Intra-articular injection of culture-expanded mesenchymal stem cells with or without addition of platelet-rich plasma is effective in decreasing pain and symptoms in knee osteoarthritis: a controlled, double-blind clinical trial

  • Ricardo Bastos
  • Marcelo Mathias
  • Renato Andrade
  • Ronaldo J. F. C. Amaral
  • Vinicius Schott
  • Alex Balduino
  • Raquel Bastos
  • J. Miguel Oliveira
  • Rui L. Reis
  • Scott Rodeo
  • João Espregueira-MendesEmail author



To compare the clinical and laboratory outcomes of intra-articular injections of culture-expanded bone-derived mesenchymal stem cells (MSCs) with or without platelet-rich plasma (PRP) to intra-articular corticosteroid injections for the treatment of knee osteoarthritis (OA).


Forty-seven patients with radiographic and symptomatic knee OA were randomized into three groups for intra-articular injections: autologous bone marrow-derived culture-expanded MSCs (n = 16); autologous bone marrow-derived culture-expanded MSCs + PRP (n = 14); and corticosteroid (n = 17). The outcomes were assessed by the Knee Injury and Osteoarthritis Outcome Score (KOOS) and range of motion (ROM) at baseline, 1, 2, 3, 6, 9 and 12 months and intra-articular cytokines analysis at baseline, 6 and 12 months postoperatively.


The three groups showed significant improvement in most KOOS domains and global score at 1st month and all domains and global score at 12-month follow-up (p < 0.05). At the 1st month, only the MSCs group showed significant differences in KOOS symptoms domain (p = 0.003). The MSCs and MSCs + PRP groups showed the highest percentage of improvement in most KOOS domains and global score compared to the corticosteroid group. All three groups showed a significant reduction in intra-articular levels of human interleukin-10 cytokine, from baseline to 12 months (p < 0.05).


An intra-articular injection of bone marrow-derived culture-expanded MSCs with or without the addiction of PRP is effective in improving the function and decreasing symptoms caused by knee OA at 12-month follow-up.

Level of evidence



Osteoarthritis Mesenchymal stem cells Intra-articular injection Platelet-rich plasma 



The authors would like to sincerely acknowledge ESHO Empresa de Serviços Hospitalares S.A and Keila Mara Cassiano.

Author contributions

RB, RB, MM, SR: conceptualized and designed the work; participated in the patient’s follow-up, acquisition, analysis, interpretation of data. RB, RA: drafted the work. VS, RFA, SR, JEM: revising it critically for important intellectual content; analyzed and interpreted the data. RFA, AB: biologists involved in platelet-rich plasma preparation protocol and procedures, and the culture-expanded MSCs procedures. RB: anesthesiologist physician involved in surgical procedures. RLR, JMO: senior biologists responsible for interpretation of the results and translation interpretation to clinical applications. All author approved the final version to be published.


The authors report no financial funding.

Compliance with ethical standards

Conflict of interest

No financial or non-financial competing interest exists for this manuscript. The manuscript was not influenced by personal or financial relationship with other people or organizations.

Ethical approval

Comissão Nacional de Ética em Pesquisa (Brazilian National Ethics in Research Committee)–CONEP, under number 14878813.4.0000.5533.

Supplementary material

167_2019_5732_MOESM1_ESM.docx (17 kb)
Supplementary material 1 (DOCX 19 kb)


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Copyright information

© European Society of Sports Traumatology, Knee Surgery, Arthroscopy (ESSKA) 2019

Authors and Affiliations

  • Ricardo Bastos
    • 1
    • 2
    • 3
    • 4
    • 5
    • 15
  • Marcelo Mathias
    • 2
  • Renato Andrade
    • 1
    • 3
    • 6
  • Ronaldo J. F. C. Amaral
    • 7
    • 8
    • 9
  • Vinicius Schott
    • 2
  • Alex Balduino
    • 10
  • Raquel Bastos
    • 11
  • J. Miguel Oliveira
    • 4
    • 5
    • 12
  • Rui L. Reis
    • 4
    • 5
    • 12
  • Scott Rodeo
    • 13
  • João Espregueira-Mendes
    • 1
    • 3
    • 5
    • 14
    Email author
  1. 1.Clínica do Dragão, Espregueira-Mendes Sports Centre - FIFA Medical Centre of ExcellencePortoPortugal
  2. 2.Universidade Federal FluminenseNiteróiBrazil
  3. 3.Dom Henrique Research CentrePortoPortugal
  4. 4.3B’s Research Group–Biomaterials, Biodegradables and Biomimetics, Headquarters of the European Institute of Excellence on Tissue Engineering and Regenerative MedicineUniversity of MinhoGuimarãesPortugal
  5. 5.ICVS/3B’s–PT Government Associate LaboratoryBraga/GuimarãesPortugal
  6. 6.Faculty of SportsUniversity of PortoPortoPortugal
  7. 7.Kearney Lab, Department of AnatomyRoyal College of Surgeons in Ireland (RCSI)Dublin 2Ireland
  8. 8.Tissue Engineering Research Group, Department of AnatomyRCSIDublin 2Ireland
  9. 9.Centre for Research in Medical Devices (CURAM)National University of Ireland GalwayGalwayIreland
  10. 10.ExcellionNireóiBrazil
  11. 11.Hospital LusíadasPortoPortugal
  12. 12.The Discoveries Centre for Regenerative and Precision MedicineHeadquarters at University of MinhoGuimarãesPortugal
  13. 13.Sports Medicine and Shoulder SurgeryHospital for Special SurgeryNew YorkUSA
  14. 14.Orthopaedics Department of Minho UniversityBragaPortugal
  15. 15.The Biomechanics Group, Department of Mechanical EngineeringImperial College LondonLondonEngland

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