Skip to main content

Advertisement

SpringerLink
Log in

Comparative efficacy of stem cells and secretome in articular cartilage regeneration: a systematic review and meta-analysis

  • Review
  • Published:
Cell and Tissue Research Aims and scope Submit manuscript

Abstract

Articular cartilage defect remains the most challenging joint disease due to limited intrinsic healing capacity of the cartilage that most often progresses to osteoarthritis. In recent years, stem cell therapy has evolved as therapeutic strategies for articular cartilage regeneration. However, a number of studies have shown that therapeutic efficacy of stem cell transplantation is attributed to multiple secreted factors that modulate the surrounding milieu to evoke reparative processes. This systematic review and meta-analysis aim to evaluate and compare the therapeutic efficacy of stem cell and secretome in articular cartilage regeneration in animal models. We systematically searched the PubMed, CINAHL, Cochrane Library, Ovid Medline and Scopus databases until August 2017 using search terms related to stem cells, cartilage regeneration and animals. A random effect meta-analysis of the included studies was performed to assess the treatment effects on new cartilage formation on an absolute score of 0–100% scale. Subgroup analyses were also performed by sorting studies independently based on similar characteristics. The pooled analysis of 59 studies that utilized stem cells significantly improved new cartilage formation by 25.99% as compared with control. Similarly, the secretome also significantly increased cartilage regeneration by 26.08% in comparison to the control. Subgroup analyses revealed no significant difference in the effect of stem cells in new cartilage formation. However, there was a significant decline in the effect of stem cells in articular cartilage regeneration during long-term follow-up, suggesting that the duration of follow-up is a predictor of new cartilage formation. Secretome has shown a similar effect to stem cells in new cartilage formation. The risk of bias assessment showed poor reporting for most studies thereby limiting the actual risk of bias assessment. The present study suggests that both stem cells and secretome interventions improve cartilage regeneration in animal trials.

ᅟ

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5

Similar content being viewed by others

References

  • Akpancar S, Tatar O, Turgut H, Akyildiz F, Ekinci S (2016) The current perspectives of stem cell therapy in orthopedic surgery. Arch Trauma Res 5(4):e37976

    Article  PubMed  PubMed Central  Google Scholar 

  • Al Faqeh H, Nor Hamdan BMY, Chen HC, Aminuddin BS, Ruszymah BHI (2012) The potential of intra-articular injection of chondrogenic-induced bone marrow stem cells to retard the progression of osteoarthritis in a sheep model. Exp Gerontol 47:458–464

    Article  PubMed  Google Scholar 

  • Ando W, Tateishi K, Hart DA, Katakai D, Tanaka Y, Nakata K, Hashimoto J, Fujie H, Shino K, Yoshikawa H, Nakamura N (2007) Cartilage repair using an in vitro generated scaffold-free tissue-engineered construct derived from porcine synovial mesenchymal stem cells. Biomaterials 28:5462–5470

    Article  CAS  PubMed  Google Scholar 

  • Angele P, Johnstone B, Kujat R, Zellner J, Nerlich M, Goldberg V, Yoo J (2008) Stem cell based tissue engineering for meniscus repair. J Biomed Mater Res A 85:445–455

    Article  CAS  PubMed  Google Scholar 

  • Baraniak PR, McDevitt TC (2010) Stem cell paracrine actions and tissue regeneration. Regen Med 5:121–143

    Article  PubMed  Google Scholar 

  • Barron V, Merghani K, Shaw G, Coleman CM, Hayes JS, Ansboro S, Manian A, O’Malley G, Connolly E, Nandakumar A, van Blitterswijk CA, Habibovic P, Moroni L, Shannon F, Murphy JM, Barry F (2015) Evaluation of cartilage repair by mesenchymal stem cells seeded on a PEOT/PBT scaffold in an osteochondral defect. Ann Biomed Eng 43:2069–2082

    Article  CAS  PubMed  Google Scholar 

  • Begg CB, Mazumdar M (1994) Operating characteristics of a rank correlation test for publication bias. Biometrics 50:1088–1101

    Article  CAS  PubMed  Google Scholar 

  • Bentley G, Biant LC, Vijayan S, Macmull S, Skinner JA, Carrington RWJ (2012) Minimum ten-year results of a prospective randomised study of autologous chondrocyte implantation versus mosaicplasty for symptomatic articular cartilage lesions of the knee. J Bone Joint Surg (Br) 94:504–509

    Article  CAS  Google Scholar 

  • Bhandari M, Smith J, Miller LE, Block JE (2012) Clinical and economic burden of revision knee arthroplasty. Clin Med Insights Arthritis Musculoskelet Disord 5:89–94

    Article  PubMed  PubMed Central  Google Scholar 

  • Caldwell KL, Wang J (2015) Cell-based articular cartilage repair: the link between development and regeneration. Osteoarthr Cartil 23:351–362

    Article  CAS  Google Scholar 

  • Caminal M, Moll X, Codina D, Rabanal RM, Morist A, Barrachina J, Garcia F, Pla A, Vives J (2014) Transitory improvement of articular cartilage characteristics after implantation of polylactide:polyglycolic acid (PLGA) scaffolds seeded with autologous mesenchymal stromal cells in a sheep model of critical-sized chondral defect. Biotechnol Lett 38:2143–2153

    Article  CAS  Google Scholar 

  • Caminal M, Peris D, Fonseca C, Barrachina J, Codina D, Rabanal RM, Moll X, Morist A, García F, Cairó JJ, Gòdia F, Pla A, Vives J (2016) Cartilage resurfacing potential of PLGA scaffolds loaded with autologous cells from cartilage, fat, and bone marrow in an ovine model of osteochondral focal defect. Cytotechnology 68:907–919

    Article  CAS  PubMed  Google Scholar 

  • Ceylan HH, Bilsel K, Buyukpinarbasili N, Ceylan H, Erdil M, Tuncay I, Sen C (2016) Can chondral healing be improved following microfracture? The effect of adipocyte tissue derived stem cell therapy. Knee 23:442–449

    Article  PubMed  Google Scholar 

  • Chang CH, Kuo TF, Lin FH, Wang JH, Hsu YM, Huang HT, Loo ST, Fang HW, Liu HC, Wang WC (2011) Tissue engineering-based cartilage repair with mesenchymal stem cells in a porcine model. J Orthop Res 29:1874–1880

    Article  CAS  PubMed  Google Scholar 

  • Chang F, Ishii T, Yanai T, Mishima H, Akaogi H, Ogawa T, Ochiai N (2008) Repair of large full-thickness articular cartilage defects by transplantation of autologous uncultured bone-marrow-derived mononuclear cells. J Orthop Res 26:18–26

    Article  PubMed  Google Scholar 

  • Chiang ER, Ma HL, Wang JP, Liu CL, Chen TH, Hung SC (2016) Allogeneic mesenchymal stem cells in combination with hyaluronic acid for the treatment of osteoarthritis in rabbits. PLoS One 11:e0149835

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Chijimatsu R, Ikeya M, Yasui Y, Ikeda Y, Ebina K, Moriguchi Y, Shimomura K, Hart DA, Hideki Y, Norimasa N (2017) Characterization of mesenchymal stem cell-like cells derived from human iPSCs via neural crest development and their application for osteochondral repair. Stem Cells Int 2017:1960965

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Chung JY, Song M, Ha CW, Kim JA, Lee CH, Park YB (2014) Comparison of articular cartilage repair with different hydrogel-human umbilical cord blood-derived mesenchymal stem cell composites in a rat model. Stem Cell Res Ther 5:39. https://doi.org/10.1186/scrt427

