniscus: inhibition of joint damage by a matrix metalloproteinase inhibitor. Osteoarthr Cartil. 2002;10(10):785\u201391.","journal-title":"Osteoarthr Cartil"},{"issue":"7","key":"2750_CR17","doi-asserted-by":"publisher","first-page":"623","DOI":"10.1016\/j.joca.2005.03.003","volume":"13","author":"EE Moore","year":"2005","unstructured":"Moore EE, Bendele AM, Thompson DL, Littau A, Waggie KS, Reardon B, et al. Fibroblast growth factor-18 stimulates chondrogenesis and cartilage repair in a rat model of injury-induced osteoarthritis. Osteoarthr Cartil. 2005;13(7):623\u201331.","journal-title":"Osteoarthr Cartil"},{"issue":"1","key":"2750_CR18","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1371\/journal.pone.0171075","volume":"12","author":"SS Karhula","year":"2017","unstructured":"Karhula SS, Finnil\u00e4 MA, Lammi MJ, Yl\u00e4rinne JH, Kauppinen S, Rieppo L, et al. Effects of articular cartilage constituents on phosphotungstic acid enhanced micro-computed tomography. PLoS One. 2017;12(1):1\u201312.","journal-title":"PLoS One"},{"issue":"SUPPL. 3","key":"2750_CR19","doi-asserted-by":"publisher","first-page":"S24","DOI":"10.1016\/j.joca.2010.05.030","volume":"18","author":"N Gerwin","year":"2010","unstructured":"Gerwin N, Bendele AM, Glasson S, Carlson CS. The OARSI histopathology initiative - recommendations for histological assessments of osteoarthritis in the rat. Osteoarthr Cartil. 2010;18(SUPPL. 3):S24\u201334 Available from: https:\/\/doi.org\/10.1016\/j.joca.2010.05.030.","journal-title":"Osteoarthr Cartil"},{"key":"2750_CR20","doi-asserted-by":"crossref","unstructured":"TenBroek EM, Yunker L, Nies MF, Bendele AM. Randomized controlled studies on the efficacy of antiarthritic agents in inhibiting cartilage degeneration and pain associated with progression of osteoarthritis in the rat.\u00a0Arthritis Res Ther. 2016;18:24.","DOI":"10.1186\/s13075-016-0921-5"},{"issue":"1","key":"2750_CR21","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1038\/s41598-020-72350-7","volume":"10","author":"G A\u00fcllo-Rasser","year":"2020","unstructured":"A\u00fcllo-Rasser G, Dousset E, Roffino S, Zahouani H, Lecurieux-Clerville R, Argenson JN, et al. Early-stage knee OA induced by MIA and MMT compared in the murine model via histological and topographical approaches. Sci Rep. 2020;10(1):1\u201310 Available from: https:\/\/doi.org\/10.1038\/s41598-020-72350-7.","journal-title":"Sci Rep"},{"issue":"0","key":"2750_CR22","first-page":"1","volume":"0","author":"R Castellanos","year":"2019","unstructured":"Castellanos R, Tighe S. Injectable amniotic membrane\/umbilical cord particulate for knee osteoarthritis: a prospective, single-center pilot study. Pain Med. 2019;0(0):1\u20139.","journal-title":"Pain Med"},{"issue":"7","key":"2750_CR23","doi-asserted-by":"publisher","first-page":"2246","DOI":"10.1016\/j.arthro.2021.02.044","volume":"37","author":"AH Gomoll","year":"2021","unstructured":"Gomoll AH, Farr J, Cole BJ, Flanigan DC, Lattermann C, Mandelbaum BR, et al. Safety and efficacy of an amniotic suspension allograft injection over 12 months in a single-blinded, randomized controlled trial for symptomatic osteoarthritis of the knee. Arthrosc - J Arthrosc Relat Surg. 2021;37(7):2246\u201357 Available from: https:\/\/doi.org\/10.1016\/j.arthro.2021.02.044.","journal-title":"Arthrosc - J Arthrosc Relat Surg"},{"issue":"1","key":"2750_CR24","doi-asserted-by":"publisher","first-page":"295","DOI":"10.1136\/annrheumdis-2015-208913","volume":"76","author":"TP LaBranche","year":"2017","unstructured":"LaBranche TP, Bendele AM, Omura BC, Gropp KE, Hurst SI, Bagi CM, et al. Nerve growth factor inhibition with tanezumab influences weight-bearing and subsequent cartilage damage in the rat medial meniscal tear model. Ann Rheum Dis. 2017;76(1):295\u2013302.","journal-title":"Ann Rheum Dis"},{"issue":"1","key":"2750_CR25","first-page":"11","volume":"17","author":"IA Marino-Mart\u00ednez","year":"2019","unstructured":"Marino-Mart\u00ednez IA, Mart\u00ednez-Castro AG, Pe\u00f1a-Mart\u00ednez VM, Acosta-Olivo CA, V\u00edlchez-Cavazos F, Guzm\u00e1n-L\u00f3pez A, et al. Human amniotic membrane intra-articular injection prevents cartilage damage in an osteoarthritis model. Exp Ther Med. 2019;17(1):11\u20136.","journal-title":"Exp