La terapia mediante l’uso di cellule staminali allogeniche è una potenziale alternativa per la cura di malattie infiammatorie e degenerative. Vari gruppi di ricerca hanno messo in luce le proprietà immunomodulatorie di varie cellule staminali, come per esempio le cellule mesenchimali stromali, ma al momento non è stato ancora fatto uno studio comparativo mostrante differenze qualitative e quantitative delle proprietà immunoregolatorie di staminali di diversa origine. Lo scopo del lavoro è stato quindi quello di confrontare le proprietà immunologiche di varie cellule staminali, tra cui cellule mesenchimali stromali di origine midollare, cellule staminali olfattorie, cellule staminali isolate da leptomeningi, e tre tipi di cellule staminali esprimenti il recettore c-Kit, ovvero cellule staminali del fluido amniotico, cellule staminali cardiache e cellule staminali polmonari. Tutte queste tipologie cellulari mostravano caratteristiche immunologiche comuni, come per esempio l’espressione dei marcatori attivatori ICAM-1, VCAM-1, HLA-ABC, e HLA-DR, e quando coltivate con linfociti T, NK e B purificati, erano in grado di regolarne la proliferazione. Il trattamento con citochine infiammatorie riduceva l’immunogenicità delle staminali analizzate nei confronti di linfociti NK rispetto alle cellule controllo, e induceva l’espressione dell’indolamina-2,3 diossigenasi (IDO) responsabile dell’immunosoppressione dei linfociti T. Infine, tutte le cellule staminali analizzate mostravano un effetto anti-apoptotico nei confronti delle cellule effettrici immuni non stimolate. Inoltre, in questo lavoro abbiamo mostrato che l’effetto immunosoppressivo non è una proprietà costitutiva delle cellule staminali, ma è una conseguenza dell’induzione mediata da citochine infiammatorie, effetto precedente mostrato per le cellule mesenchimali stromali. L’immunoregolazione è una proprietà condivisa da vari tipi di cellule staminali, e una caratterizzazione più approfondita di questo meccanismo potrebbe essere fondamentale per il loro uso terapeutico.
Allogeneic stem cell (SC)-based therapy is a promising tool for the treatment of a range of human degenerative and inflammatory diseases. Many reports highlighted the immune modulatory properties of some SC types, such as mesenchymal stromal cells (MSCs), but a comparative study with SCs of different origin, to assess whether immune regulation is a general SC property, is still lacking. To this aim, we applied highly standardized methods employed for MSC characterization to compare the immunological properties of bone marrow (BM)-MSCs, olfactory ectomesenchymal SCs (OE-MSCs), leptomeningeal SCs (LeSCs), and three different c-Kit-positive SC types, that is, amniotic fluid SCs (AFSCs), cardiac SCs (CSCs), and lung SCs (LSCs). We found that all the analyzed human SCs share a common pattern of immunological features, in terms of expression of activation markers ICAM-1, VCAM-1, HLA-ABC, and HLA-DR, modulatory activity toward purified T, B, and NK cells, lower immunogenicity of inflammatory-primed SCs as compared to resting SCs, and indoleamine-2,3-dioxygenase (IDO)-activation as molecular inhibitory pathways, with some SC type-related peculiarities. Moreover, the SC types analyzed exert an anti- apoptotic effect toward not-activated immune effector cells (IECs). In addition, we found that the inhibitory behavior is not a constitutive property of SCs, but is acquired as a consequence of IEC activation, as previously described for MSCs. Thus, immune regulation is a general property of SCs and the characterization of this phenomenon may be useful for a proper therapeutic use of SCs.
Comparative study of immune regulatory properties of stem cells derived from different tissues
Di Trapani, Mariano
2015-01-01
Abstract
Allogeneic stem cell (SC)-based therapy is a promising tool for the treatment of a range of human degenerative and inflammatory diseases. Many reports highlighted the immune modulatory properties of some SC types, such as mesenchymal stromal cells (MSCs), but a comparative study with SCs of different origin, to assess whether immune regulation is a general SC property, is still lacking. To this aim, we applied highly standardized methods employed for MSC characterization to compare the immunological properties of bone marrow (BM)-MSCs, olfactory ectomesenchymal SCs (OE-MSCs), leptomeningeal SCs (LeSCs), and three different c-Kit-positive SC types, that is, amniotic fluid SCs (AFSCs), cardiac SCs (CSCs), and lung SCs (LSCs). We found that all the analyzed human SCs share a common pattern of immunological features, in terms of expression of activation markers ICAM-1, VCAM-1, HLA-ABC, and HLA-DR, modulatory activity toward purified T, B, and NK cells, lower immunogenicity of inflammatory-primed SCs as compared to resting SCs, and indoleamine-2,3-dioxygenase (IDO)-activation as molecular inhibitory pathways, with some SC type-related peculiarities. Moreover, the SC types analyzed exert an anti- apoptotic effect toward not-activated immune effector cells (IECs). In addition, we found that the inhibitory behavior is not a constitutive property of SCs, but is acquired as a consequence of IEC activation, as previously described for MSCs. Thus, immune regulation is a general property of SCs and the characterization of this phenomenon may be useful for a proper therapeutic use of SCs.File | Dimensione | Formato | |
---|---|---|---|
PhD Thesis Mariano Di Trapani.pdf
accesso aperto
Tipologia:
Tesi di dottorato
Licenza:
Dominio pubblico
Dimensione
1.58 MB
Formato
Adobe PDF
|
1.58 MB | Adobe PDF | Visualizza/Apri |
I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.