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Dai L, He Z, Zhang X, Hu X, Yuan L, Qiang M, Zhu J, Shao Z, Zhou C, Ao Y (2014) One-step repair for cartilage defects in a rabbit model: a technique combining the perforated decalcified cortical-cancellous bone matrix scaffold with microfracture. Am J Sports Med 42:583–591

    Article  PubMed  Google Scholar 

  • Dai NT, Fan GY, Liou NH, Wang YW, Fu KY, Ma KH, Liu JC, Chang SC, Huang KL, Dai LG, Chen SG, Chen TM, Chen TM (2015) Histochemical and functional improvement of adipose-derived stem cell-based tissue-engineered cartilage by hyperbaric oxygen/air treatment in a rabbit articular defect model. Ann Plast Surg 74(Suppl 2):S139–S145

    Article  CAS  PubMed  Google Scholar 

  • Dashtdar H, Murali MR, Abbas AA, Suhaeb AM, Selvaratnam L, Tay LX, Kamarul T (2015) PVA-chitosan composite hydrogel versus alginate beads as a potential mesenchymal stem cell carrier for the treatment of focal cartilage defects. Knee Surg Sports Traumatol Arthrosc 23:1368–1377

    Article  PubMed  Google Scholar 

  • Dashtdar H, Rothan HA, Tay T, Ahmad RE, Ali R, Tay LX, Chong PP, Kamarul T (2011) A preliminary study comparing the use of allogenic chondrogenic pre-differentiated and undifferentiated mesenchymal stem cells for the repair of full thickness articular cartilage defects in rabbits. J Orthop Res 29:1336–1342

    Article  PubMed  Google Scholar 

  • Dattena M, Pilichi S, Rocca S, Mara L, Casu S, Masala G, Manunta A, Passino ES, Pool RR, Cappai P (2009) Sheep embryonic stem-like cells transplanted in full-thickness cartilage defects. J Tissue Eng Regen Med 3:175–187

    Article  CAS  PubMed  Google Scholar 

  • Davatchi F, Sadeghi Abdollahi B, Mohyeddin M, Nikbin B (2016) Mesenchymal stem cell therapy for knee osteoarthritis: 5 years follow-up of three patients. Int J Rheum Dis 19:219–225

    Article  PubMed  Google Scholar 

  • Delling U, Brehm W, Ludewig E, Winter K, Jülke H (2015) Longitudinal evaluation of effects of intra-articular mesenchymal stromal cell administration for the treatment of osteoarthritis in an ovine model. Cell Transplant 24:2391–2407

    Article  PubMed  Google Scholar 

  • Deng J, She R, Huang W, Dong Z, Mo G, Liu B (2013) A silk fibroin/chitosan scaffold in combination with bone marrow-derived mesenchymal stem cells to repair cartilage defects in the rabbit knee. J Mater Sci Mater Med 24:2037–2046

    Article  CAS  PubMed  Google Scholar 

  • Duan P, Pan Z, Cao L, He Y, Wang H, Qu Z, Dong J, Ding J (2014) The effects of pore size in bilayered poly(lactide-co-glycolide) scaffolds on restoring osteochondral defects in rabbits. J Biomed Mater Res A 102:180–192

    Article  CAS  PubMed  Google Scholar 

  • Egger M, Davey Smith G, Schneider M, Minder C (1997) Bias in meta-analysis detected by a simple, graphical test. BMJ 315:629–634

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Fekrazad R, Eslaminejad MB, Shayan AM, Kalhori KAM, Abbas FM, Taghiyar L, Sepehr Pedram M, Ghuchani M (2016) Effects of photobiomodulation and mesenchymal stem cells on articular cartilage defects in a rabbit model. Photomed Laser Surg 34:543–549

    Article  CAS  PubMed  Google Scholar 

  • Fisher MB, Belkin NS, Milby AH, Henning EA, Söegaard N, Kim M, Pfeifer C, Saxena V, Dodge GR, Burdick JA, Schaer TP, Steinberg DR, Mauck RL (2016) Effects of mesenchymal stem cell and growth factor delivery on cartilage repair in a mini-pig model. Cartilage 7:174–184

    Article  CAS  PubMed  Google Scholar 

  • Freitag J, Bates D, Boyd R, Shah K, Barnard A, Huguenin L, Tenen A (2016) Mesenchymal stem cell therapy in the treatment of osteoarthritis: reparative pathways, safety and efficacy—a review. BMC Musculoskelet Disord 17:230

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Fu WL, Zhou CY, Yu JK (2014) A new source of mesenchymal stem cells for articular cartilage repair: MSCs derived from mobilized peripheral blood share similar biological characteristics in vitro and chondrogenesis in vivo as MSCs from bone marrow in a rabbit model. Am J Sports Med 42:592–601

    Article  PubMed  Google Scholar 

  • Goldberg A, Mitchell K, Soans J, Kim L, Zaidi R (2017) The use of mesenchymal stem cells for cartilage repair and regeneration: a systematic review. J Orthop Surg 12:39

    Article  Google Scholar 

  • Goodrich LR, Chen AC, Werpy NM, Williams AA, Kisiday JD, Su AW, Cory E, Morley PS, McIlwraith CW, Sah RL, Chu CR (2016) Addition of mesenchymal stem cells to autologous platelet-enhanced fibrin scaffolds in chondral defects: does it enhance repair? J Bone Joint Surg Am 98:23–34

    Article  PubMed  PubMed Central  Google Scholar 

  • Guillén-García P, Rodríguez-Iñigo E, Guillén-Vicente I, Caballero-Santos R, Guillén-Vicente M, Abelow S, Giménez-Gallego G, López-Alcorocho JM (2014) Increasing the dose of autologous chondrocytes improves articular cartilage repair: histological and molecular study in the sheep animal model. Cartilage 5:114–122

    Article  PubMed  PubMed Central  Google Scholar 

  • Ha CW, Park YB, Chung JY, Park YG (2015) Cartilage repair using composites of human umbilical cord blood-derived mesenchymal stem cells and hyaluronic acid hydrogel in a minipig model. Stem Cells Transl Med 4:1044–1051

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Hatsushika D, Muneta T, Horie M, Koga H, Tsuji K, Sekiya I (2013) Intraarticular injection of synovial stem cells promotes meniscal regeneration in a rabbit massive meniscal defect model. J Orthop Res 31:1354–1359

    Article  CAS  PubMed  Google Scholar 

  • Hatsushika D, Muneta T, Nakamura T, Horie M, Koga H, Nakagawa Y, Tsuji K, Hishikawa S, Kobayashi E, Sekiya I (2014) Repetitive allogeneic intraarticular injections of synovial mesenchymal stem cells promote meniscus regeneration in a porcine massive meniscus defect model. Osteoarthr Cartil 22:941–950

    Article  CAS  Google Scholar 

  • Heijink A, Gomoll AH, Madry H, Drobnič M, Filardo G, Espregueira-Mendes J, Van Dijk CN (2012) Biomechanical considerations in the pathogenesis of osteoarthritis of the knee. Knee Surg Sports Traumatol Arthrosc 20:423–435

    Article  PubMed  Google Scholar 

  • Henderson VC, Kimmelman J, Fergusson D, Grimshaw JM, Hackam DG (2013) Threats to validity in the design and conduct of preclinical efficacy studies: a systematic review of guidelines for in vivo animal experiments. PLoS Med 10:e1001489

    Article  PubMed  PubMed Central  Google Scholar 

  • Hermeto LC, DeRossi R, Oliveira RJ, Pesarini JR, Antoniolli-Silva AC, Jardim PH, Santana AE, Deffune E, Rinaldi JC, Justulin LA (2016) Effects of intra-articular injection of mesenchymal stem cells associated with platelet-rich plasma in a rabbit model of osteoarthritis. Genet Mol Res 15(3). https://doi.org/10.4238/gmr.15038569

