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Veronesi, Arianna (2015) Nuove strategie manipolative ex vivo per il purging delle unitĂ  di cellule staminali ematopoietiche periferiche destinate al trapianto autologo di midollo. [Tesi di dottorato]

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Abstract (inglese)

NEW MANIPULATIVE STRATEGIES EX VIVO FOR PURGING OF PHERIPHERAL HAEMATOPOIETICS STEM CELLS UNITS AIMED FOR AUTOLOGOUS BONE MARROW TRANSPLANTATION

This thesis aims to evaluate the possibility of using the Gemtuzumab ozogamicin in ex vivo purging of autologous pheripheral blood mononuclear cells, in order to eliminate possible contaminants leukaemia cells. The use of this drug is subject to verification that the depletion of malignant cells does not cause cytotoxic effects on normal stem cells and normal multi-potential progenitors, which are in charge restocking stable and enduring new bone marrow. Therefore, these experiments were conducted by exposing to Gemtuzumab ozogamicin haematopoietic stem cells mobilized in pheripheral blood and haematopoietic stem cells obtained from cord blood determining their "rate of growth" through clonogenic tests.
Based on the above data it can be concluded that:
1) the Gemtuzumab ozogamicin not significantly inhibit the clonal efficiency of subset primitive CD34+/CD38- and mononuclear cells
2) cryopreservation significantly increases the toxic effects of Gemtuzumab ozogamicin probably because of damage to the mambrane, wich promote endocytosis
3) in the clinical purgin, use of Gemtuzumab ozogamicin, should be avoided treatments longer than 24 hs.
These data provide the opportunity for future experiments designed to elucidate the phenomena of toxicity found, and allow to plane clinical trials in order to validate the use of Gemtuzumab ozogamicin in haematopoietic stem cells purging obteined with apheresis methods of acute myeloid leukemia patients elect to the autologous bone marrow transplantation

Abstract (italiano)

NUOVE STRATEGIE MANIPOLATIVE EX VIVO PER IL PURGING DELLE UNITA DI CELLULE STAMINALI EMATOPOIETICHE PERIFERICHE DESTINATE AL TRAPIANTO AUTOLOGO DI MIDOLLO

Questo lavoro di tesi si propone di valutare la possibilità  di utilizzare il Gemtuzumab ozogamicina nel purging ex vivo delle PBSC autologhe, al fine di eliminare le possibili cellule leucemiche contaminanti.
L'impiego di tale farmaco Ăš subordinato alla verifica che la deplezione delle cellule maligne non provochi effetti citotossici sulle cellule staminali pluri/multi potenti normali, alle quali Ăš deputato il ripopolamento stabile e duraturo del midollo osseo.
Pertanto, tale verifica Ăš stata condotta esponendo al Gemtuzumab ozogamicina cellule ematopoietiche mobilizzate nel periferico e cellule ematopoietiche del sangue cordonale e determinando il loro "rate di crescita" mediante test clonogenici su terreno semisolido.
In base ai dati ottenuti Ăš possibile concludere che:
1) il Gemtuzumab ozogamicina non inibisce significativamente l'efficienza clonale del subset primitivo CD34+/CD38- e delle cellule mononucleate normali.
2) Il GO riduce significativamente la crescita clonogenica delle cellule capostipiti granulocitiche-macrofagiche del sangue periferico.
3) La criopreservazione incrementa significativamente gli effetti tossici del GO a causa probabilmente di danni a carico della membrana cellulare, che incentivano l'endocitosi.
4) In previsione di un impiego clinico nel purging del GO, dovranno essere evitati trattamenti superiori alle 24 h.

Questi dati offrono lo spunto per ulteriori future sperimentazioni atte a chiarire i fenomeni di tossicità  rilevati e motivano la pianificazione di trials clinici finalizzati all'impiego del Gemtuzumab ozogamicina nel purging delle cellule staminali emopoietiche raccolte con procedure aferetiche di pazienti affetti da AML eleggibili al trapianto di midollo osseo autologo.

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Tipo di EPrint:Tesi di dottorato
Relatore:Grandi, Claudio
Dottorato (corsi e scuole):Ciclo 26 > Scuole 26 > BIOLOGIA E MEDICINA DELLA RIGENERAZIONE
Data di deposito della tesi:26 Gennaio 2015
Anno di Pubblicazione:26 Gennaio 2015
Parole chiave (italiano / inglese):PURGING / STAMINALI / EMATOPOIETICHE / MIDOLLO PURGING / HAEMATOPOIETICS / STEM CELLS / MARROW
Settori scientifico-disciplinari MIUR:Area 05 - Scienze biologiche > BIO/14 Farmacologia
Struttura di riferimento:Centri > Centro Interdipartimentale di ricerca sulla Biochimica, la Farmacologia, la Fisiopatologia e la terapia del Dolore
Codice ID:7557
Depositato il:10 Nov 2015 12:22
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