Background: The relationship between biological tissue healing following knee injury or surgery and long-term clinical outcome has come to the forefront of sports medicine practice. This has led many knee surgeons to incorporate biologically mediated healing factors into the management of knee injuries. In particular, the clinical use of mesenchymal stem cells has opened new horizons.
Evidence Acquisition: Relevant studies were identified through a search of PubMed from January 2000 to April 2011, combining the term mesenchymal stem cells with articular cartilage, anterior cruciate ligament, and meniscus. Relevant citations from the reference lists of selected studies were also reviewed.
Results: Knee injury treatment with mesenchymal stem cells shows potential. Most reports represent animal model studies; few advances have been translated to human clinical applications.
Conclusion: Mesenchymal stem cell use to promote healing following knee injury is likely to increase. There are scientific methodological concerns and ethical and legal issues regarding mesenchymal stem cell use for treating knee injuries.
AdachiNSatoKUsasA. Muscle derived, cell based ex vivo gene therapy for treatment of full thickness articular cartilage defects. J Rheumatol. 2002;29:1920-1930.
2.
AndoWTateishiKHartDA. Cartilage repair using in vitro generated scaffold-free tissue-engineered construct derived from porcine mesenchymal stem cells. Biomaterials. 2007;28:5462-5470.
3.
AndoWTateishiKKatakaiD. In vitro generation of a scaffold-free tissue engineered construct (TEC) derived from human synovial mesenchymal stem cells: Biological and mechanical properties and further chondrogenic potential. Tissue Eng Part A. 2008;14:2041-2049.
4.
AndrianoKPTabataYIkadaYHellerJ. In vitro and in vivo comparison of bulk and surface hydrolysis in absorbable polymer scaffolds for tissue engineering. J Biomed Mater Res. 1999;48:602-612.
5.
AshtonBAAllenTDHowlettCR. Formation of bone and cartilage by marrow stromal cells in diffusion chambers in vivo. Clin Orthop Relat Res. 1980;151:294-307.
6.
BarryFP. Mesenchymal stem cell therapy in joint disease. In: BockGGoodeJ, eds. Tissue Engineering of Cartilage and Bone. Vol 249. West Sussex, England: John Wiley & Sons; 2002:86-102.
7.
BarryFBoyntonRELiuB. Chondrogenic differentiation of mesenchymal stem cells from the bone marrow: differentiation-dependent gene expression of matrix components. Exp Cell Res. 2001;286:189-200.
8.
BernardoMEZaffaroniNNovaraF. Human bone marrow derived mesenchymal stem cells do not undergo transformation after long-term in vitro culture and do not exhibit telomere maintenance mechanisms. Cancer Res. 2007;67:9142-9149.
9.
BongsoALeeEH. Stem cells: their definition, classification and sources. In: BongsoALeeEH eds. Stems Cells: From Bench to Bedside. Singapore: World Scientific Publishing, 2005.
10.
BrunPAbatangeloGRadiceM. Chondrocyte aggregation and reorganization into three-dimensional scaffolds. J Biomed Mater Res. 1999;46:337-346.
11.
CaoBZhengBJankowskiRJ. Muscle stem cells differentiate into haematopoietic lineages but retain myogenic potential. Nat Cell Biol. 2003;5:640-646.
12.
CaplanAI. Mesenchymal stem cells: the past, the present, the future. Cartilage. 2010;1:6-9.
13.
ChenJWangCLuS. In vivo chondrogenesis of adult bone-marrow-derived autologous mesenchymal stem cells. Cell Tissue Res. 2005;319:429-438.
14.
ColterDCSekiyaIProckopDJ. Identification of a subpopulation of rapidly self-renewing and multipotential adult stem cells in colonies of human marrow stromal cells. Proc Natl Acad Sci U S A. 2001;98:7841-7845.
15.
CsakiCMatisUMobasheriAYeHShakibaeiM. Chondrogenesis, osteogenesis and adipogenesis of canine mesenchymal stem cells: a biochemical, morphological and ultrastructural study. Histochem Cell Biol. 2007;128:507-520.
16.
De BariCDell’AccioFLuytenFP. Failure of in vitro-differentiated mesenchymal stem cells from the synovial membrane to form ectopic stable cartilage in vivo. Arthritis Rheum. 2004;50:142-150.