Ther Med"},{"issue":"2","key":"2750_CR26","first-page":"122","volume":"69","author":"J Thomas Vangsness","year":"2011","unstructured":"Thomas Vangsness J, Burke WS, Narvy SJ, MacPhee RD, Fedenko AN. Human knee synovial fluid cytokines correlated with grade of knee osteoarthritis: a pilot study. Bull NYU Hosp Jt Dis. 2011;69(2):122\u20137.","journal-title":"Bull NYU Hosp Jt Dis"},{"issue":"7","key":"2750_CR27","doi-asserted-by":"publisher","first-page":"533","DOI":"10.1038\/nri2356","volume":"8","author":"JA Hamilton","year":"2008","unstructured":"Hamilton JA. Colony-stimulating factors in inflammation and autoimmunity. Nat Rev Immunol. 2008;8(7):533\u201344.","journal-title":"Nat Rev Immunol"},{"issue":"4","key":"2750_CR28","doi-asserted-by":"publisher","first-page":"486","DOI":"10.1016\/j.joca.2020.01.012","volume":"28","author":"KMC Lee","year":"2020","unstructured":"Lee KMC, Prasad V, Achuthan A, Fleetwood AJ, Hamilton JA, Cook AD. Targeting GM-CSF for collagenase-induced osteoarthritis pain and disease in mice. Osteoarthr Cartil. 2020;28(4):486\u201391 Available from: https:\/\/doi.org\/10.1016\/j.joca.2020.01.012.","journal-title":"Osteoarthr Cartil"},{"issue":"3 PART 1","key":"2750_CR29","doi-asserted-by":"publisher","first-page":"900","DOI":"10.1016\/0002-9378(95)90363-1","volume":"173","author":"MJ Kupferminc","year":"1995","unstructured":"Kupferminc MJ, Peaceman AM, Aderka D, Wallach D, Peyser MR, Lessing JB, et al. Soluble tumor necrosis factor receptors in maternal plasma and second-trimester amniotic fluid. Am J Obstet Gynecol. 1995;173(3 PART 1):900\u20135.","journal-title":"Am J Obstet Gynecol"},{"issue":"6","key":"2750_CR30","doi-asserted-by":"publisher","first-page":"839","DOI":"10.1016\/j.joca.2013.03.003","volume":"21","author":"TE Macrini","year":"2013","unstructured":"Macrini TE, Coan HB, Levine SM, Lerma T, Saks CD, Araujo DJ, et al. Reproductive status and sex show strong effects on knee OA in a baboon model. Osteoarthr Cartil. 2013;21(6):839\u201348 Available from: https:\/\/doi.org\/10.1016\/j.joca.2013.03.003.","journal-title":"Osteoarthr Cartil"},{"issue":"6","key":"2750_CR31","doi-asserted-by":"publisher","first-page":"695","DOI":"10.1016\/j.joca.2006.11.005","volume":"15","author":"HL Ma","year":"2007","unstructured":"Ma HL, Blanchet TJ, Peluso D, Hopkins B, Morris EA, Glasson SS. Osteoarthritis severity is sex dependent in a surgical mouse model. Osteoarthr Cartil. 2007;15(6):695\u2013700.","journal-title":"Osteoarthr Cartil"}],"container-title":["Arthritis Research &amp; Therapy"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1186\/s13075-022-02750-9.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/article\/10.1186\/s13075-022-02750-9\/fulltext.html","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1186\/s13075-022-02750-9.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,3,4]],"date-time":"2022-03-04T13:44:11Z","timestamp":1646401451000},"score":1,"resource":{"primary":{"URL":"https:\/\/arthritis-research.biomedcentral.com\/articles\/10.1186\/s13075-022-02750-9"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,3,4]]},"references-count":31,"journal-issue":{"issue":"1","published-print":{"date-parts":[[2022,12]]}},"alternative-id":["2750"],"URL":"https:\/\/doi.org\/10.1186\/s13075-022-02750-9","relation":{},"ISSN":["1478-6362"],"issn-type":[{"type":"electronic","value":"1478-6362"}],"subject":[],"published":{"date-parts":[[2022,3,4]]},"assertion":[{"value":"29 December 2020","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"18 February 2022","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"4 March 2022","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"All in-life animal procedures were approved by the Bolder BioPATH Institutional Animal Care and Use Committee (IACUC) (Protocol #BBP-008).","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethics approval and consent to participate"}},{"value":"Not applicable.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Consent for publication"}},{"value":"KAK and KCM are employees of Organogenesis. AHG and JF are paid consultants for Organogenesis. All author disclosures can be found at .","order":4,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"63"}}