A single step, centrifuge-free method to harvest bone marrow highly concentrated in mesenchymal stem cells: results of a pilot trial.
Bone marrow aspirate
Bone marrow harvesting
Knee osteoarthritis
Mesenchymal stem cells
Journal
International orthopaedics
ISSN: 1432-5195
Titre abrégé: Int Orthop
Pays: Germany
ID NLM: 7705431
Informations de publication
Date de publication:
02 2022
02 2022
Historique:
received:
03
09
2021
accepted:
08
10
2021
pubmed:
3
11
2021
medline:
11
3
2022
entrez:
2
11
2021
Statut:
ppublish
Résumé
The aims of the present study were: (1) to characterize the bone-marrow aspirate (BMA) obtained with a centrifuge-free process, employing a dedicated aspiration device; (2) to test the in vitro efficacy of BMA in a model of cartilage inflammation; and (3) to report the preliminary clinical results in a small cohort of patients affected by knee OA. Ten patients (4 M, 6 W; mean age: 51.9 ± 9.2 yy) affected by mild to moderate unicompartmental knee OA (KL grade 2-3) were treated by intra-articular and subchondral injections of BMA obtained by a centrifuge-free process. To evaluate the effectiveness of the device in harvesting mesenchymal stem cells (MSCs), samples of the obtained BMA were tested by flow cytometry before and after subculture; BMA ability to counteract inflammation was also tested in an in vitro model of cartilage cell inflammation, evaluating the expression of MMP1, MMP3, TGFβ and TIMP-1 by real-time PCR. Patients were also evaluated up to two years' follow-up by using: VAS for pain, IKDC-subjective and KOOS scores. The laboratory analysis showed that BMSCs accounted for 0.011% of BMA cells, similar to what had been expected in native bone marrow. The paracrine activity of BMA was able to reduce in vitro the catabolic response of human chondrocyte, as shown by the decrease in metalloproteases concentration and increase in anti-inflammatory mediators. Moreover, the clinical evaluation showed significant improvements in all scores adopted, with stable results up to two years. The present data showed the effectiveness of the study device to harvest pure bone marrow with minimal peripheral blood contamination. The relevant content of MSCs resulted in the ability to counteract the catabolic cascade through a paracrine action. The clinical outcomes in patients affected by unicompartmental knee OA were encouraging in terms of pain reduction and functional improvement up to mid-term evaluation.
Identifiants
pubmed: 34727209
doi: 10.1007/s00264-021-05243-7
pii: 10.1007/s00264-021-05243-7
doi:
Types de publication
Clinical Trial
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
391-400Commentaires et corrections
Type : ErratumIn
Informations de copyright
© 2021. The Author(s), under exclusive licence to The Author(s) under exclusive licence to SICOT aisbl.
Références
Cavallo C, Boffa A, Andriolo L et al (2021) Bone marrow concentrate injections for the treatment of osteoarthritis: evidence from preclinical findings to the clinical application. Int Orthop (SICOT) 45:525–538. https://doi.org/10.1007/s00264-020-04703-w
doi: 10.1007/s00264-020-04703-w
Imam MA, Holton J, Ernstbrunner L et al (2017) A systematic review of the clinical applications and complications of bone marrow aspirate concentrate in management of bone defects and nonunions. Int Orthop 41:2213–2220. https://doi.org/10.1007/s00264-017-3597-9
doi: 10.1007/s00264-017-3597-9
pubmed: 28804813
