Hip osteoarthritis (HOA) is a prevalent degenerative joint disease with various treatment approaches. Biological agents, such as bone-marrow derived stem cells (BM-MSC) therapy, have recently been proposed as a treatment option in the management of HOA.
Purpose:
We sought to further analyze the use of BM-MSC therapy by investigating the following questions. What is the standard preparation and practice? Does a dose response exist between stem cell therapy and clinical outcome? Does BM-MSC therapy alone produce effective clinical outcomes?
Methods:
We conducted a scoping review using the Methodological Expectations of Cochrane Intervention Reviews Manual and the Preferred Reporting Items for Systematic Review and Meta-Analysis (PRISMA) guidelines for scoping reviews. A comprehensive search of PubMed, Embase, Cochrane CENTRAL, Scopus, SPORTDiscus, Cumulative Index to Nursing and Allied Health Literature, and Web of Science Core Collection was performed in June 2023 of studies using exclusively BM-MSC injections for the treatment of HOA. Study characteristic, injection preparation and dosage, clinical outcome measures, and adverse effect data were extracted and interpreted by 3 reviewers.
Results:
Seven studies with a total of 72 patients met the inclusion criteria. Clinical outcome following intra-articular injection of BM-MSCs was measured using the numerical pain scale, the Western Ontario and McMaster Universities Osteoarthritis Index, the visual analogue scale, and other scores, all of which showed reduction in pain and increase in functional ability across studies.
Conclusions:
This scoping review found that the efficacy of BM-MSC therapy alone in the treatment of HOA appeared beneficial, improving clinical outcomes in each study. All 7 studies used “low-dose” injections with variable follow-up times; thus, a clear dose–response relationship cannot be drawn. Future studies using high doses and analyzing long-term effects of BM-MSC injections in HOA are needed.
AlghadirAHAnwerSIqbalAIqbalZA.Test-retest reliability, validity, and minimum detectable change of visual analog, numerical rating, and verbal rating scales for measurement of osteoarthritic knee pain. J Pain Res. 2018;11:851–856. https://doi.org/10.2147/JPR.S158847.
2.
AlvesCHFarrellEVisMColinEMLubbertsE.Animal models of bone loss in inflammatory arthritis: from cytokines in the bench to novel treatments for bone loss in the bedside—a comprehensive review. Clin Rev Allerg Immunol. 2016;51(1):27–47. https://doi.org/10.1007/s12016-015-8522-7.
3.
ArrigoniCD’arrigoDRossellaVCandrianCAlbertiniVMorettiM.Umbilical cord MSCs and their secretome in the therapy of arthritic diseases: a research and industrial perspective. Cells. 2020;9(6):1343. https://doi.org/10.3390/cells9061343.
4.
BertoniLBranlyTJacquetS, et al. Intra-articular injection of 2 different dosages of autologous and allogeneic bone marrow- and umbilical cord-derived mesenchymal stem cells triggers a variable inflammatory response of the fetlock joint on 12 sound experimental horses. Stem Cells Int. 2019;2019:9431894. https://doi.org/10.1155/2019/9431894.
5.
BurnhamRSmithAHartD.The safety and effectiveness of bone marrow concentrate injection for knee and hip osteoarthritis: a Canadian cohort. Regen Med. 2021;16(7):619–628. https://doi.org/10.2217/rme-2021-0001.
CentenoCJAl-SayeghHBashirJGoodyearSFreemanMD.A dose response analysis of a specific bone marrow concentrate treatment protocol for knee osteoarthritis. BMC Musculoskelet Disord. 2015;16:258. https://doi.org/10.1186/s12891-015-0714-z.
8.
CentenoCJAl-SayeghHFreemanMDSmithJMurrellWDBubnovR.A multi-center analysis of adverse events among two thousand, three hundred and seventy two adult patients undergoing adult autologous stem cell therapy for orthopaedic conditions. Int Orthop. 2016;40(8):1755–1765. https://doi.org/10.1007/s00264-016-3162-y.
9.
