TY - JOUR
T1 - Phenotypical/functional characterization of in vitro-expanded mesenchymal stromal cells from patients with Crohn's disease BM-derived MSC from patients with Crohn's disease
AU - Bernardo, Maria Ester
AU - Avanzini, Maria Antonia
AU - Ciccocioppo, Rachele
AU - Perotti, Cesare
AU - Cometa, Angela Maria
AU - Moretta, Antonia
AU - Marconi, Massimo
AU - Valli, Monica
AU - Novara, Francesca
AU - Bonetti, Federico
AU - Zuffardi, Orsetta
AU - MacCario, Rita
AU - Corazza, Gino Roberto
AU - Locatelli, Franco
PY - 2009
Y1 - 2009
N2 - Background aims Because of their capacity to modulate the immune response and promote tissue repair, mesenchymal stromal cells (MSC) represent a potential novel treatment for autoimmune/inflammatory diseases, including Crohn's disease (CD). The aim of the study was in vitro characterization of MSC from active CD patients for future clinical application. Methods MSC from the bone marrow (BM) of seven CD patients (median age 32 years) were expanded ex vivo in the presence of 5% platelet lysate; cells were investigated for clonogenic efficiency, proliferative capacity, morphology, immunophenotype, differentiation potential, genetic stability and ability to suppress in vitro proliferation of both autologous and allogeneic lymphocytes to polyclonal mitogens. Results were compared with those of BM MSC of four healthy donors (HD). Results MSC were successfully expanded from all patients. Colony-forming unitfibroblast (CFU-F) frequency and proliferative capacity were comparable in CD and HD MSC. CD MSC showed typical spindle-shaped morphology and differentiated into osteoblasts, adipocytes and chondrocytes. Surface immunologic markers did not differ between CD and HD MSC, with the only exception of sizeable levels of HLA-DR at early culture passages [1284% at passage (P)1] in the former. CD MSC ceased their growth at variable passages (from P8 to P25) and entered senescence without any change in morphology/proliferation rate. Array-comparative genomic hybridization demonstrated that CD MSC do not show imbalanced chromosomal rearrangements. Both CD and HD MSC inhibited in vitro proliferation of lymphocytes to mitogens. Conclusions CD MSC show biologic characteristics similar to HD MSC and can be considered for anti-inflammatory and reparative cell therapy approaches in patients with refractory disease.
AB - Background aims Because of their capacity to modulate the immune response and promote tissue repair, mesenchymal stromal cells (MSC) represent a potential novel treatment for autoimmune/inflammatory diseases, including Crohn's disease (CD). The aim of the study was in vitro characterization of MSC from active CD patients for future clinical application. Methods MSC from the bone marrow (BM) of seven CD patients (median age 32 years) were expanded ex vivo in the presence of 5% platelet lysate; cells were investigated for clonogenic efficiency, proliferative capacity, morphology, immunophenotype, differentiation potential, genetic stability and ability to suppress in vitro proliferation of both autologous and allogeneic lymphocytes to polyclonal mitogens. Results were compared with those of BM MSC of four healthy donors (HD). Results MSC were successfully expanded from all patients. Colony-forming unitfibroblast (CFU-F) frequency and proliferative capacity were comparable in CD and HD MSC. CD MSC showed typical spindle-shaped morphology and differentiated into osteoblasts, adipocytes and chondrocytes. Surface immunologic markers did not differ between CD and HD MSC, with the only exception of sizeable levels of HLA-DR at early culture passages [1284% at passage (P)1] in the former. CD MSC ceased their growth at variable passages (from P8 to P25) and entered senescence without any change in morphology/proliferation rate. Array-comparative genomic hybridization demonstrated that CD MSC do not show imbalanced chromosomal rearrangements. Both CD and HD MSC inhibited in vitro proliferation of lymphocytes to mitogens. Conclusions CD MSC show biologic characteristics similar to HD MSC and can be considered for anti-inflammatory and reparative cell therapy approaches in patients with refractory disease.
KW - Crohn's disease
KW - In vitro expansion
KW - Infl ammation
KW - Mesenchymal stromal cells
KW - Reparative medicine
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U2 - 10.3109/14653240903121260
DO - 10.3109/14653240903121260
M3 - Article
C2 - 19903096
AN - SCOPUS:70450158753
VL - 11
SP - 825
EP - 836
JO - Cytotherapy
JF - Cytotherapy
SN - 1465-3249
IS - 7
ER -