17.
De BariCDell’AccioFLuytenFP. Human periosteum-derived cells maintain phenotypic stability and chondrogenic potential throughout expansion regardless of donor age. Arthritis Rheum. 2001;44:85-95.
18.
De BariCDell’AccioFTylzanowskiPLuytenFP. Multipotent mesenchymal stem cells from adult human synovial membrane. Arthritis Rheum. 2001;44:1928-1942.
19.
DickerALe BlancKAstromG. Functional studies of mesenchymal stem cells derived from adult human adipose tissue. Exp Cell Res. 2005;308:283-290.
20.
DickhutAGottwaldESteckEHeiselCRichterW. Chondrogenesis of mesenchymal stem cells in gel-like biomaterials in vitro and in vivo. Front Biosci. 2008;13:4517-4528.
21.
DragooJLSamimiBZhuM. Tissue-engineered cartilage and bone using stem cells from human infrapatellar fat pads. J Bone Joint Surg Br. 2003;85:740-747.
22.
DuttonAChoongPFGohJCHLeeEHHuiJH. Enhancement of meniscal repair in the avascular zone using mesenchymal stem cells in a porcine model. J Bone Joint Surg Br. 2010;92:169-175.
23.
FischerJDickhutARickertMRichterW. Human articular chondrocytes secrete parathyroid hormone-related protein and inhibit hypertrophy of mesenchymal stem cells in coculture during chondrogenesis. Arthritis Rheum. 2010;62:2696-2706.
24.
FortierLAPotterHGRickeyEJ. Concentrated bone marrow aspirate improves full-thickness cartilage repair compared with microfracture in the equine model. J Bone Joint Surg Am. 2010;92:1927-1937.
25.
FreyriaAMCortialDRonziereMCGuerretSHerbageD. Influence of medium composition, static and stirred conditions on the proliferation of and matrix protein expression of bovine articular chondrocytes cultures in a 3D collagen scaffold. Biomaterials. 2004;25:687-697.
26.
FriedensteinAJPiaetezky-ShapiroIIPetrakovaKV. Osteogenesis in transplants of bone marrow cells. J Embryol Exp Morphol. 1966;16:381-390.
27.
FukumotoTSperlingJWSanyalA. Combined effects of insulin-like growth factor-1 and transforming growth factor-beta1 on periosteal mesenchymal cells during chondrogenesis in vitro. Osteoarthritis Cartilage. 2003;11:55-64.
28.
GeZGohCHJLeeEH. The effects of bone marrow-derived mesenchymal stem cells and fascia wrap application to anterior cruciate ligament tissue engineering. Cell Transplant. 2005;14:763-773.
29.
HaleemAMEl SingergyAASabryD. The clinical use of human culture-expanded autologous bone marrow mesenchymal stem cells transplanted on platelet-rich fibrin glue in the treatment of articular cartilage defects: A pilot study and preliminary results. Cartilage. 2010;1:253-262.
30.
HengBCCaoTLeeEH. Directing stem cell differentiation into the chondrogenic lineage in vitro. Stem Cells. 2004;22:1152-1167.
31.
HommingaGNBumaPKootHWvan der KraanPMvan den BergWB. Chondrocyte behavior in fibrin glue in vitro. Acta Orthop Scand. 1993;64:441-445.
32.
HorieMSekiyaIMunetaT. Intra-articular injected stem cells differentiate into meniscal cells directly and promote meniscal regeneration without mobilisation to distant organs in rat massive meniscal defect. Stem Cells. 2009;27:878-887.
33.
HuangJIKazmiNDurbhaskulaMMHeringTMYooJUJohnstoneB. Chondrogenic potential of progenitor cells derived from human bone marrow and adipose tissue: a patient-matched comparison. J Orthop Res. 2005;23:1383-1389.
34.
HuiJHChenFThambyahALeeEH. Treatment of chondral lesions in advanced osteochondritis dissecans: a comparative study of the efficacy of chondrocytes, mesenchymal stem cells, periosteal graft, and mosaicplasty (osteochondral autograft) in animal models. J Pediatric Orthop. 2004;24:427-433.
35.
