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Combination of Filtered Bone Marrow Aspirate and Biomimetic Scaffold for the Treatment of Knee Osteochondral Lesions: Cellular and Early Clinical Results of a Single Centre Case Series

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Tissue Engineering and Regenerative Medicine Aims and scope

Abstract

Background:

Osteochondral injury is a very common orthopaedic pathology, mainly affecting young, active population, with limited current treatment options. Herein we are presenting cellular and early clinical data of a patient series treated for chronic osteochondral lesions in the knee with a filter-based intra-operative bone marrow aspirate (BMA) separation device.

Methods:

Fifteen patients with chronic knee osteochondral lesions (60% females, 19–59 years) were included in this prospective case series. Filtered BMA (f-BMA), containing mesenchymal stem/stromal cells (MSCs), was combined with a biomimetic collagen-hydroxyapatite scaffold (CHAS) and implanted into the site of the lesion. Harvested BMA and post-separation f-BMA were analysed for blood cell counts, flow cytometry, and fibroblast colony forming units (CFU-Fs). Patients were followed for serious adverse events and graft failures. Clinical evaluation was assessed using the knee injury and osteoarthritis outcome score (KOOS). In 8 patients a magnetic resonance imaging (MRI)/arthroscopy were performed.

Results:

Cell suspension contained 0.027% CD271+ CD45 7-AAD cells, 0.15% CD73+ CD90+ CD105+ cells and 0.0012% CFU-Fs of all nucleated cells with 86% viability. Filtration process resulted in 12.8 (4.0–40.8) fold enrichment in terms of CFU-F content in comparison to initial BMA. No serious adverse events related directly to the osteochondral treatment were reported. After an average follow-up of 20 months (14–25) all KOOS subscales (Symptoms/Pain/Daily activities/Sport and recreation/Quality of life) increased significantly from pre-operative 55/56/67/30/30 to post-operative 73/76/79/51/52 (p values < 0.05), respectively. MRI or arthroscopic evaluation revealed nearly normal to normal overall International Cartilage Repair Society assessment in 7/8 patients.

Conclusion:

The filter-based BMA separation procedure significantly increased the frequency of mesenchymal stem/stromal cells (MSCs), however their concentration was not increased. The clinical evaluation revealed high safety profile of the treatment and resulted in improved clinical status of the patients.

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References

  1. Hjelle K, Solheim E, Strand T, Muri R, Brittberg M. Articular cartilage defects in 1000 knee arthroscopies. Arthroscopy. 2002;18:730–4.

    Article  Google Scholar 

  2. Grässel S, Lorenz J. Tissue-engineering strategies to repair chondral and osteochondral tissue in osteoarthritis: use of mesenchymal stem cells. Curr Rheumatol Rep. 2014;16:452.

    Article  Google Scholar 

  3. Muschler GF, Midura RJ, Nakamoto C. Practical modeling concepts for connective tissue stem cell and progenitor compartment kinetics. J Biomed Biotechnol. 2003;2003:170–93.

    Article  Google Scholar 

  4. Richter W. Mesenchymal stem cells and cartilage in situ regeneration. J Intern Med. 2009;266:390–405.

    Article  CAS  Google Scholar 

  5. Brittberg M, Lindahl A, Nilsson A, Ohlsson C, Isaksson O, Peterson L. Treatment of deep cartilage defects in the knee with autologous chondrocyte transplantation. N Engl J Med. 1994;331:889–95.

    Article  CAS  Google Scholar 

  6. Martinčič D, Radosavljevič D, Drobnič M. Ten-year clinical and radiographic outcomes after autologous chondrocyte implantation of femoral condyles. Knee Surg Sports Traumatol Arthrosc. 2014;22:1277–83.

    Article  Google Scholar 

  7. Veronesi F, Giavaresi G, Tschon M, Borsari V, Nicoli Aldini N, Fini M. Clinical use of bone marrow, bone marrow concentrate, and expanded bone marrow mesenchymal stem cells in cartilage disease. Stem Cells Dev. 2013;22:181–92.