  • Hooijmans CR, Rovers MM, de Vries RB, Leenaars M, Ritskes-Hoitinga M, Langendam MW (2014) SYRCLE’s risk of bias tool for animal studies. BMC Med Res Methodol 14:43

    Article  PubMed  PubMed Central  Google Scholar 

  • Hopper N, Wardale J, Brooks R, Power J, Rushton N, Henson F (2015) Peripheral blood mononuclear cells enhance cartilage repair in in vivo osteochondral defect model. PLoS One 10:e0133937

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Horie M, Choi H, Lee RH, Reger RL, Ylostalo J, Muneta T, Sekiya I, Prockop DJ (2012a) Intra-articular injection of human mesenchymal stem cells (MSCs) promote rat meniscal regeneration by being activated to express Indian hedgehog that enhances expression of type II collagen. Osteoarthr Cartil 20:1197–1207

    Article  CAS  Google Scholar 

  • Horie M, Driscoll MD, Sampson HW, Sekiya I, Caroom CT, Prockop DJ, Thomas DB (2012b) Implantation of allogenic synovial stem cells promotes meniscal regeneration in a rabbit meniscal defect model. J Bone Joint Surg Am 94:701–712

    Article  PubMed  PubMed Central  Google Scholar 

  • Hu B, Ren JL, Zhang JR, Ma Q, Liu YP, Mao TQ (2010) Enhanced treatment of articular cartilage defect of the knee by intra-articular injection of Bcl-xL-engineered mesenchymal stem cells in rabbit model. J Tissue Eng Regen Med 4:105–114

    Article  CAS  PubMed  Google Scholar 

  • Hui JHP, Chen F, Thambyah A, Lee EH (2004) 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 Pediatr Orthop 24:427–433

    Article  PubMed  Google Scholar 

  • Hui TY, Cheung KMC, Cheung WL, Chan D, Chan BP (2008) In vitro chondrogenic differentiation of human mesenchymal stem cells in collagen microspheres: influence of cell seeding density and collagen concentration. Biomaterials 29:3201–3212

    Article  CAS  PubMed  Google Scholar 

  • Itokazu M, Wakitani S, Mera H, Tamamura Y, Sato Y, Takagi M, Nakamura H (2016) Transplantation of scaffold-free cartilage-like cell-sheets made from human bone marrow mesenchymal stem cells for cartilage repair: a preclinical study. Cartilage 7:361–372

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Jang KM, Lee JH, Park CM, Song HR, Wang JH (2014) Xenotransplantation of human mesenchymal stem cells for repair of osteochondral defects in rabbits using osteochondral biphasic composite constructs. Knee Surg Sports Traumatol Arthrosc 22:1434–1444

    Article  PubMed  Google Scholar 

  • Javanmard MZ, Asgari D, Karimipour M, Atabaki F, Farjah G, Niakani A (2015) Mesenchymal stem cells inhibit proteoglycan degeneration in a rat model of osteoarthritis. Gene Cell Tissue 2(4):e31011

    Google Scholar 

  • Jia S, Zhang T, Xiong Z, Pan W, Liu J, Sun W (2015) In vivo evaluation of a novel oriented scaffold-BMSC construct for enhancing full-thickness articular cartilage repair in a rabbit model. PLoS One 10:e0145667

    Article  PubMed  PubMed Central  Google Scholar 

  • Jiang L, Ma A, Song L, Hu Y, Dun H, Daloze P, Yu Y, Jiang J, Zafarullah M, Chen H (2014) Cartilage regeneration by selected chondrogenic clonal mesenchymal stem cells in the collagenase-induced monkey osteoarthritis model. J Tissue Eng Regen Med 8:896–905

    Article  CAS  PubMed  Google Scholar 

  • Jing X, Yang L, Duan X, Xie B, Chen W, Li Z, Tan H (2008) In vivo MR imaging tracking of magnetic iron oxide nanoparticle labeled, engineered, autologous bone marrow mesenchymal stem cells following intra-articular injection. Jt Bone Spine Rev Rhum 75:432–438

    Article  Google Scholar 

  • Jo CH, Lee YG, Shin WH, Kim H, Chai JW, Jeong EC, Kim JE, Shim H, Shin JS, Shin IS, Ra JC, Oh S, Yoon KS (2014) Intra-articular injection of mesenchymal stem cells for the treatment of osteoarthritis of the knee: a proof-of-concept clinical trial. Stem Cells 32:1254–1266

    Article  CAS  PubMed  Google Scholar 

  • Jung M, Kaszap B, Redöhl A, Steck E, Breusch S, Richter W, Gotterbarm T (2009) Enhanced early tissue regeneration after matrix-assisted autologous mesenchymal stem cell transplantation in full thickness chondral defects in a minipig model. Cell Transplant 18:923–932

    Article  PubMed  Google Scholar 

  • Kim JE, Lee SM, Kim SH, Tatman P, Gee AO, Kim DH, Lee KE, Jung Y, Kim SJ (2014) Effect of self-assembled peptide-mesenchymal stem cell complex on the progression of osteoarthritis in a rat model. Int J Nanomedicine 9(Suppl 1):141–157

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Ko JY, Kim KI, Park S, Im GI (2014) In vitro chondrogenesis and in vivo repair of osteochondral defect with human induced pluripotent stem cells. Biomaterials 35:3571–3581

    Article  CAS  PubMed  Google Scholar 

  • Ko JY, Lee J, Lee J, Im GI (2017) Intra-articular xenotransplantation of adipose-derived stromal cells to treat osteoarthritis in a goat model. Tissue Eng Regen Med 14:65–71. https://doi.org/10.1007/s13770-016-0010-5

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Koga H, Muneta T, Ju YJ, Nagase T, Nimura A, Mochizuki T, Ichinose S, von der Mark, Sekiya I (2007) Synovial stem cells are regionally specified according to local microenvironments after implantation for cartilage regeneration. Stem Cells 25:689–696

    Article  CAS  PubMed  Google Scholar 

  • Koga H, Shimaya M, Muneta T, Nimura A, Morito T, Hayashi M, Suzuki S, Ju YJ, Mochizuki T, Sekiya I (2008) Local adherent technique for transplanting mesenchymal stem cells as a potential treatment of cartilage defect. Arthritis Res Ther 10:R84. https://doi.org/10.1186/ar2460

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Kreuz PC, Müller S, Ossendorf C, Kaps C, Erggelet C (2009) Treatment of focal degenerative cartilage defects with polymer-based autologous chondrocyte grafts: four-year clinical results. Arthritis Res Ther 11:R33

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Lam J, Lu S, Lee EJ, Trachtenberg JE, Meretoja VV, Dahlin RL, van den Beucken JJ, Tabata Y, Wong ME, Jansen JA, Mikos AG, Kasper FK (2014) Osteochondral defect repair using bilayered hydrogels encapsulating both chondrogenically and osteogenically pre-differentiated mesenchymal stem cells in a rabbit model. Osteoarthr Cartil 22:1291–1300

    Article  CAS  Google Scholar 

  • Latief N, Raza FA, Bhatti FUR, Tarar MN, Khan SN, Riazuddin S (2016) Adipose stem cells differentiated chondrocytes regenerate damaged cartilage in rat model of osteoarthritis. Cell Biol Int 40:579–588

    Article  CAS  PubMed  Google Scholar 

  • Lee JC, Lee SY, Min HJ, Han SA, Jang J, Lee S, Seong SC, Lee MC (2012) Synovium-derived mesenchymal stem cells encapsulated in a novel injectable gel can repair osteochondral defects in a rabbit model. Tissue Eng A 18:2173–2186