Palombella S, Lopa S, Gianola S et al (2019) Bone marrow-derived cell therapies to heal long-bone nonunions: a systematic review and meta-analysis—which is the best available treatment? Stem Cells Int 2019:e3715964. https://doi.org/10.1155/2019/3715964
doi: 10.1155/2019/3715964
Sampson S, Botto-van Bemden A, Aufiero D (2013) Autologous bone marrow concentrate: review and application of a novel intra-articular orthobiologic for cartilage disease. Phys Sportsmed 41:7–18. https://doi.org/10.3810/psm.2013.09.2022
doi: 10.3810/psm.2013.09.2022
pubmed: 24113698
Murphy MB, Moncivais K, Caplan AI (2013) Mesenchymal stem cells: environmentally responsive therapeutics for regenerative medicine. Exp Mol Med 45:e54. https://doi.org/10.1038/emm.2013.94
doi: 10.1038/emm.2013.94
pubmed: 24232253
pmcid: 3849579
Colombini A, Perucca Orfei C, Kouroupis D et al (2019) Mesenchymal stem cells in the treatment of articular cartilage degeneration: new biological insights for an old-timer cell. Cytotherapy 21:1179–1197. https://doi.org/10.1016/j.jcyt.2019.10.004
doi: 10.1016/j.jcyt.2019.10.004
pubmed: 31784241
Murphy EP, Fenelon C, McGoldrick NP, Kearns SR (2018) Bone marrow aspirate concentrate and microfracture technique for talar osteochondral lesions of the ankle. Arthrosc Tech 7:e391. https://doi.org/10.1016/j.eats.2017.10.011
doi: 10.1016/j.eats.2017.10.011
pubmed: 29868410
pmcid: 5982938
Kreuz PC, Steinwachs MR, Erggelet C et al (2006) Results after microfracture of full-thickness chondral defects in different compartments in the knee. Osteoarthritis Cartilage 14:1119–1125. https://doi.org/10.1016/j.joca.2006.05.003
doi: 10.1016/j.joca.2006.05.003
pubmed: 16815714
Wong KL, Lee KBL, Tai BC et al (2013) 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 29:2020–2028. https://doi.org/10.1016/j.arthro.2013.09.074
doi: 10.1016/j.arthro.2013.09.074
pubmed: 24286801
Shin Y-S, Yoon J-R, Kim H-S, Lee S-H (2018) Intra-articular injection of bone marrow-derived mesenchymal stem cells leading to better clinical outcomes without difference in MRI outcomes from baseline in patients with knee osteoarthritis. Knee Surg Relat Res 30:206–214. https://doi.org/10.5792/ksrr.17.201
doi: 10.5792/ksrr.17.201
pubmed: 29983008
pmcid: 6122947
Ganguly P, El-Jawhari JJ, Giannoudis PV et al (2017) Age-related changes in bone marrow mesenchymal stromal cells: a potential impact on osteoporosis and osteoarthritis development. Cell Transplant 26(9):1520–1529. https://doi.org/10.1177/0963689717721201
doi: 10.1177/0963689717721201
pubmed: 29113463
pmcid: 5680949
Schäfer R, DeBaun MR, Fleck E et al (2019) Quantitation of progenitor cell populations and growth factors after bone marrow aspirate concentration. J Transl Med 17:115. https://doi.org/10.1186/s12967-019-1866-7
doi: 10.1186/s12967-019-1866-7
pubmed: 30961655
pmcid: 6454687
Narbona-Carceles J, Vaquero J, Suárez-Sancho SBS et al (2014) Bone marrow mesenchymal stem cell aspirates from alternative sources: is the knee as good as the iliac crest? Injury 45(Suppl 4):S42-47. https://doi.org/10.1016/S0020-1383(14)70009-9
doi: 10.1016/S0020-1383(14)70009-9
pubmed: 25384474
Hernigou P, Homma Y, Flouzat Lachaniette CH et al (2013) Benefits of small volume and small syringe for bone marrow aspirations of mesenchymal stem cells. Int Orthop 37:2279–2287. https://doi.org/10.1007/s00264-013-2017-z
doi: 10.1007/s00264-013-2017-z
pubmed: 23881064
pmcid: 3824897