    Article  CAS  Google Scholar 

  8. Coelho MB, Cabral JMS, Karp JM. Intraopera stem cell therapy. Annu Rev Biomed Eng. 2012;14:325–49.

    Article  CAS  Google Scholar 

  9. Caplan AI, Correa D. The MSC: an injury drugstore. Cell Stem Cell. 2011;9:11–5.

    Article  CAS  Google Scholar 

  10. Hass R, Kasper C, Böhm S, Jacobs R. Different populations and sources of human mesenchymal stem cells (MSC): a comparison of adult and neonatal tissue-derived MSC. Cell Commun Signal. 2011;9:12.

    Article  CAS  Google Scholar 

  11. Kon E, Filardo G, Di Martino A, Busacca M, Moio A, Perdisa F, et al. Clinical results and MRI evolution of a nano-composite multilayered biomaterial for osteochondral regeneration at 5 years. Am J Sports Med. 2014;42:158–65.

    Article  Google Scholar 

  12. Kon E, Filardo G, Brittberg M, Busacca M, Condello V, Engebretsen L, et al. A multilayer biomaterial for osteochondral regeneration shows superiority vs microfractures for the treatment of osteochondral lesions in a multicentre randomized trial at 2 years. Knee Surg Sports Traumatol Arthrosc. 2018;26:2704–15.

    Article  Google Scholar 

  13. Christensen BB, Foldager CB, Jensen J, Jensen NC, Lind M. Poor osteochondral repair by a biomimetic collagen scaffold: 1- to 3-year clinical and radiological follow-up. Knee Surg Sports Traumatol Arthrosc. 2016;24:2380–7.

    Article  Google Scholar 

  14. Marcacci M, Zaffagnini S, Kon E, Marcheggiani Muccioli GM, Di Martino A, Di Matteo B, et al. Unicompartmental osteoarthritis: an integrated biomechanical and biological approach as alternative to metal resurfacing. Knee Surg Sports Traumatol Arthrosc. 2013;21:2509–17.

    Article  CAS  Google Scholar 

  15. Ito K, Aoyama T, Fukiage K, Otsuka S, Furu M, Jin Y, et al. A novel method to isolate mesenchymal stem cells from bone marrow in a closed system using a device made by nonwoven fabric. Tissue Eng Part C Methods. 2010;16:81–91.

    Article  CAS  Google Scholar 

  16. Otsuru S, Hofmann TJ, Olson TS, Dominici M, Horwitz EM. Improved isolation and expansion of bone marrow mesenchymal stromal cells using a novel marrow filter device. Cytotherapy. 2013;15:146–53.

    Article  CAS  Google Scholar 

  17. Dawson JI, Smith JO, Aarvold A, Ridgway JN, Curran SJ, Dunlop DG, et al. Enhancing the osteogenic efficacy of human bone marrow aspirate: concentrating osteoprogenitors using wave-assisted filtration. Cytotherapy. 2013;15:242–52.

    Article  CAS  Google Scholar 

  18. Filardo G, Drobnic M, Perdisa F, Kon E, Hribernik M, Marcacci M. Fibrin glue improves osteochondral scaffold fixation: study on the human cadaveric knee exposed to continuous passive motion. Osteoarthritis Cartilage. 2014;22:557–65.

    Article  CAS  Google Scholar 

  19. Cuthbert R, Boxall SA, Tan HB, Giannoudis PV, McGonagle D, Jones E. Single-platform quality control assay to quantify multipotential stromal cells in bone marrow aspirates prior to bulk manufacture or direct therapeutic use. Cytotherapy. 2012;14:431–40.

    Article  CAS  Google Scholar 

  20. Dominici M, Le Blanc K, Mueller I, Slaper-Cortenbach I, Marini F, Krause D, et al. Minimal criteria for defining multipotent mesenchymal stromal cells. The International Society for Cellular Therapy position statement. Cytotherapy. 2006;8:315–7.

    Article  CAS  Google Scholar 

  21. Knee Injury and Osteoarthritis Outcome Score (KOOS), Slovenian version LK1.0. 2007. http://www.koos.nu/KOOSSlovenian.pdf. Accessed 27 Dec 2016.

  22. Brittberg M, Winalski CS. Evaluation of cartilage injuries and repair. J Bone Joint Surg Am. 2003;85:58–69.

    Article  Google Scholar 

  23. Nooeaid P, Salih V, Beier JP, Boccaccini AR. Osteochondral tissue engineering: scaffolds, stem cells and applications. J Cell Mol Med. 2012;16:2247–70.