CentenoCJKisidayJFreemanMSchultzJR.Partial regeneration of the human hip via autologous bone marrow nucleated cell transfer: a case study. Pain Physician. 2006;9(3):253–256.
ChaofanZXinyuFZidaH, et al. Addition of bone marrow stem cells therapy achieves better clinical outcomes and lower rates of disease progression compared with core decompression alone for early stage osteonecrosis of the femoral head: a systematic review and meta-analysis. J Am Acad Orthopaedic Surg. 2020;28(23):973–979. https://doi.org/10.5435/JAAOS-D-19-00816.
12.
ChavdaSRabbaniSAWadhwaT.Role and effectiveness of intra-articular injection of hyaluronic acid in the treatment of knee osteoarthritis: a systematic review. Cureus. 2022;14(4):e24503. https://doi.org/10.7759/cureus.24503.
13.
ChoueiriMChevalierXEymardF.Intraarticular corticosteroids for hip osteoarthritis: a review. Cartilage. 2021;13(1 suppl.):122S–131S. https://doi.org/10.1177/1947603520951634.
14.
ColbergREJurado VelezJAWalshKPFleisigG.Short-term outcomes after pure bone marrow aspirate injection for severe knee osteoarthritis: a case series. Regen Med. 2020;15(7):1851–1859. https://doi.org/10.2217/rme-2019-0113.
15.
DaltroGFrancoBAFaleiroTB, et al. Use of autologous bone marrow stem cell implantation for osteonecrosis of the knee in sickle cell disease: a preliminary report. BMC Musculoskelet Disorder. 2018;19:158. https://doi.org/10.1186/s12891-018-2067-x.
16.
DarrowMShawBDarrowBWiszS.Short-term outcomes of treatment of hip osteoarthritis with 4 bone marrow concentrate injections: a case series. Clin Med Insight. 2018;11:1179547618791574.https://doi.org/10.1177/1179547618791574.
17.
Del RealALópez-DelgadoLSañudoC, et al. Long noncoding RNAs as bone marrow stem cell regulators in osteoporosis. DNA Cell Biol. 2020;39(9):1691–1699. https://doi.org/10.1089/dna.2020.5672.
EmadedinMGhorbani LiastaniMFazeliR, et al. Long-term follow-up of intra-articular injection of autologous mesenchymal stem cells in patients with knee, ankle, or hip osteoarthritis. Arch Iran Med. 2015;18(6):336–344.
20.
FanZYanLLiuH, et al. The prevalence of hip osteoarthritis: a systematic review and meta-analysis. Arthrit Res Ther. 2023;25(1):51. https://doi.org/10.1186/s13075-023-03033-7.
21.
FennemaEMRenardAJLeusinkAvan BlitterswijkCAde BoerJ.The effect of bone marrow aspiration strategy on the yield and quality of human mesenchymal stem cells. Acta Orthop. 2009;80(5):618–621. https://doi.org/10.3109/17453670903278241.
22.
GadelkarimMAbd ElmegeedAAllamAH, et al. Safety and efficacy of adipose-derived mesenchymal stem cells for knee osteoarthritis: a systematic review and m-analysis. Joint Bone Spine. 2022;89(5):105404. https://doi.org/10.1016/j.jbspin.2022.105404.
23.
GuptaPKThejC.Mesenchymal stromal cells for the treatment of osteoarthritis of knee joint: context and perspective. Ann Transl Med. 2019;7(suppl. 6):S179. https://doi.org/10.21037/atm.2019.07.54.
24.
HaoCWangYShaoLLiuJChenLZhaoZ.Local injection of bone mesenchymal stem cells and fibrin glue promotes the repair of bone atrophic nonunion in vivo. Adv Therapy. 2016;33(5):824–833. https://doi.org/10.1007/s12325-016-0329-2.
25.
Harrison-BrownMScholesCHafsiK, et al. Efficacy and safety of culture-expanded, mesenchymal stem/stromal cells for the treatment of knee osteoarthritis: a systematic review protocol. J Orthop Surg Res. 2019;14(1):34. https://doi.org/10.1186/s13018-019-1070-8.
