Regeneration Using Adipose-Derived Stem Cell Sheets in a Rabbit Meniscal Defect Model Improves Tensile Strength and Load Distribution Function of the Meniscus at 12 Weeks


      The purpose of this study was to evaluate the mechanical properties, such as the tensile strength and load distribution function, of the meniscus tissue regenerated using adipose-derived stem cell (ADSC) sheets in a rabbit meniscal defect model.


      ADSC sheets were prepared from adipose tissue of rabbits. The anterior half of the medial meniscus was removed from both knees. One knee was transplanted with an ADSC sheet; the contralateral knee was closed without transplantation. Mechanical tests were performed at 4 and 12 weeks posttransplantation. In the tensile test, tensile force was applied to the entire medial meniscus, including the normal area (n = 10/group). Compression tests were performed on the entire knee, with soft tissues other than the ligament removed. A pressure-sensitive film was inserted under the medial meniscus and a 40-N load was applied (n = 5/group).


      In the tensile test, the elastic modulus in ADSC-treated knees was higher at 12 weeks (ADSC: 70.30 ± 18.50 MPa, control: 43.71 ± 7.11 MPa, P = .009). The ultimate tensile strength (UTS) in ADSC-treated knees at 12 weeks was also higher (ADSC: 22.69 ± 5.87 N, control: 15.45 ± 4.08 N, P = .038). In the compression test, the contact area was larger in the ADSC group at 4 weeks (ADSC: 31.60 ± 8.17 mm2, control: 20.33 ± 2.86 mm2, P = .024) and 12 weeks (ADSC: 41.07 ± 6.09 mm2, control: 30.53 ± 5.47 mm2, P = .04). Peak pressure was significantly lower in ADSC-treated knees at 12 weeks (ADSC: 11.91 ± 1.03 MPa, control: 15.53 ± 2.3 MPa, P = .002).


      The regenerated meniscus tissue, 12 weeks after transplantation of the ADSC sheets into the meniscal defect area, had high elastic modulus and UTS. In the meniscus-tibia compartment, the contact area was large and the peak pressure was low.

      Clinical Relevance

      ADSC sheets promoted regeneration of meniscus. ADSC sheet transplantation for meniscal defects could be an effective regenerative therapy.
      To read this article in full you will need to make a payment

      Purchase one-time access:

      Academic & Personal: 24 hour online accessCorporate R&D Professionals: 24 hour online access
      One-time access price info
      • For academic or personal research use, select 'Academic and Personal'
      • For corporate R&D use, select 'Corporate R&D Professionals'


      Subscribe to Arthroscopy
      Already a print subscriber? Claim online access
      Already an online subscriber? Sign in
      Institutional Access: Sign in to ScienceDirect


