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Stefania Cerri, Paolo Spagnolo, Fabrizio Luppi, Luca Richeldi Meeting DAI di Oncologia, Ematologia e Patologie dell ’ Ap

Bando Ricerca Finalizzata 2009 – Ministero della Salute Progetto Giovani Ricercatori. Fibrociti e cellule mesenchimali staminali nella fibrosi polmonare idiopatica. Stefania Cerri, Paolo Spagnolo, Fabrizio Luppi, Luca Richeldi

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Stefania Cerri, Paolo Spagnolo, Fabrizio Luppi, Luca Richeldi Meeting DAI di Oncologia, Ematologia e Patologie dell ’ Ap

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  1. Bando Ricerca Finalizzata 2009 – Ministero della Salute Progetto Giovani Ricercatori Fibrociti e cellule mesenchimali staminali nella fibrosi polmonare idiopatica Stefania Cerri, Paolo Spagnolo, Fabrizio Luppi, Luca Richeldi Meeting DAI di Oncologia, Ematologia e Patologie dell’Apparato Respiratorio Gaiato, 16 luglio 2011

  2. Fibrocytes • Firstly described in 19941 • Circulating, bone marrow-derived cells with the ability to adopt a mesenchymal phenotype • Express a combination of hematopoietic and mesenchymal markers • In normal individuals, approx. 0.5% of circulating leukocytes UNIVERSITY OF MODENA AND REGGIO EMILIA Control Collagen I 1. Bucala R., et al. Molecular Medicine, 1994; 1(1):71-81 SINCE 1175

  3. Fibrocytes markers • They are known to be positive for both CD45 and Collagen I or pro-Collagen I • They may express CD34 (stem cell marker) • According to some authors, they also share monocyte markers (such CD14 and CD11) • Chemokines receptors (such as CXCR4) • Lack of expression of CD3, CD4, CD8, CD19 and CD25 • They seem to be able to present antigens UNIVERSITY OF MODENA AND REGGIO EMILIA SINCE 1175

  4. Fibrocytes in health and disease • Fibrocytes have been described in several diseases in which fibrosis occurs • Asthma • Skin scars and keloids • Scleroderma • Liver fibrosis • Cardiac disease • Renal fibrosis • Circulating fibrocytes may be increased in normal aging UNIVERSITY OF MODENA AND REGGIO EMILIA Herzog EL., Bucala R., Experimental Hematology 2010; 38:548-56 SINCE 1175

  5. IDIOPATHIC PULMONARY FIBROSIS (IPF) Specific form of chronic, progressive fibrosing interstitial pneumonia of unknown cause, occurring in adults and limited to the lungs. UNIVERSITY OF MODENA AND REGGIO EMILIA ATS/ERS/JRS/ALAT IPF GUIDELINES 2011 SINCE 1175

  6. UNIVERSITY OF MODENA AND REGGIO EMILIA SINCE 1175

  7. Pathogenesis of IPFAbnormal wound healing model UNIVERSITY OF MODENA AND REGGIO EMILIA Selman M., Ann Intern Med 2001; 134:136. SINCE 1175

  8. UNIVERSITY OF MODENA AND REGGIO EMILIA SINCE 1175

  9. Circulating fibrocytes in human fibrotic interstitial lung disease UNIVERSITY OF MODENA AND REGGIO EMILIA UIP: usual interstitial pneumonia; NSIP: non-specific interstitial pneumonia Mehrad et al. Biochem Biophys Res Commun 2007; 353:104-8. SINCE 1175

  10. Circulating fibrocytes and IPF prognosis UNIVERSITY OF MODENA AND REGGIO EMILIA Fibrocytes defined as CD45+ and Coll-1+ cells among live PBMC Moeller et al. Am J Respir Crit Care Med 2009; 179:588-94. SINCE 1175

  11. Circulating fibrocytes and IPF prognosis UNIVERSITY OF MODENA AND REGGIO EMILIA Fibrocytes defined as CD45+ and Coll-1+ cells among live PBMC Moeller et al. Am J Respir Crit Care Med 2009; 179:588-94. SINCE 1175

  12. AGE MATTERS • Ageing mice develop more fibrosis in response to Bleomycin, have more fibrocytes Xu J. et al. J Gerontol A Biol Sci Med Sci 2009 • MSCs of ageing mice have decreased ability to differentiate

  13. Mesenchymal stem cell engraftment in lung is enhanced in response to bleomycinexposure and ameliorates its fibrotic effects Saline Bleomycin Bleomycin + BM-MSC Ortiz LA et al. PNAS 2003; 100(14):8407-11.

  14. MESENCHYMAL PROGENITOR CELLS AS BIOMARKERS IN IDIOPATHIC PULMONARY FIBROSIS:A PROSPECTIVE STUDY IL PROGETTO UNIVERSITY OF MODENA AND REGGIO EMILIA GR-2009-1607498 SINCE 1175

  15. Project aims • Aim 1 Measurement and characterization of circulating fibrocytes • Longitudinal measurement of circulating fibrocytes in IPF patients and comparison with clinical outcomes • Characterization of expression markers related to lung homing and differentiation • Assessment of cytokine levels in the serum of IPF patients • Evaluation of the effects of cytokine stimulation on in vitro proliferation, differentiation and migration ability of fibrocytes isolated from IPF patients.

  16. Project aims • Aim 2 Measurement and characterization of MSC • Characterization of bone-marrow derived MSC from IPF patients (numbers and expression markers) • Correlation between MCS and fibrocytes numbers • In vitro assessment of differentiation potential of MSC derived from IPF patients.

  17. Study design • Total duration: 3 years • Patients with a diagnosis of IPF according to ATS/ERS/JRS Guidelines 2011 • Prospective enrollment of both prevalent and incident cases • Collection of blood samples for fibrocytes and cytokine measurement at the enrollment and then every 6 months during the follow-up • Bone marrow samples UNIVERSITY OF MODENA AND REGGIO EMILIA SINCE 1175

  18. “Working group” Stefania Cerri Fabrizio Luppi Paolo Spagnolo Francesca Panico Luca Richeldi with precious feedback and suggestions from Giulia Grisendi Massimo Dominici UNIVERSITY OF MODENA AND REGGIO EMILIA SINCE 1175

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