    Article  CAS  Google Scholar 

  • Lee JC, Min HJ, Park HJ, Lee S, Seong SC, Lee MC (2013) Synovial membrane–derived mesenchymal stem cells supported by platelet-rich plasma can repair osteochondral defects in a rabbit model. Arthroscopy 29:1034–1046

    Article  PubMed  Google Scholar 

  • Lee KBL, Hui JHP, Song IC, Ardany L, Lee EH (2007) Injectable mesenchymal stem cell therapy for large cartilage defects—a porcine model. Stem Cells 25:2964–2971

    Article  PubMed  Google Scholar 

  • Leonard CA, Lee W-Y, Tailor P, Salo PT, Kubes P, Krawetz RJ (2015) Allogeneic bone marrow transplant from MRL/MpJ super-healer mice does not improve articular cartilage repair in the C57Bl/6 strain. PLoS One 10:e0131661

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Li WJ, Chiang H, Kuo TF, Lee HS, Jiang CC, Tuan RS (2009) Evaluation of articular cartilage repair using biodegradable nanofibrous scaffolds in a swine model: a pilot study. J Tissue Eng Regen Med 3:1–10

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Lin Z, Fitzgerald JB, Xu J, Willers C, Wood D, Grodzinsky AJ, Zheng MH (2008) Gene expression profiles of human chondrocytes during passaged monolayer cultivation. J Orthop Res 26:1230–1237

    Article  CAS  PubMed  Google Scholar 

  • Liu S, Jia Y, Yuan M, Guo W, Huang J, Zhao B, Peng J, Xu W, Lu S, Guo Q (2017) Repair of osteochondral defects using human umbilical cord Wharton’s jelly-derived mesenchymal stem cells in a rabbit model. Biomed Res Int 2017:8760383

    PubMed  PubMed Central  Google Scholar 

  • Løken S, Jakobsen RB, Arøen A, Heir S, Shahdadfar A, Brinchmann JE, Engebretsen L, Reinholt FP (2008) Bone marrow mesenchymal stem cells in a hyaluronan scaffold for treatment of an osteochondral defect in a rabbit model. Knee Surg Sports Traumatol Arthrosc 16:896–903

    Article  PubMed  Google Scholar 

  • Madrigal M, Rao KS, Riordan NH (2014) A review of therapeutic effects of mesenchymal stem cell secretions and induction of secretory modification by different culture methods. J Transl Med 12:260

    Article  PubMed  PubMed Central  Google Scholar 

  • Mahmoud EE, Kamei G, Harada Y, Shimizu R, Kamei N, Adachi N, Misk NA, Ochi M (2016) Cell magnetic targeting system for repair of severe chronic osteochondral defect in a rabbit model. Cell Transplant 25:1073–1083

    Article  PubMed  Google Scholar 

  • Mak J, Jablonski CL, Leonard CA, Dunn JF, Raharjo E, Matyas JR, Biernaskie J, Krawetz RJ (2016) Intra-articular injection of synovial mesenchymal stem cells improves cartilage repair in a mouse injury model. Sci Rep 6:23076

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Masuoka K, Asazuma T, Hattori H, Yoshihara Y, Sato M, Matsumura K, Matsui T, Takase B, Nemoto K, Ishihara M (2006) Tissue engineering of articular cartilage with autologous cultured adipose tissue-derived stromal cells using atelocollagen honeycomb-shaped scaffold with a membrane sealing in rabbits. J Biomed Mater Res B Appl Biomater 79:25–34

    Article  CAS  PubMed  Google Scholar 

  • Mata M, Milian L, Oliver M, Zurriaga J, Sancho-Tello M, de Llano JJM, Carda C (2017) In vivo articular cartilage regeneration using human dental pulp stem cells cultured in an alginate scaffold: a preliminary study. Stem Cells Int 2017:8309256

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Matsumoto T, Cooper GM, Gharaibeh B, Meszaros LB, Li G, Usas A, Fu FH, Huard J (2009) Cartilage repair in a rat model of osteoarthritis through intraarticular transplantation of muscle-derived stem cells expressing bone morphogenetic protein 4 and soluble Flt-1. Arthritis Rheum 60:1390–1405

    Article  PubMed  PubMed Central  Google Scholar 

  • Maumus M, Roussignol G, Toupet K, Penarier G, Bentz I, Teixeira S, Oustric D, Jung M, Lepage O, Steinberg R, Jorgensen C, Noel D (2016) Utility of a mouse model of osteoarthritis to demonstrate cartilage protection by IFNγ-primed equine mesenchymal stem cells. Front Immunol 7:392

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • McCarty RC, Xian CJ, Gronthos S, Zannettino AC, Foster BK (2010) Application of autologous bone marrow derived mesenchymal stem cells to an ovine model of growth plate cartilage injury. Open Orthop J 4:204–210

    Article  PubMed  PubMed Central  Google Scholar 

  • McIlwraith CW, Frisbie DD, Rodkey WG, Kisiday JD, Werpy NM, Kawcak CE, Steadman JR (2011) Evaluation of intra-articular mesenchymal stem cells to augment healing of microfractured chondral defects. Arthroscopy 27:1552–1561

    Article  PubMed  Google Scholar 

  • Mehrabani D, Babazadeh M, Tanideh N, Zare S, Hoseinzadeh S, Torabinejad S, Koohi-Hosseinabadi O (2015) The healing effect of adipose-derived mesenchymal stem cells in full-thickness femoral articular cartilage defects of rabbit. Int J Organ Transplant Med 6:165–175

    CAS  PubMed  PubMed Central  Google Scholar 

  • Mei L, Shen B, Ling P, Liu S, Xue J, Liu F, Shao H, Chen J, Ma A, Liu X (2017) Culture-expanded allogenic adipose tissue-derived stem cells attenuate cartilage degeneration in an experimental rat osteoarthritis model. PLoS One 12:e0176107

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Meirelles L d S, Fontes AM, Covas DT, Caplan AI (2009) Mechanisms involved in the therapeutic properties of mesenchymal stem cells. Cytokine Growth Factor Rev 20:419–427

    Article  CAS  Google Scholar 

  • Mifune Y, Matsumoto T, Murasawa S, Kawamoto A, Kuroda R, Shoji T, Kuroda T, Fukui T, Kawakami Y, Kurosaka M, Asahara T (2013) Therapeutic superiority for cartilage repair by CD271-positive marrow stromal cell transplantation. Cell Transplant 22:1201–1211

    Article  PubMed  Google Scholar 

  • Miller RE, Grodzinsky AJ, Vanderploeg EJ, Lee C, Ferris DJ, Barrett MF, Kisiday JD, Frisbie DD (2010) Effect of self-assembling peptide, chondrogenic factors, and bone marrow derived stromal cells on osteochondral repair. Osteoarthr Cartil 18:1608–1619

    Article  CAS  Google Scholar 

  • Mobasheri A, Csaki C, Clutterbuck AL, Rahmanzadeh M, Shakibaei M (2009) Mesenchymal stem cells in connective tissue engineering and regenerative medicine: applications in cartilage repair and osteoarthritis therapy. Histol Histopathol 24:347–366

    CAS  PubMed  Google Scholar 

  • Moher D, Liberati A, Tetzlaff J, Altman DG, Group TP (2009) Preferred reporting items for systematic reviews and meta-analyses: the PRISMA statement. PLoS Med 6:e1000097

    Article  PubMed  PubMed Central  Google Scholar 

  • Mokbel A, El-Tookhy O, Shamaa AA, Sabry D, Rashed L, Mostafa A (2011a) Homing and efficacy of intra-articular injection of autologous mesenchymal stem cells in experimental chondral defects in dogs. Clin Exp Rheumatol 29:275–284