        • Ashton B.A.
        • Allen T.D.
        • Howlett C.R.
        • Eaglesom C.C.
        • Hattori A.
        • Owen M.
        Formation of bone and cartilage by marrow stromal cells in diffusion chambers in vivo.
        Clin Orthop Relat Res. 1980; 151: 294-307
        • Zhang Z.Z.
        • Zhou Y.F.
        • Li W.P.
        • et al.
        Local administration of magnesium promotes meniscal healing through homing of endogenous stem cells: A proof-of-concept study.
        Am J Sports Med. 2019; 47: 954-967
        • Chang C.H.
        • Chen C.H.
        • Liu H.W.
        • et al.
        Bioengineered periosteal progenitor cell sheets to enhance tendon-bone healing in a bone tunnel.
        Biomed J. 2012; 35: 473-480
        • Hevesi M.
        • LaPrade M.
        • Saris D.B.F.
        • Krych A.J.
        Stem cell treatment for ligament repair and reconstruction.
        Curr Rev Musculoskelet Med. 2019; 12: 446-450
        • Zuk P.A.
        • Zhu M.
        • Mizuno H.
        • et al.
        Multilineage cells from human adipose tissue: Implications for cell-based therapies.
        Tissue Eng. 2001; 7: 211-228
        • Sterodimas A.
        • de Faria J.
        • Nicaretta B.
        • Pitanguy I.
        Tissue engineering with adipose-derived stem cells (ADSCs): Current and future applications.
        J Plast Reconstr Aesthet Surg. 2010; 63: 1886-1892
        • Zhang J.
        • Zhou S.
        • Zhou Y.
        • et al.
        Adipose-derived mesenchymal stem cells (ADSCs) with the potential to ameliorate platelet recovery, enhance megakaryopoiesis, and inhibit apoptosis of bone marrow cells in a mouse model of radiation-induced thrombocytopenia.
        Cell Transplant. 2016; 25: 261-273
        • Crisan M.
        • Yap S.
        • Casteilla L.
        • et al.
        A perivascular origin for mesenchymal stem cells in multiple human organs.
        Cell Stem Cell. 2008; 3: 301-313
        • Fang X.
        • Murakami H.
        • Demura S.
        • et al.
        A novel method to apply osteogenic potential of adipose derived stem cells in orthopaedic surgery.
        PLoS One. 2014; 9: e88874
        • Takata Y.
        • Nakase J.
        • Shimozaki K.
        • Asai K.
        • Tsuchiya H.
        Autologous adipose-derived stem cell sheet has meniscus regeneration-promoting effects in a rabbit model.
        Arthroscopy. 2020; 36: 2698-2707
        • Leumann A.
        • Fortuna R.
        • Leonard T.
        • Valderrabano V.
        • Herzog W.
        Tibiofemoral loss of contact area but no changes in peak pressures after meniscectomy in a Lapine in vivo quadriceps force transfer model.
        Knee Surg Sports Traumatol Arthrosc. 2015; 23: 65-73
        • Nakajima T.
        • Tada K.
        • Nakada M.
        • Matsuta M.
        • Tsuchiya H.
        Facilitatory effects of artificial nerve filled with adipose-derived stem cell sheets on peripheral nerve regeneration: An experimental study.
        J Orthop Sci. 2021; 26: 1113-1118
        • Takagi T.
        • Kabata T.
        • Hayashi K.
        • et al.
        Periodic injections of adipose-derived stem cell sheets attenuate osteoarthritis progression in an experimental rabbit model.
        BMC Musculoskelet Disord. 2020; 21: 691
        • Gao S.
        • Chen M.
        • Wang P.
        • et al.
        An electrospun fiber reinforced scaffold promotes total meniscus regeneration in rabbit meniscectomy model.
        Acta Biomater. 2018; 73: 127-140
        • Li Y.
        • Chen M.
        • Zhou W.
        • et al.
        Cell-free 3D wet-electrospun PCL/silk fibroin/Sr(2+) scaffold promotes successful total meniscus regeneration in a rabbit model.
        Acta Biomater. 2020; 113: 196-209
        • Beamer B.S.
        • Masoudi A.
        • Walley K.C.
        • et al.
        Analysis of a new all-inside versus inside-out technique for repairing radial meniscal tears.
        Arthroscopy. 2015; 31: 293-298
        • Zhang Z.Z.
        • Wang S.J.
        • Zhang J.Y.
        • et al.
        3D-printed poly(ε-caprolactone) scaffold augmented with mesenchymal stem cells for total meniscal substitution: A 12- and 24-week animal study in a rabbit model.
        Am J Sports Med. 2017; 45: 1497-1511
        • Sawatsky A.
        • Bourne D.
        • Horisberger M.
        • Jinha A.
        • Herzog W.
        Changes in patellofemoral joint contact pressures caused by vastus medialis muscle weakness.
        Clin Biomech (Bristol, Avon). 2012; 27: 595-601
        • Leumann A.
        • Fortuna R.
        • Leonard T.
        • Valderrabano V.
        • Herzog W.
        Dynamic in-vivo force transfer in the lapine knee loaded by quadriceps muscle contraction.
        Clin Biomech (Bristol, Avon). 2013; 28: 199-204
        • Tissakht M.
        • Ahmed A.M.
        • Chan K.C.
        Calculated stress-shielding in the distal femur after total knee replacement corresponds to the reported location of bone loss.
        J Orthop Res. 1996; 14: 778-785
