Martino Introna

Ospedale Papa Giovanni XXIII

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Co-Authors

Josée Golay

Ospedale Papa Giovanni XXIII

141

Alessandro Rambaldi

Ospedale Papa Giovanni XXIII

108

Alberto Mantovani

Humanitas University

Andrea Biondi

University of Milano-Bicocca

Chiara Capelli

Ospedale Papa Giovanni XXIII

Giuseppe Gaipa

Azienda Ospedaliera San Gerardo

Gianmaria Borleri

Ospedale Papa Giovanni XXIII

Elisa Gotti

Ospedale Papa Giovanni XXIII

Paola Allavena

IRCCS Humanitas Research Hospital

Adriana Balduzzi

University of Milano-Bicocca

Cooperative Institutions

Istituti di Ricovero e Cura a Carattere Scientifico

295

Mario Negri Institute for Pharmacological Research

211

University of Milan

195

University of Milano-Bicocca

113

Ospedale Papa Giovanni XXIII

101

Azienda Ospedaliero Universitaria Ospedali Riuniti

Azienda Ospedaliera San Gerardo

University of Bergamo

Inserm

Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico

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Platelet-lysate-Expanded Mesenchymal Stromal Cells as a Salvage Therapy for Severe Resistant Graft-versus-Host Disease in a Pediatric Population

Biology of Blood and Marrow Transplantation (2010)

Giovanna Lucchini Martino Introna Erica Dander Attilio Rovelli Adriana Balduzzi

Despite advances in graft-versus-host-disease (GVHD) treatment, it is estimated that overall survival (OS) at 2 years for hematopoietic cell transplantation (HCT) recipients who experience steroid-resistant GVHD is 10%. Among recent therapeutic approaches for GVHD treatment, mesenchymal stromal cells (MSCs) hold a key position. We describe a multicenter experience of 11 pediatric patients diagnosed with acute or chronic GVHD (aGVHD, cGVHD) treated for compassionate use with GMP-grade unrelated HLA-disparate donors' bone marrow-derived MSCs, expanded in platelet-lysate (PL)-containing medium. Eleven patients (aged 4-15 years) received intravenous (i.v.) MSCs for aGVHD or cGVHD, which was resistant to multiple lines of immunosuppression. The median dose was 1.2 × 10⁶/kg (range: 0.7-3.7 × 10⁶/kg). No acute side effects were observed, and no late side effects were reported at a median follow-up of 8 months (range: 4-18 months). Overall response was obtained in 71.4% of patients, with complete response in 23.8% of cases. None of our patients presented GVHD progression upon MSC administration, but 4 patients presented GVHD recurrence 2 to 5 months after infusion. Two patients developed chronic limited GVHD. This study underlines the safety of PL-expanded MSC use in children. MSC efficacy seems to be greater in aGVHD than in cGVHD, even after failure of multiple lines of immunosuppression.

Immunosuppression

Salvage therapy

10.1016/j.bbmt.2010.03.017

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Citations (178)

Effect of a streptococcal preparation (OK432) on natural killer activity of tumour-associated lymphoid cells in human ovarian carcinoma and on lysis of fresh ovarian tumour cells

British Journal of Cancer (1983)

Francesco Colotta Alessandro Rambaldi Nicoletta Colombo L Tabacchi Martino Introna

Percoll

K562 cells

10.1038/bjc.1983.224

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Citations (30)

Adipose-derived mesenchymal stromal/stem cells in systemic sclerosis: Alterations in function and beneficial effect on lung fibrosis are regulated by caveolin-1

Journal of Scleroderma and Related Disorders (2019)

Rebecca Lee Nicoletta Del Papa Martino Introna Charles Reese Marina Zemskova

The potential value of mesenchymal stromal/stem cell therapy in treating skin fibrosis in scleroderma (systemic sclerosis) and of the caveolin-1 scaffolding domain peptide in treating lung, skin, and heart fibrosis is known. To understand how these observations may relate to differences between mesenchymal stromal/stem cells from healthy subjects and subjects with fibrosis, we have characterized the fibrogenic and adipogenic potential of adipose-derived mesenchymal stromal/stem cells from systemic sclerosis patients, from mice with fibrotic lung and skin disease induced by systemic bleomycin treatment, and from healthy controls. Early passage systemic sclerosis adipose-derived mesenchymal stromal/stem cells have a profibrotic/anti-adipogenic phenotype compared to healthy adipose-derived mesenchymal stromal/stem cells (low caveolin-1, high α-smooth muscle actin, high HSP47, low pAKT, low capacity for adipogenic differentiation). This phenotype is mimicked by treating healthy adipose-derived mesenchymal stromal/stem cells with transforming growth factor beta or caveolin-1 small interfering RNA and is reversed in systemic sclerosis adipose-derived mesenchymal stromal/stem cells by treatment with caveolin-1 scaffolding domain peptide, but not scrambled caveolin-1 scaffolding domain peptide. Similar results were obtained with adipose-derived mesenchymal stromal/stem cells from systemic sclerosis patients and from bleomycin-treated mice, indicating the central role of caveolin-1 in mesenchymal stromal/stem cell differentiation in fibrotic disease.