    CAS  PubMed  Google Scholar 

  • Mokbel AN, El Tookhy OS, Shamaa AA, Rashed LA, Sabry D, El Sayed AM (2011b) Homing and reparative effect of intra-articular injection of autologus mesenchymal stem cells in osteoarthritic animal model. BMC Musculoskelet Disord 12:259

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Moran CJ, Ramesh A, Brama PAJ, O’Byrne JM, O’Byrne FJ, Levingstone TJ (2016) The benefits and limitations of animal models for translational research in cartilage repair. J Exp Orthop 3:1

    Article  PubMed  PubMed Central  Google Scholar 

  • Mrugala D, Bony C, Neves N, Caillot L, Fabre S, Moukoko D, Jorgensen C, Noël D (2008) Phenotypic and functional characterisation of ovine mesenchymal stem cells: application to a cartilage defect model. Ann Rheum Dis 67:288–295

    Article  CAS  PubMed  Google Scholar 

  • Muhammad SA, Nordin N, Fakurazi S (2018) Regenerative potential of secretome from dental stem cells: a systematic review of preclinical studies. Rev Neurosci 29:321–332

    Article  PubMed  Google Scholar 

  • Murdoch AD, Grady LM, Ablett MP, Katopodi T, Meadows RS, Hardingham TE (2007) Chondrogenic differentiation of human bone marrow stem cells in transwell cultures: generation of scaffold-free cartilage. Stem Cells 25:2786–2796

    Article  CAS  PubMed  Google Scholar 

  • Murphy JM, Fink DJ, Hunziker EB, Barry FP (2003) Stem cell therapy in a caprine model of osteoarthritis. Arthritis Rheum 48:3464–3474

    Article  PubMed  Google Scholar 

  • Nakagawa Y, Muneta T, Kondo S, Mizuno M, Takakuda K, Ichinose S, Tabuchi T, Koga H, Tsuji K, Sekiya I (2015) Synovial mesenchymal stem cells promote healing after meniscal repair in microminipigs. Osteoarthr Cartil 23:1007–1017

    Article  CAS  Google Scholar 

  • Nakagawa Y, Muneta T, Otabe K, Ozeki N, Mizuno M, Udo M, Saito R, Yanagisawa K, Ichinose S, Koga H, Tsuji K, Sekiya I (2016) Cartilage derived from bone marrow mesenchymal stem cells expresses lubricin in vitro and in vivo. PLoS One 11(2):e0148777

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Nakamura T, Sekiya I, Muneta T, Hatsushika D, Horie M, Tsuji K, Kawarasaki T, Watanabe A, Hishikawa S, Fujimoto Y, Tanaka H, Kobayashi E (2012) Arthroscopic, histological and MRI analyses of cartilage repair after a minimally invasive method of transplantation of allogeneic synovial mesenchymal stromal cells into cartilage defects in pigs. Cytotherapy 14:327–338

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Nam HY, Karunanithi P, Loo WC, Naveen S, Chen H, Hussin P, Chan L, Kamarul T (2013) The effects of staged intra-articular injection of cultured autologous mesenchymal stromal cells on the repair of damaged cartilage: a pilot study in caprine model. Arthritis Res Ther 15:R129

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Necas A, Plánka L, Srnec R, Crha M, Hlucilová J, Klíma J, Starý D, Kren L, Amler E, Vojtová L, Jancár J, Gál P (2010) Quality of newly formed cartilaginous tissue in defects of articular surface after transplantation of mesenchymal stem cells in a composite scaffold based on collagen I with chitosan micro- and nanofibres. Physiol Res 59:605–614

    CAS  PubMed  Google Scholar 

  • Nejadnik H, Lenkov O, Gassert F, Fretwell D, Lam I, Daldrup-Link HE (2016) Macrophage phagocytosis alters the MRI signal of ferumoxytol-labeled mesenchymal stromal cells in cartilage defects. Sci Rep 6:25897

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Nishimori M, Deie M, Kanaya A, Exham H, Adachi N, Ochi M (2006) Repair of chronic osteochondral defects in the rat. A bone marrow-stimulating procedure enhanced by cultured allogenic bone marrow mesenchymal stromal cells. J Bone Joint Surg (Br) 88:1236–1244

    Article  CAS  Google Scholar 

  • Oshima Y, Watanabe N, Matsuda K, Takai S, Kawata M, Kubo T (2004) Fate of transplanted bone-marrow-derived mesenchymal cells during osteochondral repair using transgenic rats to simulate autologous transplantation. Osteoarthr Cartil 12:811–817

    Article  Google Scholar 

  • Oshima Y, Watanabe N, Matsuda K, Takai S, Kawata M, Kubo T (2005) Behavior of transplanted bone marrow-derived GFP mesenchymal cells in osteochondral defect as a simulation of autologous transplantation. J Histochem Cytochem 53:207–216

    Article  CAS  PubMed  Google Scholar 

  • Ozeki N, Muneta T, Matsuta S, Koga H, Nakagawa Y, Mizuno M, Tsuji K, Mabuchi Y, Akazawa C, Kobayashi E, Matsumoto K, Futamura K, Saito T, Sekiya I (2015) Synovial mesenchymal stem cells promote meniscus regeneration augmented by an autologous Achilles tendon graft in a rat partial meniscus defect model. Stem Cells 33:1927–1938

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Panagiotou N, Wayne Davies R, Selman C, Shiels PG (2016) Microvesicles as vehicles for tissue regeneration: changing of the guards. Curr Pathobiol Rep 4:181–187

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Park JS, Woo DG, Yang HN, Lim HJ, Park KM, Na K, Park KH (2010) Chondrogenesis of human mesenchymal stem cells encapsulated in a hydrogel construct: neocartilage formation in animal models as both mice and rabbits. J Biomed Mater Res A 92:988–996

    PubMed  Google Scholar 

  • Park YB, Ha CW, Kim JA, Han WJ, Rhim JH, Lee HJ, Kim KJ, Park YG, Chung JY (2017) Single-stage cell-based cartilage repair in a rabbit model: cell tracking and in vivo chondrogenesis of human umbilical cord blood-derived mesenchymal stem cells and hyaluronic acid hydrogel composite. Osteoarthr Cartil 25:570–580

    Article  CAS  Google Scholar 

  • Park YB, Ha CW, Kim JA, Rhim JH, Park YG, Chung JY, Lee HJ (2016) Effect of transplanting various concentrations of a composite of human umbilical cord blood-derived mesenchymal stem cells and hyaluronic acid hydrogel on articular cartilage repair in a rabbit model. PLoS One 11:e0165446

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Park YB, Song M, Lee CH, Kim JA, Ha CW (2015) Cartilage repair by human umbilical cord blood-derived mesenchymal stem cells with different hydrogels in a rat model. J Orthop Res 33:1580–1586

    Article  CAS  PubMed  Google Scholar 

  • Parrilli A, Giavaresi G, Ferrari A, Salamanna F, Desando G, Grigolo B, Martini L, Fini M (2017) Subchondral bone response to injected adipose-derived stromal cells for treating osteoarthritis using an experimental rabbit model. Biotech Histochem 92:201–211

    Article  CAS  PubMed  Google Scholar 

  • Pas HI, Winters M, Haisma HJ, Koenis MJ, Tol JL, Moen MH (2017) Stem cell injections in knee osteoarthritis: a systematic review of the literature. Br J Sports Med 51:1125–1133

    Article  PubMed  Google Scholar 

  • Pei M, He F, Li J, Tidwell JE, Jones AC, McDonough EB (2013) Repair of large animal partial-thickness cartilage defects through intraarticular injection of matrix-rejuvenated synovium-derived stem cells. Tissue Eng A 19:1144–1154

