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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

      Purpose

      To analyze the results of the use of intra-articular cultured autologous bone marrow–derived mesenchymal stem cell (MSC) injections in conjunction with microfracture and medial opening-wedge high tibial osteotomy (HTO).

      Methods

      Fifty-six knees in 56 patients with unicompartmental osteoarthritic knees and genu varum were randomly allocated to the cell-recipient group (n = 28) or control group (n = 28). Patients who had a joint line congruity angle of more than 2°, malalignment of the knee from femoral causes, a fixed flexion deformity, or age older than 55 years were excluded. All patients underwent HTO and microfracture. The cell-recipient group received intra-articular injection of cultured MSCs with hyaluronic acid 3 weeks after surgery, whereas the control group only received hyaluronic acid. The primary outcome measure was the International Knee Documentation Committee (IKDC) score at intervals of 6 months, 1 year, and 2 years postoperatively. Secondary outcome measures were Tegner and Lysholm clinical scores and 1-year postoperative Magnetic Resonance Observation of Cartilage Repair Tissue (MOCART) scores.

      Results

      The median age of the patients was 51 years, with a mean body mass index of 23.85. Both treatment arms achieved improvements in Tegner, Lysholm, and IKDC scores. After adjustment for age, baseline scores, and time of evaluation, the cell-recipient group showed significantly better scores. The effect of treatment showed an added improvement of 7.65 (95% confidence interval [CI], 3.04 to 12.26; P = .001) for IKDC scores, 7.61 (95% CI, 1.44 to 13.79; P = .016) for Lysholm scores, and 0.64 (95% CI, 0.10 to 1.19; P = .021) for Tegner scores. Magnetic resonance imaging scans performed 1 year after surgical intervention showed significantly better MOCART scores for the cell-recipient group. The age-adjusted mean difference in MOCART score was 19.6 (95% CI, 10.5 to 28.6; P < .001).

      Conclusions

      Intra-articular injection of cultured MSCs is effective in improving both short-term clinical and MOCART outcomes in patients undergoing HTO and microfracture for varus knees with cartilage defects.

      Level of Evidence

      Level II, randomized controlled trial.
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      References