    Article  CAS  Google Scholar 

  24. Murray IR, Chahla J, Safran MR, Krych AJ, Saris DBF, Caplan AI, et al. International expert consensus on a cell therapy communication tool: DOSES. J Bone Joint Surg Am. 2019;101:904–11.

    Article  Google Scholar 

  25. Hegde V, Shonuga O, Ellis S, Fragomen A, Kennedy J, Kudryashov V, et al. A prospective comparison of 3 approved systems for autologous bone marrow concentration demonstrated nonequivalency in progenitor cell number and concentration. J Orthop Trauma. 2014;28:591–8.

    Article  Google Scholar 

  26. Filardo G, Kon E, Di Martino A, Busacca M, Altadonna G, Marcacci M. Treatment of knee osteochondritis dissecans with a cell-free biomimetic osteochondral scaffold. Am J Sports Med. 2013;41:1786–93.

    Article  Google Scholar 

  27. Drobnič M, Martinčič D, Merkač J, Radosavljevič D. Survival rates of various ACI grafts and concomitant procedures. A prospective single-center study over 15 years. In: Book of Abstracts. 13th World Congress of the International Cartilage Repair Society; 2016 Sep 23–27; Sorrento, Italy. ICRS; 2016.

  28. Gobbi A, Karnatzikos G, Sankineani SR. One-step surgery with multipotent stem cells for the treatment of large full-thickness chondral defects of the knee. Am J Sports Med. 2014;42:648–57.

    Article  Google Scholar 

  29. Gobbi A, Chaurasia S, Karnatzikos G, Nakamura N. Matrix-induced autologous chondrocyte implantation versus multipotent stem cells for the treatment of large patellofemoral chondral lesions: a nonrandomized prospective trial. Cartilage. 2015;6:82–97.

    Article  CAS  Google Scholar 

  30. Enea D, Cecconi S, Calcagno S, Busilacchi A, Manzotti S, Gigante A. One-step cartilage repair in the knee: collagen-covered microfracture and autologous bone marrow concentrate. A pilot study. Knee. 2015;22:30–5.

    Article  CAS  Google Scholar 

  31. Skowroński J, Skowroński R, Rutka M. Large cartilage lesions of the knee treated with bone marrow concentrate and collagen membrane–results. Ortop Traumatol Rehabil. 2013;15:69–76.

    Article  Google Scholar 

  32. Chahla J, Dean CS, Moatshe G, Pascual-Garrido C, Serra Cruz R, LaPrade RF. Concentrated bone marrow aspirate for the treatment of chondral injuries and osteoarthritis of the knee: a systematic review of outcomes. Orthop J Sports Med. 2016;4:2325967115625481.

    PubMed  PubMed Central  Google Scholar 

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Acknowledgement

The authors acknowledge the financial support from the UKC-LJ Institutional research funding (No. 20150156).

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Authors and Affiliations

Authors

Contributions

MK and MD conceived and designed the study. MV, JV and MD acquired the data, MV, AB and MD interpreted and analysed the data. MV, JV, AB and MD drafted the article and MK revised it critically for the important intellectual content. All authors approved the final version of the article to be published.

Corresponding author

Correspondence to Matija Veber.

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Conflict of interest

Educell Ltd., Trzin, Slovenia (co-authors MV, MK, AB) is a commercial cell and tissue institution that is providing separated MSCs and other advanced cell therapies. MD is a clinical consultant to Fin-Ceramica, Faenza, Italy.

Ethical statement

All procedures performed in studies involving human participants were in accordance with the ethical standards of the national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards. The study protocol was approved by the National Medical Ethics Committee (No. 0120-14/2016-2). Informed consent was confirmed by the National Medical Ethics Committee.

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Veber, M., Vogler, J., Knežević, M. et al. Combination of Filtered Bone Marrow Aspirate and Biomimetic Scaffold for the Treatment of Knee Osteochondral Lesions: Cellular and Early Clinical Results of a Single Centre Case Series. Tissue Eng Regen Med 17, 375–386 (2020). https://doi.org/10.1007/s13770-020-00253-9

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