    Article  CAS  Google Scholar 

  • Pescador D, Ibáñez-Fonseca A, Sánchez-Guijo F, Briñón JG, Arias FJ, Muntión S, Hernández C, Girotti A, Alonso M, Del Cañizo MC, Rodríguez-Cabello JC, Blanco JF (2017) Regeneration of hyaline cartilage promoted by xenogeneic mesenchymal stromal cells embedded within elastin-like recombinamer-based bioactive hydrogels. J Mater Sci Mater Med 28:115

    Article  CAS  PubMed  Google Scholar 

  • Petchdee S, Suphamungm W, Bootcha R (2016) Therapeutic benefit of intra-articular administration of deciduous teeth stem cells in rabbit model of osteoarthritis. Asian J Anim Vet Adv 11:363–370

    Article  CAS  Google Scholar 

  • Pilichi S, Rocca S, Pool RR, Dattena M, Masala G, Mara L, Sanna D, Casu S, Manunta ML, Manunta A, Passino ES (2014) Treatment with embryonic stem-like cells into osteochondral defects in sheep femoral condyles. BMC Vet Res 10:301

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Platas J, Guillén MI, del Caz MDP, Gomar F, Mirabet V, Alcaraz MJ (2013) Conditioned media from adipose-tissue-derived mesenchymal stem cells downregulate degradative mediators induced by interleukin-1β in osteoarthritic chondrocytes. Mediat Inflamm 2013:357014

    Article  CAS  Google Scholar 

  • Pot MW, Gonzales VK, Buma P, IntHout J, van Kuppevelt TH, de Vries RBM, Daamen WF et al (2016) Improved cartilage regeneration by implantation of acellular biomaterials after bone marrow stimulation: a systematic review and meta-analysis of animal studies. PeerJ 4:e2243

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Proffen BL, Vavken P, Haslauer CM, Fleming BC, Harris CE, Machan JT, Murray MM (2015) Addition of autologous mesenchymal stem cells to whole blood for bioenhanced ACL repair has no benefit in the porcine model. Am J Sports Med 43:320–330. https://doi.org/10.1177/0363546514559826

    Article  PubMed  Google Scholar 

  • Qi B, Yu A, Zhu S, Zhou M, Wu G (2013) Chitosan/poly(vinyl alcohol) hydrogel combined with Ad-hTGF-β1 transfected mesenchymal stem cells to repair rabbit articular cartilage defects. Exp Biol Med Maywood NJ 238:23–30

    Article  CAS  Google Scholar 

  • Qi Y, Yang Z, Ding Q, Zhao T, Huang Z, Feng G (2016) Targeted transplantation of iron oxide-labeled, adipose-derived mesenchymal stem cells in promoting meniscus regeneration following a rabbit massive meniscal defect. Exp Ther Med 11:458–466

    Article  CAS  PubMed  Google Scholar 

  • Qi Y, Zhao T, Xu K, Dai T, Yan W (2012) The restoration of full-thickness cartilage defects with mesenchymal stem cells (MSCs) loaded and cross-linked bilayer collagen scaffolds on rabbit model. Mol Biol Rep 39:1231–1237

    Article  CAS  PubMed  Google Scholar 

  • Rai V, Dilisio MF, Dietz NE, Agrawal DK (2017) Recent strategies in cartilage repair: a systemic review of the scaffold development and tissue engineering. J Biomed Mater Res A 105:2343–2354

    Article  CAS  PubMed  Google Scholar 

  • Ruiz-Ibán MÁ, Díaz-Heredia J, García-Gómez I, Gonzalez-Lizán F, Elías-Martín E, Abraira V (2011) The effect of the addition of adipose-derived mesenchymal stem cells to a meniscal repair in the avascular zone: an experimental study in rabbits. Arthroscopy 27:1688–1696

    Article  PubMed  Google Scholar 

  • Sato M, Uchida K, Nakajima H, Miyazaki T, Guerrero AR, Watanabe S, Roberts S, Baba H (2012) Direct transplantation of mesenchymal stem cells into the knee joints of Hartley strain guinea pigs with spontaneous osteoarthritis. Arthritis Res Ther 14:R31

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Saulnier N, Viguier E, Perrier-Groult E, Chenu C, Pillet E, Roger T, Maddens S, Boulocher C (2015) Intra-articular administration of xenogeneic neonatal mesenchymal stromal cells early after meniscal injury down-regulates metalloproteinase gene expression in synovium and prevents cartilage degradation in a rabbit model of osteoarthritis. Osteoarthr Cartil 23:122–133

    Article  CAS  Google Scholar 

  • Schelbergen RF, van Dalen S, ter Huurne M, Roth J, Vogl T, Noël D, Jorgensen C, van den Berg WB, van de Loo FA, Blom AB, van Lent PLEM (2014) Treatment efficacy of adipose-derived stem cells in experimental osteoarthritis is driven by high synovial activation and reflected by S100A8/A9 serum levels. Osteoarthr Cartil 22:1158–1166

    Article  CAS  Google Scholar 

  • Shi J, Zhang X, Zhu J, Pi Y, Hu X, Zhou C, Ao Y (2013) Nanoparticle delivery of the bone morphogenetic protein 4 gene to adipose-derived stem cells promotes articular cartilage repair in vitro and in vivo. Arthroscopy 29:2001–2011

    Article  PubMed  Google Scholar 

  • Shim G, Lee S, Han J, Kim G, Jin H, Miao W, Yi TG, Cho YK, Song SU, Oh YK (2014) Pharmacokinetics and in vivo fate of intra-articularly transplanted human bone marrow-derived clonal mesenchymal stem cells. Stem Cells Dev 24:1124–1132

    Article  CAS  Google Scholar 

  • Shim J-H, Jang K-M, Hahn SK, Park JY, Jung H, Oh K, Park KM, Yeom J, Park SH, Kim SW, Wang JH, Kim K, Cho DW (2016) Three-dimensional bioprinting of multilayered constructs containing human mesenchymal stromal cells for osteochondral tissue regeneration in the rabbit knee joint. Biofabrication 8:014102

    Article  CAS  PubMed  Google Scholar 

  • Shimomura K, Ando W, Tateishi K, Nansai R, Fujie H, Hart DA, Gobbi A, Kita K, Horibe S, Shino K, Yoshikawa H, Nakamura N (2010) The influence of skeletal maturity on allogenic synovial mesenchymal stem cell-based repair of cartilage in a large animal model. Biomaterials 31:8004–8011

    Article  CAS  PubMed  Google Scholar 

  • Singh A, Goel SC, Gupta KK, Kumar M, Arun GR, Patil H, Kumaraswamy V, Jha S (2014) The role of stem cells in osteoarthritis: an experimental study in rabbits. Bone Joint Res 3:32–37

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Song F, Tang J, Geng R, Hu H, Zhu C, Cui W, Fan W (2014) Comparison of the efficacy of bone marrow mononuclear cells and bone mesenchymal stem cells in the treatment of osteoarthritis in a sheep model. Int J Clin Exp Pathol 7:1415–1426

    PubMed  PubMed Central  Google Scholar 

  • Sridharan B, Laflin AD, Holtz MA, Pacicca DM, Wischmeier NK, Detamore MS (2017) In vivo evaluation of stem cell aggregates on osteochondral regeneration. J Orthop Res 35:1606–1616

    Article  CAS  PubMed  Google Scholar 

  • Sterne JAC, Sutton AJ, Ioannidis JPA, Terrin N, Jones DR, Lau J, Carpenter J, Rücker G, Harbord RM, Schmid CH, Tetzlaff J, Deeks JJ, Peters J, Macaskill P, Schwarzer G, Duval S, Altman DG, Moher D, Higgins JP (2011) Recommendations for examining and interpreting funnel plot asymmetry in meta-analyses of randomised controlled trials. BMJ 343:d4002