HunzikerEBRosenbergLC. Repair of partial-thickness defects in articular cartilage: cell recruitment from the synovial membrane. J Bone Joint Surg Am. 1996;78:721-733.
36.
IchinoseSYamagataKSekiyaIMunetaTTagamiM. Detailed examination of cartilage formation and endochondral ossification using human mesenchymal stem cells. Clin Exp Pharmacol Physiol. 2005;32:561-570.
37.
ImGIKimDYShinJHHyunCWChoWH. Repair of cartilage defect in the rabbit with cultured mesenchymal stem cells from bone marrow. J Bone Joint Surg Br. 2001;83:289-294.
38.
IwasakiMNakataKNakaharaH. Transforming growth factor beta 1 stimulates chondrogenesis and inhibits osteogenesis in high density culture of periosteum-derived cells. Endocrinology. 1993;132:1603-1608.
39.
IzutaYOchiMAdachiNDeieMYamasakiTShinomiyaR. Meniscus repair using bone marrow-derived mesenchymal stem cells: experimental study using green fluorescent protein transgenic rats. Knee. 2005;12:217-223.
JakobRP. AMIC technique for cartilage repair: a single-step surgical intervention as compared to other methods. Eur Cell Mater. 2006;12(suppl 1):26.
42.
JohnstoneBHeringTMCaplanALGoldbergVMJooJU. In vitro chondrogenesis of bone marrow-derived mesenchymal progenitor cells. Exp Cell Res. 1998;238:265-272.
43.
KanayaADeieMAdachiNNishimoriMYanadaSOchiM. Intra-articular injection of mesenchymal stromal cells in partially torn anterior cruciate ligaments in a rat model. Arthroscopy. 2007;23:610-617.
44.
KobayashiTOchiMYanadaS. A novel cell delivery system using magnetically labelled mesenchymal stem cells and an external magnetic device for clinical cartilage repair. Arthroscopy. 2008;24:69-76.
45.
KobayashiTWatanabeHYanagawaT. Motility and growth of human bone-marrow mesenchymal stem cells during ex vivo expansion in autologous serum. J Bone Joint Surg Br. 2005;87:1426-1433.
46.
KogaHEngebretsenLBrinchmannJEMunetaTSekiyaI. Mesenchymal stem cell based therapy for cartilage repair: a review. Knee Surg Sports Traumatol Arthrosc. 2009;17:1289-1297.
47.
KogaHMunetaTNagaseT. Comparison of mesenchymal tissues-derived stem cells for in vivo chondrogenesis: suitable conditions for cell therapy of cartilage defects in rabbit. Cell Tissue Res. 2008;333:207-215.
48.
KogaHShimayaMMunetaT. Local adherent technique for transplanting mesenchymal stem cells as a potential treatment of cartilage defect. Arthritis Res Ther. 2008;10:R84.
49.
KurodaRIshidaKMatsumotoT. Treatment of a full thickness articular cartilage defect in the femoral condyle of an athlete with autologous bone marrow stromal cells. Osteoarthritis Cartilage. 2007;15:226-231.
50.
LahijiASohrabiAHungerfordDSFrondozaCG. Chitosan supports expression of extracellular matrix proteins in human osteoblasts and chondrocytes. J Biomed Mater Res. 2000;51:586-595.
51.
LeeCHSinglaALeeY. Biomedical applications of collagen. Int J Pharm. 2001;221:1-22.
52.
LeeEHHuiJH. The potential of stem cells in orthopaedic surgery. J Bone Joint Surg Br. 2006;88:841-851.
53.
LeeKBLHuiJHSongICArdanyLLeeEH. Injectable mesenchymal stem cell therapy for large cartilage defects: a porcine model. Stem Cells. 2007;25:2964-2971.
54.
LeeOKKuoTKChenWMLeeKDHseihSLChenTM. Isolation of multipotent mesenchymal stem cells from umbilical cord blood. Blood. 2004;103:1669-1675.
55.
LimJKHuiJLiL. Enhancement of tendon graft osteointegration using mesenchymal stem cells in a rabbit model of anterior cruciate ligament reconstruction. Arthroscopy. 2004;20:899-910.
56.