Chong P-P, Selvaratnam L, Abbas AA, Kamarul T (2012) Human peripheral blood derived mesenchymal stem cells demonstrate similar characteristics and chondrogenic differentiation potential to bone marrow derived mesenchymal stem cells. J Orthop Res 30:634–642. https://doi.org/10.1002/jor.21556
doi: 10.1002/jor.21556
pubmed: 21922534
Friedenstein AJ, Latzinik NW, Grosheva AG, Gorskaya UF (1982) Marrow microenvironment transfer by heterotopic transplantation of freshly isolated and cultured cells in porous sponges. Exp Hematol 10:217–227
pubmed: 6120850
Wexler SA, Donaldson C, Denning-Kendall P et al (2003) Adult bone marrow is a rich source of human mesenchymal “stem” cells but umbilical cord and mobilized adult blood are not. Br J Haematol 121:368–374. https://doi.org/10.1046/j.1365-2141.2003.04284.x
doi: 10.1046/j.1365-2141.2003.04284.x
pubmed: 12694261
Krause DS, Fackler MJ, Civin CI, May WS (1996) CD34: structure, biology, and clinical utility. Blood 87:1–13
doi: 10.1182/blood.V87.1.1.1
pubmed: 8547630
Varady NH, Cate G, Barghi A et al (2020) Positive early clinical outcomes of bone marrow aspirate concentrate for osteoarthritis using a novel fenestrated trocar. Knee 27:1627–1634. https://doi.org/10.1016/j.knee.2020.08.018
doi: 10.1016/j.knee.2020.08.018
pubmed: 33010782
Lv F-J, Tuan RS, Cheung KMC, Leung VYL (2014) Concise review: the surface markers and identity of human mesenchymal stem cells. Stem Cells 32:1408–1419. https://doi.org/10.1002/stem.1681
doi: 10.1002/stem.1681
pubmed: 24578244
Han Y, Li X, Zhang Y et al (2019) Mesenchymal stem cells for regenerative medicine. Cells 8(8):886. https://doi.org/10.3390/cells8080886
doi: 10.3390/cells8080886
pmcid: 6721852
Scarpone M, Kuebler D, Chambers A et al (2019) Isolation of clinically relevant concentrations of bone marrow mesenchymal stem cells without centrifugation. J Transl Med 17:10. https://doi.org/10.1186/s12967-018-1750-x
doi: 10.1186/s12967-018-1750-x
pubmed: 30611285
pmcid: 6321705
Hegde V, Shonuga O, Ellis S et al (2014) A prospective comparison of 3 approved systems for autologous bone marrow concentration demonstrated nonequivalency in progenitor cell number and concentration. J Orthop Trauma 28:591–598. https://doi.org/10.1097/BOT.0000000000000113
doi: 10.1097/BOT.0000000000000113
pubmed: 24694554
McLain RF, Fleming JE, Boehm CA, Muschler GF (2005) Aspiration of osteoprogenitor cells for augmenting spinal fusion: comparison of progenitor cell concentrations from the vertebral body and iliac crest. J Bone Joint Surg Am 87:2655–2661. https://doi.org/10.2106/JBJS.E.00230
doi: 10.2106/JBJS.E.00230
pubmed: 16322615
De Luca P, Kouroupis D, Viganò M et al (2019) Human diseased articular cartilage contains a mesenchymal stem cell-like population of chondroprogenitors with strong immunomodulatory responses. J Clin Med 8:423. https://doi.org/10.3390/jcm8040423
doi: 10.3390/jcm8040423
pmcid: 6517884
Wang M, Zhou Y, Huang W et al (2020) Association between matrix metalloproteinase-1 (MMP-1) protein level and the risk of rheumatoid arthritis and osteoarthritis: a meta-analysis. Braz J Med Biol Res 54:e10366. https://doi.org/10.1590/1414-431X202010366
doi: 10.1590/1414-431X202010366
pubmed: 33331536
pmcid: 7727110
Zhou L, Ye H, Liu L, Chen Y (2021) Human Bone mesenchymal stem cell-derived exosomes inhibit IL-1β-induced inflammation in osteoarthritis chondrocytes. Cell J 23:485–494. https://doi.org/10.22074/cellj.2021.7127
doi: 10.22074/cellj.2021.7127