    Article  PubMed  Google Scholar 

  • Suhaeb AM, Naveen S, Mansor A, Kamarul T (2012) Hyaluronic acid with or without bone marrow derived-mesenchymal stem cells improves osteoarthritic knee changes in rat model: a preliminary report. Indian J Exp Biol 50:383–390

    CAS  PubMed  Google Scholar 

  • Sun J, Hou X-K, Li X, Tang TT, Zhang RM, Kuang Y, Shi M (2009) Mosaicplasty associated with gene enhanced tissue engineering for the treatment of acute osteochondral defects in a goat model. Arch Orthop Trauma Surg 129:757–771

    Article  PubMed  Google Scholar 

  • Tao SC, Yuan T, Zhang YL, Yin WJ, Guo SC, Zhang CQ (2017) Exosomes derived from miR-140-5p-overexpressing human synovial mesenchymal stem cells enhance cartilage tissue regeneration and prevent osteoarthritis of the knee in a rat model. Theranostics 7:180–195

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Tay LX, Ahmad RE, Dashtdar H, Tay KW, Masjuddi T, Ab-Rahim S, Chong PP, Selvaratnam L, Kamarul T (2012) Treatment outcomes of alginate-embedded allogenic mesenchymal stem cells versus autologous chondrocytes for the repair of focal articular cartilage defects in a rabbit model. Am J Sports Med 40:83–90

    Article  PubMed  Google Scholar 

  • ter Huurne M, Schelbergen R, Blattes R, Blom A, de Munter W, Grevers LC, Jeanson J, Noël D, Casteilla L, Jorgensen C, van den Berg W, van Lent PLEM (2012) Antiinflammatory and chondroprotective effects of intraarticular injection of adipose-derived stem cells in experimental osteoarthritis. Arthritis Rheum 64:3604–3613

    Article  CAS  PubMed  Google Scholar 

  • Toghraie F, Razmkhah M, Gholipour MA, Faghih Z, Chenari N, Torabi Nezhad S, Nazhvani Dehghani S, Ghaderi A (2012) Scaffold-free adipose-derived stem cells (ASCs) improve experimentally induced osteoarthritis in rabbits. Arch Iran Med 15:495–499

    PubMed  Google Scholar 

  • Toghraie FS, Chenari N, Gholipour MA, Faghih Z, Torabinejad S, Dehghani S, Ghaderi A (2011) Treatment of osteoarthritis with infrapatellar fat pad derived mesenchymal stem cells in rabbit. Knee 18:71–75

    Article  CAS  PubMed  Google Scholar 

  • Toh WS, Lai RC, Hui JHP, Lim SK (2017) MSC exosome as a cell-free MSC therapy for cartilage regeneration: implications for osteoarthritis treatment. Semin Cell Dev Biol 67:56–64

    Article  CAS  PubMed  Google Scholar 

  • Toratani T, Nakase J, Numata H, Oshima T, Takata Y, Nakayama K, Tsuchiya H (2017) Scaffold-free tissue-engineered allogenic adipose-derived stem cells promote meniscus healing. Arthroscopy 33:346–354

    Article  PubMed  Google Scholar 

  • Ude CC, Ng MH, Chen CH, Htwe O, Amaramalar NS, Hassan S, Djordjevic I, Rani RA, Ahmad J, Yahya NM, Saim AB, Idrus RBH (2015) Improved functional assessment of osteoarthritic knee joint after chondrogenically induced cell treatment. Osteoarthr Cartil 23:1294–1306

    Article  CAS  Google Scholar 

  • Ude CC, Sulaiman SB, Min-Hwei N, Hui-Cheng C, Ahmad J, Yahaya NM, Saim AB, Idrus RBH (2014) Cartilage regeneration by chondrogenic induced adult stem cells in osteoarthritic sheep model. PLoS One 9:e98770

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Ullah I, Subbarao RB, Rho GJ (2015) Human mesenchymal stem cells—current trends and future prospective. Biosci Rep 35:1–18

    Article  CAS  Google Scholar 

  • Uto S, Nishizawa S, Takasawa Y, Asawa Y, Fujihara Y, Takato T, Hoshi K (2013) Bone and cartilage repair by transplantation of induced pluripotent stem cells in murine joint defect model. Biomed Res 34:281–288

    Article  CAS  PubMed  Google Scholar 

  • van Buul GM, Siebelt M, Leijs MJC, Bos PK, Waarsing JH, Kops N, Weinans H, Verhaar JA, Bernsen MR, van Osch GJVM (2014) Mesenchymal stem cells reduce pain but not degenerative changes in a mono-iodoacetate rat model of osteoarthritis. J Orthop Res 32:1167–1174

    Article  CAS  PubMed  Google Scholar 

  • Van Pham P, Bui KH-T, Ngo DQ, Vu NB, Truong NH, Phan NLC, Le DM, Duong TD, Nguyen TD, Le VT, Phan NK (2013) Activated platelet-rich plasma improves adipose-derived stem cell transplantation efficiency in injured articular cartilage. Stem Cell Res Ther 4:91

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Vishnubhatla I, Corteling R, Stevanato L, Hicks C, Sinden J (2014) The development of stem cell-derived exosomes as a cell-free regenerative medicine. J Circ Biomark 3:2

    Article  CAS  Google Scholar 

  • Wakayama H, Hashimoto N, Matsushita Y, Matsubara K, Yamamoto N, Hasegawa Y, Ueda M, Yamamoto A (2015) Factors secreted from dental pulp stem cells show multifaceted benefits for treating acute lung injury in mice. Cytotherapy 17:1119–1129

    Article  CAS  PubMed  Google Scholar 

  • Wakitani S, Yamamoto T (2002) Response of the donor and recipient cells in mesenchymal cell transplantation to cartilage defect. Microsc Res Tech 58:14–18

    Article  PubMed  Google Scholar 

  • Wakitani S, Aoki H, Harada Y, Sonobe M, Morita Y, Mu Y, Tomita N, Nakamura Y, Takeda S, Watanabe TK, Tanigami A (2004) Embryonic stem cells form articular cartilage, not teratomas, in osteochondral defects of rat joints. Cell Transplant 13:331–336

    Article  PubMed  Google Scholar 

  • Wang W, He N, Feng C, Liu V, Zhang L, Wang F, He J, Zhu T, Wang S, Qiao W, Li S, Zhou G, Zhang L, Dai C, Cao W (2015) Human adipose-derived mesenchymal progenitor cells engraft into rabbit articular cartilage. Int J Mol Sci 16:12076–12091

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Wang Y, Yu D, Liu Z, Zhou F, Dai J, Wu B, Zhou J, Heng BC, Zou XH, Ouyang H, Liu H (2017) Exosomes from embryonic mesenchymal stem cells alleviate osteoarthritis through balancing synthesis and degradation of cartilage extracellular matrix. Stem Cell Res Ther 8:189

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Wang ZJ, An RZ, Zhao JY, Zhang Q, Yang J, Wang JB, Wen GY, Yuan XH, Qi XW, Li SJ, Ye XC (2014) Repair of articular cartilage defects by tissue-engineered cartilage constructed with adipose-derived stem cells and acellular cartilaginous matrix in rabbits. Genet Mol Res 13:4599–4606

    Article  CAS  PubMed  Google Scholar 

  • Wehling P, Moser C, Maixner W (2016) How does surgery compare with advanced intra-articular therapies in knee osteoarthritis: current thoughts. Ther Adv Musculoskelet Dis 8:72–85

