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Circulating microRNA after autologous bone marrow mononuclear cell (BM-MNC) injection in patients with ischemic stroke
  1. Fernando Mancha1,2,
  2. Irene Escudero-Martinez1,3,
  3. Elena Zapata-Arriaza4,
  4. Angela Vega-Salvatierra1,
  5. Juan Antonio Cabezas3,
  6. Lucia Lebrato3,
  7. Blanca Pardo3,
  8. Javier De-La-Torre3,
  9. Montserrat Zapata1,
  10. Virginia Escamilla5,
  11. Cristina Calderón-Cabrera5,
  12. Jesús Martín-Sánchez5,
  13. Roberto Valverde6,
  14. Eduardo Aguera-Morales6,
  15. Inmaculada Herrera7,
  16. Fernando Delgado8,
  17. Miguel Ángel Gamero9,
  18. Soledad Pérez-Sánchez9,
  19. Miguel Moya10,
  20. Raúl Espinosa10,
  21. Joaquín Ortega-Quintanilla4,
  22. Isabel Gutierrez-Jarrin4,
  23. Alejandro González-García1,4,
  24. Joan Montaner9,11,
  25. Francisco Moniche1,3
  1. 1 Neurovascular Laboratory, Instituto de Biomedicina de Sevilla, Sevilla, Spain
  2. 2 Clinical Laboratory, Hospital Santa Barbara, Puertollano, Spain
  3. 3 Neurology, Virgen del Rocio University Hospital, Sevilla, Andalucía, Spain
  4. 4 Interventional Neuroradiology, Virgen del Rocio University Hospital, Sevilla, Andalucía, Spain
  5. 5 Hematology, Virgen del Rocio University Hospital, Sevilla, Andalucía, Spain
  6. 6 Neurology, Reina Sofia University Hospital, Cordoba, Andalucía, Spain
  7. 7 Hematology, Reina Sofia University Hospital, Cordoba, Andalucía, Spain
  8. 8 Interventional Neuroradiology, Reina Sofia University Hospital, Cordoba, Spain
  9. 9 Neurology, Virgen Macarena University Hospital, Sevilla, Andalucía, Spain
  10. 10 Neurology, Hospital Universitario Puerta del Mar, Cadiz, Andalucía, Spain
  11. 11 Neurovascular Laboratory, Vall d'Hebron Hospital, Barcelona, Catalunya, Spain
  1. Correspondence to Dr Francisco Moniche, Neurology, Virgen del Rocio University Hospital, Sevilla, Andalucía 41013, Spain; pmoniche{at}


Previous studies have shown the potential of microRNAs (miRNA) in the pathological process of stroke and functional recovery. Bone marrow mononuclear cell (BM-MNC) transplantation improves recovery in experimental models of ischemic stroke that might be related with miRNA modifications. However, its effect on circulating miRNA has not been described in patients with stroke. We aimed to evaluate the circulating levels of miRNAs after autologous BM-MNC transplantation in patients with stroke. We investigate the pattern of miRNA-133b and miRNA-34a expression in patients with ischemic stroke included in a multicenter randomized controlled phase IIb trial (; unique identifier: NCT02178657). Patients were randomized to 2 different doses of autologous intra-arterial BM-MNC injection (2×106/kg or 5×106/kg) or control group within the first 7 days after stroke onset. We evaluate plasma concentration of miRNA-113b and miRNA-34a at inclusion and 4, 7, and 90 days after treatment. Thirteen cases (8 with 2×106/kg BM-MNC dose and 5 with 5×106/kg dose) and 11 controls (BM-MNC non-treated) were consecutively included. Mean age was 64.1±12.3 with a mean National Institutes of Health Stroke Scale score at inclusion of 14.5. Basal levels of miRNA were similar in both groups. miR-34a-5p and miR-133b showed different expression patterns. There was a significant dose-dependent increase of miRNA-34a levels 4 days after BM-MNC injection (fold change 3.7, p<0.001), whereas miRNA-133b showed a significant increase in the low-dose BM-MNC group at 90 days. Intra-arterial BM-MNC transplantation in patients with ischemic stroke seems to modulate early circulating miRNA-34a levels, which have been related to precursor cell migration in stroke and smaller infarct volumes.

  • stroke
  • adult human bone marrow
  • transplantation
  • microRNAs
  • clinical trial

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  • Contributors Conception and design: FMa, JM, FMo. Financial support: AGG, JM, FMo. Administrative support: AVS, FMa, FMo. Provision of patients: all authors. Collection of data: all authors. Data analysis and interpretation: FMa, JM, FMo. Manuscript writing: FMa, FMo. Final approval of manuscript: all authors.

  • Funding This work has been supported by the grants PI15/01197, PI18/01414 and RD16/0019/0015 (INVICTUS+) from the Spanish Ministry of Economy and Competitiveness, cofunded by ISCIII and FEDER funds; Mutua Madrileña grant. FMa is supported by a Rio Hortega contract (CM16/00015). Andalusian Initiative for Advanced Therapies (IATA) is the sponsor of the trial.

  • Competing interests None declared.

  • Patient consent for publication Not required.

  • Provenance and peer review Not commissioned; externally peer reviewed.

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