LokenSJakobsenRBAroenAThambyahAGohJLeeEH. Bone marrow mesenchymal stem cells in a hyaluron scaffold for treatment of an osteochondral defect in a rabbit model. Knee Surg Sports Traumatol Arthrosc. 2008;16:896-903.
57.
MakowerAMWroblewskiJPawlowskiA. Effects of IGF-I, rGH, FGF, EGF and NCS on DNA-synthesis, cell proliferation and morphology of chondrocytes isolated from rat rib growth cartilage. Cell Biol Int Rep. 1989;13:259-270.
58.
MartinJABuckwalterJA. Aging, articular cartilage chondrocyte senescence and osteoarthritis. Biogerontology. 2002;3:257-264.
59.
MastrogiacomoMCanceddaRQuartoR. Effect of different growth factors on the chondrogenic potential of human bone stromal cells. Osteoarthritis Cartilage. 2001;9(suppl A):S36-S40.
60.
NejadnikHHuiJFeng ChoongEPTaiBCLeeEH. Autologous bone marrow-derived mesenchymal stem cells versus autologous chondrocyte implantation: an observational cohort study. Am J Sports Med. 2010;38:1110-1116.
61.
NimuraAMunetaTKogaH. Increased proliferation of human synovial mesenchymal stem cells with autologous human serum: comparisons with bone marrow mesenchymal stem cells and with fetal bovine serum. Arthritis Rheum. 2008;58:501-510.
62.
ObradovicBMartinIPaderaRFTreppoSFreedLEVunjak-NovakovicG. Integration of engineered cartilage. J Orthop Res. 2001;19:1089-1097.
63.
OchiMUchioYKawasakiKWakitaniSIwasaJ. Transplantation of cartilage-like tissue made by tissue engineering in the treatment of cartilage defects of the knee. J Bone Joint Surg Br. 2002;84:571-584.
64.
OrnitzDMMariePJ. FGF signaling pathways in endochondral and intramembranous bone development and human genetic disease. Genes Dev. 2002;16:1446-1465.
65.
PascarellaACiattiRPascarellaF. Treatment of articular cartilage lesions of the knee joint using a modified AMIC technique. Knee Surg Sports Traumatol Arthrosc. 2010;18:509-513.
66.
PelttariKWinterASteckE. Premature induction of hypertrophy during in vitro chondrogenesis of human mesenchymal stem cells correlates with calcification and vascular invasion after ectopic transplantation in SCID mice. Arthritis Rheum. 2006;54:3254-3266.
67.
PetriglianoFMcAllisterDWuB. Tissue engineering for anterior cruciate ligament reconstruction: a review of current strategies. Arthroscopy. 2006;22:441-451.
68.
PittengerMFMackayAMBeckSC. Multilineage potential of adult human mesenchymal stem cells. Science. 1999;284:143-147.
69.
PonticielloMSSchinaglRMKadiyalaSBarryFP. Gelatin-based resorbable sponge as a carrier matrix for human mesenchymal stem cells in cartilage regeneration therapy. J Biomed Mater Res. 2000;52:246-255.
70.
RubioDGarcia-CastroJMartinMC. Spontaneous human adult stem cell transformation. Cancer Res. 2005;65:3035-3039.
71.
SakaguchiYSekiyaIYagishitaKIchinoseSShinomayaKMunetaT. Suspended cells from trabecular bone by collagenase digestion become virtually identical to mesenchymal stem cells obtained from bone marrow aspirates. Blood. 2004;104:2728-2735.
72.
SakaguchiYSekiyaIYagishitaKMunetaT. Comparison of human stem cells derived from various mesenchymal tissues: superiority of synovium as a cell source. Arthritis Rheum. 2005;52:2521-2529.
73.
SawKYAnzAMericanS. Articular cartilage regeneration with autologous peripheral blood progenitor cells and hyaluronic acid after arthroscopic subchondral drilling: a report of 5 cases with histology. Arthroscopy. 2011;27:493-506.
74.
SawKYHussinPLokeSC. Articular cartilage regeneration with autologous marrow aspirate and hyaluronic acid: an experimental study in a goat model. Arthroscopy. 2009;25:1391-1400.
75.