Caveolin 1

10.1177/2397198318821510

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Citations (13)

Ibrutinib interferes with the cell-mediated anti-tumor activities of therapeutic CD20 antibodies: implications for combination therapy

Haematologica (2014)

Fabio Da Roit Patrick J. Engelberts Ronald P. Taylor Esther C.W. Breij Giuseppe Gritti

The novel Bruton tyrosine kinase inhibitor ibrutinib and phosphatidyl-4-5-biphosphate 3-kinase-δ inhibitor idelalisib are promising drugs for the treatment of chronic lymphocytic leukemia and B-cell non-Hodgkin lymphoma, either alone or in combination with anti-CD20 antibodies. We investigated the possible positive or negative impact of these drugs on all known mechanisms of action of both type I and type II anti-CD20 antibodies. Pretreatment with ibrutinib for 1 hour did not increase direct cell death of cell lines or chronic lymphocytic leukemia samples mediated by anti-CD20 antibodies. Pre-treatment with ibrutinib did not inhibit complement activation or complement-mediated lysis. In contrast, ibrutinib strongly inhibited all cell-mediated mechanisms induced by anti-CD20 antibodies rituximab, ofatumumab or obinutuzumab, either in purified systems or whole blood assays. Activation of natural killer cells, and antibody-dependent cellular cytotoxicity by these cells, as well as phagocytosis by macrophages or neutrophils were inhibited by ibrutinib with a half maximal effective concentration of 0.3-3 μM. Analysis of anti-CD20 mediated activation of natural killer cells isolated from patients on continued oral ibrutinib treatment suggested that repeated drug dosing inhibits these cells in vivo. Finally we show that the phosphatidyl-4-5-biphosphate 3-kinase-δ inhibitor idelalisib similarly inhibited the immune cell-mediated mechanisms induced by anti-CD20 antibodies, although the effects of this drug at 10 μM were weaker than those observed with ibrutinib at the same concentration. We conclude that the design of combined treatment schedules of anti-CD20 antibodies with these kinase inhibitors should consider the multiple negative interactions between these two classes of drugs.

10.3324/haematol.2014.107011

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Citations (145)

Monocyte function in intravenous drug abusers with lymphadenopathy syndrome and in patients with acquired immunodeficiency syndrome: selective impairment of chemotaxis.

PubMed (1985)

Guido Poli Barbara Bottazzi Raffaella Acero L Bersani V Rossi

We have investigated monocyte function in 17 intravenous drug abusers with the clinical and laboratory features of lymphadenopathy syndrome (LAS). LAS patients had normal numbers of circulating monocytes. Monocytes from LAS patients were comparable to cells from normal donors in terms of phagocytosis of latex beads, interleukin-1 secretion, O2- release and killing of antibody-sensitized lymphoma cells or actinomycin D pretreated WEHI 164 cells. In contrast 13 out of 17 LAS subjects tested in this respect as well as six out of nine AIDS patients showed a marked defect of monocyte chemotaxis. Thus monocytes from patients with LAS or AIDS have a selective defect of monocyte chemotaxis.

Monocyte

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Citations (135)

Autologous Mesenchymal Stromal Cell Therapy for Idiopathic Nephrotic Syndrome: The MESNEPH Study

Journal of the American Society of Nephrology (2021)

Marina Vivarelli Mattia Algeri Norberto Perico Federica Casiraghi Francesco Emma

Cell therapy

10.1681/asn.20213210s1827d

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Citations (0)

Manufacturing of Mesenchymal Stromal Cells for the Treatment of Graft-Versus-Host Disease: A Survey within the European Society of Blood and Marrow Transplantation

Blood (2016)

Cristina Trento Maria Ester Bernardo Arnon Nagler Selim Kuçi Martin Bornhäuser

Platelet lysate

Cord blood

Tissue bank

10.1182/blood.v128.22.3374.3374

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Citations (0)

The effect of oral supplementation with legume derived superoxide dismutase on erythrocyte superoxide dismutase in healthy volunteers

Martino Introna D. C. J. ffrey Moos Robert A. Ronzio

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Citations (2)

New Isoforms of the ZFM1 Gene: a Growing Family of Signal Transduction and Activator of RNA (STAR) Proteins

Hämatologie und Bluttransfusion (1998)

Orietta Spinelli Ricardo Amaru Tiziano Barbui Alessandro Rambaldi Corrado Caslini

GRB2

10.1007/978-3-642-71960-8_22

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Citations (0)

Inhibition of natural killer activity by tumor-associated lymphoid cells from ascites ovarian carcinomas.

PubMed (1981)

Paola Allavena Martino Introna Costantino Mangioni Alberto Mantovani

Tumor-associated lymphocytes (TAL) were isolated from ascites ovarian tumors by stepwise application of density and velocity sedimentation on discontinuous Ficoll-Hypaque gradients and fetal bovine serum. TAL had low levels of natural killer (NK) activity compared to levels of peripheral blood lymphocytes (PBL) from the same patients or control subjects. When TAL were mixed with PBL, significant inhibition of NK activity was observed in 7 of 27 patients tested, with the suppression levels ranging from 14 to 60%. Inhibition of PBL NK activity was observed at the ratio of TAL to PBL of 1:1 or 2:1. Suppression of NK activity was detected with effector-to-target cell ratios ranging from 6:1 to 25:1 and at incubation time from 4 to 20 hours in the cytolysis assay. Tumor-associated macrophages from 6 patients were tested for suppression of NK activity. Only with 1 donor was a 17% inhibition observed at a ratio of macrophages of PBL of 1:1. Thus suppression by mature plastic adherent macrophages does not play a major role in the determination of the low levels of NK in human ascites ovarian tumors and the inhibitory activity of suppressor TAL, which had a minor contamination (less than 5%) with mononuclear phagocytes. When TAL from 1 patient with suppressive activity were passed through nylon wool, inhibition of NK activity was observed with both adherent and nonadherent cells.

Ficoll

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Citations (40)