        • Zhu W.
        • Chern K.Y.
        • Mow V.C.
        Anisotropic viscoelastic shear properties of bovine meniscus.
        Clin Orthop Relat Res. 1994; : 34-45
        • Newman A.P.
        • Anderson D.R.
        • Daniels A.U.
        • Dales M.C.
        Mechanics of the healed meniscus in a canine model.
        Am J Sports Med. 1989; 17: 164-175
        • Proctor C.S.
        • Schmidt M.B.
        • Whipple R.R.
        • Kelly M.A.
        • Mow V.C.
        Material properties of the normal medial bovine meniscus.
        J Orthop Res. 1989; 7: 771-782
        • Fairbank T.J.
        Knee joint changes after meniscectomy.
        J Bone Joint Surg Br. 1948; 30: 664-670
        • Fukubayashi T.
        • Kurosawa H.
        The contact area and pressure distribution pattern of the knee: A study of normal and osteoarthrotic knee joints.
        Acta Orthop Scand. 1980; 51: 871-879
        • von Lewinski G.
        • Stukenborg-Colsman C.
        • Ostermeier S.
        • Hurschler C.
        Experimental measurement of tibiofemoral contact area in a meniscectomized ovine model using a resistive pressure measuring sensor.
        Ann Biomed Eng. 2006; 34: 1607-1614
        • Petty C.A.
        • Lubowitz J.H.
        Does arthroscopic partial meniscectomy result in knee osteoarthritis? A systematic review with a minimum of 8 years' follow-up.
        Arthroscopy. 2011; 27: 419-424
        • Pengas I.P.
        • Assiotis A.
        • Nash W.
        • Hatcher J.
        • Banks J.
        • McNicholas M.J.
        Total meniscectomy in adolescents: A 40-year follow-up.
        J Bone Joint Surg Br. 2012; 94: 1649-1654
        • Roos H.
        • Laurén M.
        • Adalberth T.
        • Roos E.M.
        • Jonsson K.
        • Lohmander L.S.
        Knee osteoarthritis after meniscectomy: Prevalence of radiographic changes after twenty-one years, compared with matched controls.
        Arthritis Rheum. 1998; 41: 687-693
        • Kääb M.J.
        • Ito K.
        • Clark J.M.
        • Nötzli H.P.
        The acute structural changes of loaded articular cartilage following meniscectomy or ACL-transection.
        Osteoarthritis Cartilage. 2000; 8: 464-473
        • Uysal A.C.
        • Mizuno H.
        Tendon regeneration and repair with adipose derived stem cells.
        Curr Stem Cell Res Ther. 2010; 5: 161-167
        • Yu J.
        • Tu Y.K.
        • Tang Y.B.
        • Cheng N.C.
        Stemness and transdifferentiation of adipose-derived stem cells using L-ascorbic acid 2-phosphate-induced cell sheet formation.
        Biomaterials. 2014; 35: 3516-3526
        • Li M.
        • Ma J.
        • Gao Y.
        • Yang L.
        Cell sheet technology: A promising strategy in regenerative medicine.
        Cytotherapy. 2019; 21: 3-16
        • Kashiyama N.
        • Kormos R.L.
        • Matsumura Y.
        • et al.
        Adipose-derived stem cell sheet under an elastic patch improves cardiac function in rats after myocardial infarction.
        J Thorac Cardiovasc Surg. 2020; 163: 261-272
        • Kanai N.
        • Yamato M.
        • Okano T.
        Cell sheets engineering for esophageal regenerative medicine.
        Ann Transl Med. 2014; 2: 28
        • Huayllani M.T.
        • Sarabia-Estrada R.
        • Restrepo D.J.
        • et al.
        Adipose-derived stem cells in wound healing of full-thickness skin defects: a review of the literature.
        J Plast Surg Hand Surg. 2020; 54: 263-279
        • Matsumoto T.
        • Sato Y.
        • Kobayashi T.
        • et al.
        Adipose-derived stem cell sheets improve early biomechanical graft strength in rabbits after anterior cruciate ligament reconstruction.
        Am J Sports Med. 2021; 49: 3508-3518
      1. Asai K, Nakase J, Yoshioka K, Yoshimizu R, Kimura M, Tsuchiya H. Adipose-derived stem cell sheets promote meniscus regeneration regardless of whether the defect involves the inner half or the whole width of the anterior half of the medial meniscus in a rabbit model [published online March 4, 2022]. Arthroscopy.

        • Neo P.Y.
        • See E.Y.
        • Toh S.L.
        • Goh J.C.
        Temporal profiling of the growth and multi-lineage potentiality of adipose tissue-derived mesenchymal stem cells cell-sheets.
        J Tissue Eng Regen Med. 2016; 10: 564-579
        • Tissakht M.
        • Ahmed A.M.
        Tensile stress-strain characteristics of the human meniscal material.
        J Biomech. 1995; 28: 411-422
        • Jones R.S.
        • Keene G.C.
        • Learmonth D.J.
        • et al.
        Direct measurement of hoop strains in the intact and torn human medial meniscus.
        Clin Biomech (Bristol, Avon). 1996; 11: 295-300
        • Koga H.
        • Nakamura T.
        • Katagiri H.
        • et al.
        Two-year outcomes after meniscoplasty by capsular advancement with the application of arthroscopic centralization technique for lateral compartment knee osteoarthritis.
        Am J Sports Med. 2020; 48: 3154-3162