        • Coventry M.B.
        • Ilstrup D.M.
        • Wallrichs S.L.
        Proximal tibial osteotomy: A critical long-term study of eighty-seven cases.
        J Bone Joint Surg Am. 1993; 75: 196-201
        • Luites J.W.
        • Brinkman J.M.
        • Wymenga A.B.
        • van Heerwaarden R.J.
        Fixation stability of opening- versus closing-wedge high tibial osteotomy: A randomised clinical trial using radiostereometry.
        J Bone Joint Surg Br. 2009; 91: 1459-1465
        • Akizuki S.
        • Yasukawa Y.
        • Takizawa T.
        Does arthroscopic abrasion arthroplasty promote cartilage regeneration in osteoarthritic knees with eburnation? A prospective study of high tibial osteotomy with abrasion arthroplasty versus high tibial osteotomy alone.
        Arthroscopy. 1997; 13: 9-17
        • LaPrade R.F.
        • Bursch L.S.
        • Olson E.J.
        • Havlas V.
        • Carlson C.S.
        Histologic and immunohistochemical characteristics of failed articular cartilage resurfacing procedures for osteochondritis of the knee: A case series.
        Am J Sports Med. 2008; 36: 360-368
        • Mithoefer K.
        • Williams III, R.J.
        • Warren R.F.
        • et al.
        The microfracture technique for the treatment of articular cartilage lesions in the knee. A prospective cohort study.
        J Bone Joint Surg Am. 2005; 87: 1911-1920
        • Wakitani S.
        • Imoto K.
        • Yamamoto T.
        • Saito M.
        • Murata N.
        • Yoneda M.
        Human autologous culture expanded bone marrow mesenchymal cell transplantation for repair of cartilage defects in osteoarthritic knees.
        Osteoarthritis Cartilage. 2002; 10: 199-206
        • McIlwraith C.W.
        • Frisbie D.D.
        • Rodkey W.G.
        • et al.
        Evaluation of intraarticular mesenchymal stem cells to augment healing of microfractured chondral defects.
        Arthroscopy. 2011; 27: 1552-1561
        • Brittberg M.
        • Winalski C.S.
        Evaluation of cartilage injuries and repair.
        J Bone Joint Surg Am. 2003; 85: 58-69
        • Steadman J.R.
        • Rodkey W.G.
        • Rodrigo J.J.
        Microfracture: Surgical technique and rehabilitation to treat chondral defects.
        Clin Orthop Relat Res. 2001; 391: S362-S369
        • Martin I.
        • Baldomero H.
        • Bocelli-Tyndall C.
        • Passweg J.
        • Saris D.
        • Tyndall A.
        The survey on cellular and engineered tissue therapies in Europe in 2010.
        Tissue Eng Part A. 2012; 18: 2268-2279
        • Simmons P.J.
        • Torok-Storb B.
        Identification of stromal cell precursors in human bone marrow by a novel monoclonal antibody, STRO-1.
        Blood. 1991; 78: 55-62
        • Dominici M.
        • Le Blanc K.
        • Mueller I.
        • et al.
        Minimal criteria for defining multipotent mesenchymal stromal cells. The International Society for Cellular Therapy position statement.
        Cytotherapy. 2006; 8: 315-317
        • Marlovits S.
        • Striessnig G.
        • Resinger C.T.
        • et al.
        Definition of pertinent parameters for the evaluation of articular cartilage repair tissue with high-resolution magnetic resonance imaging.
        Eur J Radiol. 2004; 52: 310-319
        • Centeno C.J.
        • Busse D.
        • Kisiday J.
        • Keohan C.
        • Freeman M.
        • Karli D.
        Increased knee cartilage volume in degenerative joint disease using percutaneously implanted, autologous mesenchymal stem cells.
        Pain Physician. 2008; 11: 343-353
        • Lee K.B.
        • Hui J.H.
        • Song I.C.
        • Ardany L.
        • Lee E.H.
        Injectable mesenchymal stem cell therapy for large cartilage defects—A porcine model.
        Stem Cells. 2007; 25: 2964-2971
        • Nejadnik H.
        • Hui J.H.
        • Feng Choong E.P.
        • Tai B.C.
        • Lee E.H.
        Autologous bone marrow-derived mesenchymal stem cells versus autologous chondrocyte implantation: An observational cohort study.
        Am J Sports Med. 2010; 38: 1110-1116
        • Sato M.
        • Uchida K.
        • Nakajima H.
        • et al.
        Direct transplantation of mesenchymal stem cells into the knee joints of Hartley strain guinea pigs with spontaneous osteoarthritis.
        Arthritis Res Ther. 2012; 14: R31
        • Saw K.Y.
        • Hussin P.
        • Loke S.C.
        • et al.
        Articular cartilage regeneration with autologous marrow aspirate and hyaluronic acid: An experimental study in a goat model.
        Arthroscopy. 2009; 25: 1391-1400
        • Agung M.
        • Ochi M.
        • Yanada S.
        • et al.
        Mobilization of bone marrow-derived mesenchymal stem cells into the injured tissues after intraarticular injection and their contribution to tissue regeneration.
        Knee Surg Sports Traumatol Arthrosc. 2006; 14: 1307-1314
        • Koga H.
        • Shimaya M.
        • Muneta T.
        • et al.
        Local adherent technique for transplanting mesenchymal stem cells as a potential treatment of cartilage defect.
        Arthritis Res Ther. 2008; 10: R84
        • Sterett W.I.
        • Steadman J.R.
        • Huang M.J.
        • Matheny L.M.
        • Briggs K.K.
        Chondral resurfacing and high tibial osteotomy in the varus knee: Survivorship analysis.
        Am J Sports Med. 2010; 38: 1420-1424
        • Miller B.S.
        • Joseph T.A.
        • Barry E.M.
        • Rich V.J.
        • Sterett W.I.
        Patient satisfaction after medial opening high tibial osteotomy and microfracture.
        J Knee Surg. 2007; 20: 129-133
        • Krych A.J.
        • Harnly H.W.
        • Rodeo S.A.
        • Williams III, R.J.
        Activity levels are higher after osteochondral autograft transfer mosaicplasty than after microfracture for articular cartilage defects of the knee: A retrospective comparative study.
        J Bone Joint Surg Am. 2012; 94: 971-978
        • Carey J.L.
        Fibrocartilage following microfracture is not as robust as native articular cartilage: Commentary on an article by Aaron J. Krych, MD, et al.: “Activity levels are higher after osteochondral autograft transfer mosaicplasty than after microfracture for articular cartilage defects of the knee. A retrospective comparative study.”.
        J Bone Joint Surg Am. 2012; 94: e80
        • Kobayashi T.
        • Ochi M.
        • Yanada S.
        • et al.
        A novel cell delivery system using magnetically labeled mesenchymal stem cells and an external magnetic device for clinical cartilage repair.
        Arthroscopy. 2008; 24: 69-76
        • Kobayashi T.
        • Ochi M.
        • Yanada S.
        • et al.
        Augmentation of degenerated human cartilage in vitro using magnetically labeled mesenchymal stem cells and an external magnetic device.
        Arthroscopy. 2009; 25: 1435-1441
        • Hori J.
        • Deie M.
        • Kobayashi T.
        • Yasunaga Y.
        • Kawamata S.
        • Ochi M.
        Articular cartilage repair using an intra-articular magnet and synovium-derived cells.
        J Orthop Res. 2011; 29: 531-538