pubmed: 34455725
pmcid: 8405079
Gato-Calvo L, Hermida-Gómez T, Romero CR et al (2019) Anti-inflammatory effects of novel standardized platelet rich plasma releasates on knee osteoarthritic chondrocytes and cartilage in vitro. Curr Pharm Biotechnol 20:920–933. https://doi.org/10.2174/1389201020666190619111118
doi: 10.2174/1389201020666190619111118
pubmed: 31237204
Yang J, Guo A, Li Q, Wu J (2021) Platelet-rich plasma attenuates interleukin-1β-induced apoptosis and inflammation in chondrocytes through targeting hypoxia-inducible factor-2α. Tissue Cell 73:101646. https://doi.org/10.1016/j.tice.2021.101646
doi: 10.1016/j.tice.2021.101646
pubmed: 34536814
Dabrowski MP, Stankiewicz W, Płusa T et al (2001) Competition of IL-1 and IL-1ra determines lymphocyte response to delayed stimulation with PHA. Mediators Inflamm 10:101–107
doi: 10.1080/09629350124376
pubmed: 11545246
pmcid: 1781706
Ortiz LA, DuTreil M, Fattman C et al (2007) Interleukin 1 receptor antagonist mediates the antiinflammatory and antifibrotic effect of mesenchymal stem cells during lung injury. Proc Natl Acad Sci U S A 104:11002–11007. https://doi.org/10.1073/pnas.0704421104
doi: 10.1073/pnas.0704421104
pubmed: 17569781
pmcid: 1891813
Caplan AI, Correa D (2011) The MSC: an injury drugstore. Cell Stem Cell 9:11–15. https://doi.org/10.1016/j.stem.2011.06.008
doi: 10.1016/j.stem.2011.06.008
pubmed: 21726829
pmcid: 3144500
Matteo BD, Filardo G, Kon E, Marcacci M (2015) Platelet-rich plasma: evidence for the treatment of patellar and Achilles tendinopathy—a systematic review. Musculoskelet Surg 99(1):1–9. https://doi.org/10.1007/s12306-014-0340-1
doi: 10.1007/s12306-014-0340-1
pubmed: 25323041
Liu Z, Simpson RJ, Cheers C (1995) Interaction of interleukin-6, tumour necrosis factor and interleukin-1 during Listeria infection. Immunology 85:562–567
pubmed: 7558150
pmcid: 1383784
Khella CM, Asgarian R, Horvath JM et al (2021) An evidence-based systematic review of human knee Post-Traumatic Osteoarthritis (PTOA): timeline of clinical presentation and disease markers, comparison of knee joint PTOA models and early disease implications. Int J Mol Sci 22(4):1996. https://doi.org/10.3390/ijms22041996
doi: 10.3390/ijms22041996
pubmed: 33671471
pmcid: 7922905
Wiegertjes R, Thielen NGM, van Caam APM et al (2021) Increased IL-6 receptor expression and signaling in ageing cartilage can be explained by loss of TGF-β-mediated IL-6 receptor suppression. Osteoarthr Cartil. https://doi.org/10.1016/j.joca.2021.01.008
doi: 10.1016/j.joca.2021.01.008
pubmed: 33617971
Viganò M, Lugano G, Perucca Orfei C et al (2019) Autologous microfragmented adipose tissue reduces the catabolic and fibrosis response in an in vitro model of tendon cell inflammation. Stem Cells Int 2019:5620286. https://doi.org/10.1155/2019/5620286
doi: 10.1155/2019/5620286
pubmed: 31885616
pmcid: 6915130
Chahla J, Dean CS, Moatshe G et al (2016) Concentrated bone marrow aspirate for the treatment of chondral injuries and osteoarthritis of the knee: a systematic review of outcomes. Orthop J Sports Med 4:2325967115625481. https://doi.org/10.1177/2325967115625481
doi: 10.1177/2325967115625481
pubmed: 26798765
pmcid: 4714134
Colberg RE, Jurado Vélez JA, Walsh KP, Fleisig G (2020) Short-term outcomes after pure bone marrow aspirate injection for severe knee osteoarthritis: a case series. Regen Med 15:1851–1859. https://doi.org/10.2217/rme-2019-0113
doi: 10.2217/rme-2019-0113
pubmed: 32885730