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Wilke MM, Nydam DV, Nixon AJ (2007) Enhanced early chondrogenesis in articular defects following arthroscopic mesenchymal stem cell implantation in an equine model. J Orthop Res 25:913–925

    Article  CAS  PubMed  Google Scholar 

  • Wolfstadt JI, Cole BJ, Ogilvie-Harris DJ, Viswanathan S, Chahal J (2015) Current concepts: the role of mesenchymal stem cells in the management of knee osteoarthritis. Sports Health 7:38–44

    Article  PubMed  PubMed Central  Google Scholar 

  • Xia Q, Zhu S, Wu Y, Wang J, Cai Y, Chen P, Li J, Heng BC, Ouyang HW, Lu P (2015) Intra-articular transplantation of atsttrin-transduced mesenchymal stem cells ameliorate osteoarthritis development. Stem Cells Transl Med 4:523–531

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Xu X, Shi D, Liu Y, Shen Y, Xu Z, Dai J, Chen D, Teng H, Jiang Q (2016) Synovium-derived mesenchymal stem cell sheet enhance autologous osteochondral transplantation in a rabbit model. Int J Clin Exp Med 9:10322–10332

    CAS  Google Scholar 

  • Xu X, Shi D, Liu Y, Yao Y, Dai J, XU Z, Chen D, Teng H, Jiang Q (2017) In vivo repair of full-thickness cartilage defect with human iPSC-derived mesenchymal progenitor cells in a rabbit model. Exp Ther Med 14:239–245

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Yamagata M, Yamamoto A, Kako E, Kaneko N, Matsubara K, Sakai K, Sawamoto K, Ueda M (2013) Human dental pulp-derived stem cells protect against hypoxic-ischemic brain injury in neonatal mice. Stroke 44:551–554

    Article  PubMed  Google Scholar 

  • Yamaguchi S, Aoyama T, Ito A, Nagai M, Iijima H, Tajino J, Zhang X, Kiyan W, Kuroki H (2016) The effect of exercise on the early stages of mesenchymal stromal cell-induced cartilage repair in a rat osteochondral defect model. PLoS One 11:e0151580

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Yan H, Yu C (2007) Repair of full-thickness cartilage defects with cells of different origin in a rabbit model. Arthroscopy 23:178–187

    Article  PubMed  Google Scholar 

  • Yang D, Wang W, Li L, Peng Y, Chen P, Huang H, Guo Y, Xia X, Wang Y, Wang H, Wang WE, Zeng C (2013) The relative contribution of paracine effect versus direct differentiation on adipose-derived stem cell transplantation mediated cardiac repair. PLoS One 8:e59020

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Yang X, Zhu TY, Wen LC, Cao YP, Liu C, Cui YP, Liu C, Cui YP, Meng ZC, Liu H (2015) Intraarticular injection of allogenic mesenchymal stem cells has a protective role for the osteoarthritis. Chin Med J 128:2516–2523

    Article  PubMed  PubMed Central  Google Scholar 

  • Yun S, Ku SK, Kwon YS (2016) Adipose-derived mesenchymal stem cells and platelet-rich plasma synergistically ameliorate the surgical-induced osteoarthritis in Beagle dogs. J Orthop Surg 11:9

    Article  Google Scholar 

  • Zellner J, Hierl K, Mueller M, Pfeifer C, Berner A, Dienstknecht T, Krutsch W, Geis S, Gehmert S, Kujat R, Dendorfer S, Prantl L, Nerlich M, Angele P (2013) Stem cell-based tissue-engineering for treatment of meniscal tears in the avascular zone. J Biomed Mater Res B Appl Biomater 101:1133–1142

    Article  CAS  PubMed  Google Scholar 

  • Zellner J, Taeger CD, Schaffer M, Roldan JC, Loibl M, Mueller MB, Berner A, Krutsch W, Huber MK, Kujat R, Nerlich M, Angele P (2014) Are applied growth factors able to mimic the positive effects of mesenchymal stem cells on the regeneration of meniscus in the avascular zone? Biomed Res Int 2014:537686

    Article  PubMed  PubMed Central  Google Scholar 

  • Zhang S, Jiang YZ, Zhang W, Chen L, Tong T, Liu W, Mu Q, Liu H, Ji J, Ouyang HW, Zou X (2013) Neonatal desensitization supports long-term survival and functional integration of human embryonic stem cell-derived mesenchymal stem cells in rat joint cartilage without immunosuppression. Stem Cells Dev 22:90–101

    Article  CAS  PubMed  Google Scholar 

  • Zhang S, Chu WC, Lai RC, Lim SK, Hui JHP, Toh WS (2016a) Exosomes derived from human embryonic mesenchymal stem cells promote osteochondral regeneration. Osteoarthr Cartil 24:2135–2140

    Article  CAS  Google Scholar 

  • Zhang W, Ouyang H, Dass CR, Xu J (2016b) Current research on pharmacologic and regenerative therapies for osteoarthritis. Bone Res 4:15040

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Zhang ZZ, Wang SJ, Zhang JY, Jiang WB, Huang AB, Qi YS, Ding JX, Chen XS, Jiang D, Yu JK (2017) 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 45:1497–1511

    Article  PubMed  Google Scholar 

  • Zhu Y, Wu X, Liang Y, Gu H, Song K, Zou X, Zhou G (2016) Repair of cartilage defects in osteoarthritis rats with induced pluripotent stem cell derived chondrocytes. BMC Biotechnol 16:78

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Zhu Y, Wang Y, Zhao B, Niu X, Hu B, Li Q, Zhang J, Ding J, Chen Y, Wang Y (2017) Comparison of exosomes secreted by induced pluripotent stem cell-derived mesenchymal stem cells and synovial membrane-derived mesenchymal stem cells for the treatment of osteoarthritis. Stem Cell Res Ther 8:64

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Zscharnack M, Hepp P, Richter R, Aigner T, Schulz R, Somerson J, Josten C, Bader A, Marquass B (2010) Repair of chronic osteochondral defects using predifferentiated mesenchymal stem cells in an ovine model. Am J Sports Med 38:1857–1869

    Article  PubMed  Google Scholar 

Download references

Acknowledgements

This work was supported by the Universiti Putra Malaysia Research Grant (No. GPIPS/2017/9578600).

Author information

Authors and Affiliations

  1. Institute of Bioscience, Universiti Putra Malaysia, Serdang, 43400, Selangor, Malaysia

    Suleiman Alhaji Muhammad & Sharida Fakurazi

  2. Department of Biochemistry, Usmanu Danfodiyo University, Sokoto, Nigeria

    Suleiman Alhaji Muhammad

  3. Department of Biomedical Science, Faculty of Medicine and Health Sciences, Universiti Putra Malaysia, Serdang, 43400, Selangor, Malaysia

    Norshariza Nordin

  4. Department of Human Anatomy, Faculty of Medicine and Health Sciences, Universiti Putra Malaysia, Serdang, 43400, Selangor, Malaysia

    Muhammad Zulfadli Mehat & Sharida Fakurazi

Authors
  1. Suleiman Alhaji Muhammad
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Norshariza Nordin
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Muhammad Zulfadli Mehat
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Sharida Fakurazi
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Sharida Fakurazi.

Ethics declarations

Conflict of interest

The authors declare that they have no conflicts of interest.

Electronic supplementary material

ESM 1

(DOCX 39 kb)

ESM 2

(PDF 293 kb)

ESM 3

(PDF 2.51 mb)

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Muhammad, S.A., Nordin, N., Mehat, M.Z. et al. Comparative efficacy of stem cells and secretome in articular cartilage regeneration: a systematic review and meta-analysis. Cell Tissue Res 375, 329–344 (2019). https://doi.org/10.1007/s00441-018-2884-0

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00441-018-2884-0

Keywords

Search

Navigation