SolchagaLAYooJULundbergM. Hyaluronan-based polymers in the treatment of osteochondral defects. J Orthop Res. 2000;18:773-780.
76.
SongLTuanRS. Transdifferentiation potential of human mesenchymal stem cells derived from bone marrow. FASEB J. 2004;18:980-982.
77.
SoonMYHassanAHuiJH. An analysis of soft tissue allograft anterior cruciate ligament reconstruction in a rabbit model: a short-term study of the use of mesenchymal stem cells to enhance tendon osteointegration. Am J Sports Med. 2007;35:962-971.
SteckEBettramHAbelRChenBWinterARichterW. Induction of intervertebral disc-like cells from adult mesenchymal stem cells. Stem Cells. 2005;23:403-411.
80.
SteckEFischerJLorenzH. Mesenchymal stem cell differentiation in an experimental cartilage defect: restriction of hypertrophy to bone-close neocartilage. Stem Cells Dev. 2009;18:969-978.
81.
TateishiKAndoWHiguchiC. Comparison of human serum with fetal bovine serum for expansion and differentiation of human synovial MSC: potential feasibility for clinical application. Cell Transplant. 2008;17:549-557.
Van EjikFSarisDBRiesleJ. Tissue engineering of ligaments: a comparison of bone marrow stromal cells, anterior cruciate ligament, and skin fibroblasts as cell source. Tissue Eng. 2004;10:893-903.
84.
VinardellTThorpeSDBuckleyCTKellyDJ. Chondrogenesis and integration of mesenchymal stem cells within an in vitro cartilage defect repair model. Ann Biomed Eng. 2009;37:2556-2565.
85.
WakitaniSGotoTPinedaSJ. Mesenchymal cell-based repair of large, full-thickness defects of articular cartilage. J Bone Joint Surg Am. 1994;76:579-592.
86.
WakitaniSImotoKYamamotoTSaitoMMurataNYonedaM. Human autologous culture expanded bone marrow mesenchymal cell transplantation for repair of cartilage defects in osteoarthritic knees. Osteoarthritis Cartilage. 2002;10:199-206.
87.
WakitaniSMitsuokaTNakamuraNToritsukaYNakamuraYHoribeS. Autologous bone marrow stromal cell transplantation for repair of full thickness articular cartilage defects in human patellae: two case reports. Cell Transplant. 2004;13:595-600.
88.
WakitaniSNawataMTenshoKOkabeTMachidaHOhgushiH. Repair of articular cartilage defects in the patello-femoral joint with autologous bone marrow mesenchymal cell transplantation: three case reports involving nine defects in five knees. J Tissue Eng Regen Med. 2007;1:74-79.
89.
WickhamMQEricksonGRGimbleJMVailTPGuilakF. Multipotent stromal cells derived from the infrapatellar fat pad of the knee. Clin Orthop Relat Res. 2003;412:196-212.
90.
WozneyJM. The bone morphogenetic protein family: multifunctional cellular regulators in the embryo and adult. Eur J Oral Sci. 1998;106: 160-166.
91.
YangJWde IslaNHuselsteinC. Evaluation of human MSCs cell cycle, viability and differentiation in micromass culture. Biorheology. 2006;43:489-496.
92.
YokoyamaASekiyaIMiyazakiKIchinoseSHataYMunetaT. In vitro cartilage formation of composites of synovium-derived mesenchymal stem cells with collagen gel. Cell Tissue Res. 2005;332:289-298.
93.
YooJUBarthelTSNishumuraK. The chondrogenic potential of human bone-marrow-derived mesenchymal progenitor cells. J Bone Joint Surg Am. 1998;80:1745-1757.
94.
YoshimuraHMunetaTNimuraAYokoyamaAKogaHSekiyaI. Comparison of rat mesenchymal stem cells derived from bone marrow, synovium, periosteum, adipose tissue and muscle. Cell Tissue Res. 2007;327:449-462.
95.
ZhengHMartinJADuwayriYFalconGBuckwalterJA. Impact of aging on rat bone marrow-derived stem cell chondrogenesis. J Gerontol. 2007;62A:136-148.
96.
ZukPAZhuMAshjianP. Human adipose tissue is a source of multipotent stem cells. Mol Biol Cell. 2002;13:4279-4295.
