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Doctoral Thesis
DOI
10.11606/T.42.2012.tde-30012013-093616
Document
Author
Full name
Ênio José Bassi
Institute/School/College
Knowledge Area
Date of Defense
Published
São Paulo, 2012
Supervisor
Committee
Câmara, Niels Olsen Saraiva (President)
Calich, Vera Lucia Garcia
Labriola, Leticia
Nardi, Nance Beyer
Santos, Marinilce Fagundes dos
Title in Portuguese
Propriedades imunomoduladoras das células-tronco mesenquimais do tecido adiposo no tratamento do diabetes autoimune experimental.
Keywords in Portuguese
Auto-imunidade
Camundongos
Células-tronco
Diabetes mellitus
Imunologia celular
Tecido adiposo
Abstract in Portuguese
As células-tronco isoladas a partir do tecido adiposo (ADMSCs) se tornaram promissoras para o tratamento de diversas doenças autoimunes devido a suas propriedades imunomoduladoras. O objetivo deste estudo foi avaliar o potencial terapêutico das ADMSCs em modular a resposta imune no diabetes autoimune experimental em camundongos NOD. ADMSC alogênicas foram administradas em camundongos NOD diabéticos (glicemia > 240 mg/dl) nos dias 0, 7 e 14 sendo então a glicemia monitorada por 12 semanas. A administração de ADMSCs resultou na reversão da hiperglicemia em 78% dos animais por 8 semanas após o tratamento. O tratamento com ADMSCs pôde melhorar de forma efetiva o diabetes autoimune em camundongos NOD pela atenuação da resposta autoimune envolvida concomitante a expansão de células T reguladoras, provendo o desenvolvimento futuro de novas perspectivas de estratégias terapêuticas de terapia celular para o DMT1.
Title in English
Immune regulatory properties of adipose-derived mesenchymal stem cells in the treatment of experimental autoimmune diabetes.
Keywords in English
Autoimmunity
Cellular immunology
Diabetes mellitus
Fat
Mice
Stem cells
Abstract in English
Adipose-derived mesenchymal stem cells (ADMSCs) display immunosuppressive properties representing a promising therapeutic approach for several autoimmune diseases. The aim of this study was to investigate the immune regulatory properties of allogeneic ADMSCs therapy in T cell-mediated experimental autoimmune diabetes in NOD mice. Diabetic NOD mice (blood glucose > 240 mg/dl) were treated or not with ADMSC at days 0, 7 and 14 and blood glucose was monitored once a week for 12 weeks after treatment. ADMSC reversed the hyperglycemia levels of early onset T1D in 78% of diabetic-treated mice for 8 weeks after treatment. ADMSC therapy efficiently ameliorates T1D pathogenesis in diabetic NOD mice by attenuating the Th1 immune response concomitantly with the expansion of Treg cells, thereby contributing to maintenance of functional -cells. This study may thus provide a new therapeutic perspective for the development of ADMSC-based cellular therapies for T1D.
 
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Publishing Date
2013-03-21
 
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