26.
HauserRAOrlofskyA.Regenerative injection therapy with whole bone marrow aspirate for degenerative joint disease: a case series. Clin Med Insight. 2013;6:S10951. https://doi.org/10.4137/CMAMD.S10951.
27.
HerrmannMDiederichsSMelnikS, et al. Extracellular vesicles in musculoskeletal pathologies and regeneration. Front Bioeng Biotechnol. 2020;8:624096. https://doi.org/10.3389/fbioe.2020.624096.
ImGIShinYWLeeKB.Do adipose tissue-derived mesenchymal stem cells have the same osteogenic and chondrogenic potential as bone marrow-derived cells?Osteoarthr Cartilage. 2005;13(10):845–853. https://doi.org/10.1016/j.joca.2005.05.005.
30.
Lamo-EspinosaJMMoraGBlancoJF, et al. Intra-articular injection of two different doses of autologous bone marrow mesenchymal stem cells versus hyaluronic acid in the treatment of knee osteoarthritis: multicenter randomized controlled clinical trial (phase I/II). J Transl Med. 2016;14(1):246. https://doi.org/10.1186/s12967-016-0998-2.
31.
LeeEEpanomeritakisIELuVKhanW.Bone marrow-derived mesenchymal stem cell implants for the treatment of focal chondral defects of the knee in animal models: a systematic review and meta-analysis. Int J Molec Sci. 2023;24(4):3227. https://doi.org/10.3390/ijms24043227.
32.
LockwoodCMunnZPorrittK.Qualitative research synthesis: methodological guidance for systematic reviewers utilizing meta-aggregation. Int J Evid Based Healthc. 2015;13(3):179–187. https://doi.org/10.1097/XEB.0000000000000062.
33.
MardonesRJofreCMTobarLMinguellJJ.Mesenchymal stem cell therapy in the treatment of hip osteoarthritis. J Hip Preserv Surg. 2017;4(2):159–163. https://doi.org/10.1093/jhps/hnx011.
34.
McAlindonTEBannuruRRSullivanMC, et al. OARSI guidelines for the non-surgical management of knee osteoarthritis. Osteoarthritis Cartilage. 2014;22(3):363–388. https://doi.org/10.1016/j.joca.2014.01.003.
35.
Mohamed-AhmedSFristadILieSA, et al. Adipose-derived and bone marrow mesenchymal stem cells: a donor-matched comparison. Stem Cell Res Ther. 2018;9(1):168. https://doi.org/10.1186/s13287-018-0914-1.
36.
MunnZBarkerTHMoolaS, et al. Methodological quality of case series studies: an introduction to the JBI critical appraisal tool. JBI Evid Synth. 2020;18(10):2127–2133. https://doi.org/10.11124/JBISRIR-D-19-00099.
RampalSJaimanATokgözMA, et al. A review of the efficacy of intraarticular hip injection for patients with hip osteoarthritis: to inject or not to inject in hip osteoarthritis?Joint Dis Relat Surg. 2022;33(1):255–262. https://doi.org/10.52312/jdrs.2022.402.
39.
Rodriguez-FontanFPiuzziNSKraeutlerMJPascual-GarridoC.Early clinical outcomes of intra-articular injections of bone marrow aspirate concentrate for the treatment of early osteoarthritis of the hip and knee: a cohort study. PM and R. 2018;10(12):1353–1359. https://doi.org/10.1016/j.pmrj.2018.05.016.
40.
Rodriguez-MerchanEC.Intraarticular injections of mesenchymal stem cells in knee osteoarthritis: a review of their current molecular mechanisms of action and their efficacy. Int J Mol Sci. 2022;23(23):14953. https://doi.org/10.3390/ijms232314953.
41.
SatinAMNorelliJPlazaDLiangHSgaglioneNAGrandeD.Effect of combined platelet-rich plasma and hyaluronic acid on BMSC and chondrocyte metabolism [Conference Abstract]. J Orthopaedic Res. 2017;3:5.
42.
TheisKAMurphyLBGuglielmoD, et al. Prevalence of arthritis and arthritis—attributable activity limitation—United States, 2016-2018. MMWR Morb Mortal Wkly Rep. 2021;70(40):1401–1407. https://doi.org/10.15585/mmwr.mm7040a2.
43.
TriccoACLillieEZarinW, et al. PRISMA Extension for Scoping Reviews (PRISMA-ScR): checklist and explanation. Ann Intern Med. 2018;169(7):467–473. https://doi.org/10.7326/M18-0850.
44.
TsujiWRubinJPMarraKG.Adipose-derived stem cells: implications in tissue regeneration. World J Stem Cells. 2014;6(3):312–321. https://doi.org/10.4252/wjsc.v6.i3.312.
45.
VangsnessCTJrFarrJIIBoydJ, et al. Adult human mesenchymal stem cells delivered via intra-articular injection to the knee following partial medial meniscectomy: a randomized, double-blind, controlled study. J Bone Joint Surg Am. 2014;96(2):90–98. https://doi.org/10.2106/JBJS.M.00058.
46.
WakitaniSImotoKYamamotoTSaitoMMurataNYonedaM.Human autologous culture expanded bone marrow mesenchymal cell transplantation for repair of cartilage defects in osteoarthritic knees. Osteoarthritis Cartilage. 2002;10(3):199–206. https://doi.org/10.1053/joca.2001.0504.
47.
WaluyoYArtikaSRInsani NandaWGunawanAZainalATF. Efficacy of prolotherapy for osteoarthritis: a systematic review. J Rehabil Med. 2023;55:jrm00372. https://doi.org/10.2340/jrm.v55.2572.
48.
WhitneyKEBriggsKKChamnessC, et al. Bone marrow concentrate injection treatment improves short-term outcomes in symptomatic hip osteoarthritis patients: a pilot study. Orthopaedic J Sport Med. 2020;8(12):2325967120966162. https://doi.org/10.1177/2325967120966162.
49.
WongKLLeeKBTaiBCLawPLeeEHHuiJH.Injectable cultured bone marrow-derived mesenchymal stem cells in varus knees with cartilage defects undergoing high tibial osteotomy: a prospective, randomized controlled clinical trial with 2 years’ follow-up. Arthroscopy. 2013;29(12):2020–2028. https://doi.org/10.1016/j.arthro.2013.09.074.
50.
WuBLiYMLiuYC.Efficacy of intra-articular hyaluronic acid injections in hip osteoarthritis: a meta-analysis of randomized controlled trials. Oncotarget. 2017;8(49):86865–86876. https://doi.org/10.18632/oncotarget.20995.
51.
YuYLuQLiS, et al. Intra-articular injection of autologous micro-fragmented adipose tissue for the treatment of knee osteoarthritis: a prospective interventional study. J Person Med. 2023;13(3):504. https://doi.org/10.3390/jpm13030504.
52.
ZaffagniniSAndrioloLBoffaA, et al. Microfragmented adipose tissue versus platelet-rich plasma for the treatment of knee osteoarthritis: a prospective randomized controlled trial at 2-year follow-up. Am J Sport Med. 2022;50(11):2881–2892. https://doi.org/10.1177/03635465221115821.
53.
ZampognaBPapaliaRPapaliaGF, et al. The role of physical activity as conservative treatment for hip and knee osteoarthritis in older people: a systematic review and meta-analysis. J Clin Med. 2020;9(4):1167. https://doi.org/10.3390/jcm9041167.
54.
ZhangYBiQLuoJTongYYuTZhangQ.The effect of autologous adipose-derived stromal vascular fractions on cartilage regeneration was quantitatively evaluated based on the 3D-FS-SPGR sequence: a clinical trial study [published online ahead of print January 25, 2022]. Biomed Res Int. https://doi.org/10.1155/2022/2777568.
55.
ZhuCWuWQuX.Mesenchymal stem cells in osteoarthritis therapy: a review. Am J Transl Res. 2021;13(2):448–461.
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