The multiple pathological cascades activated after traumatic brain injury (TBI) and their extended nature offer the possibility for therapeutic interventions possibly affecting multiple injury mechanisms simultaneously. Mesenchymal stromal cell (MSC) therapy matches this need, being a bioreactor of a variety of molecules able to interact and modify the injured brain microenvironment. Compared to autologous MSCs, bank stored GMP-graded allogenic MSCs appear to be a realistic choice for TBI in a translational perspective, due to the need of delivering cell therapy in the acute phase of the pathology and promptly interact with the damaged tissue and maximize neuroprotective and restorative processes. Allogenic transplant poses the risk of host rejection due to immunological mismatch and introduces the critical issue of immunosuppression. In TBI patients immunosuppression is associated with an increased susceptibility to infections which is directly related to unfavorable outcomes and thus deserves careful consideration. Today no direct comparison of MSC efficacy in immunocompetent and immunosuppressed hosts has been performed. In this thesis we analyzed whether long-term efficacy of human bone marrow MSCs in traumatized mice brain is dependent or not on immunosuppressive treatment, in order to address this important preclinical issue. By observing a similar degree of protection in immunocompetent compared to immunosuppressed mice our data represent a forward step towards the definition of a clinical protocol and provide a strong rational to further investigate the potential of human BM MSC in TBI. In the second part of the thesis, using the same MSC source and the same injury/treatment protocol we focused on mechanistic insight of MSC effect after injury and analyzed the interaction between infused MSCs and resident/recruited immune cerebral cells. In particular we investigated the effects of MSC treatment on the activation and functional changes of microglia/macrophages after TBI and how these phenotypical changes are related to microenvironmental beneficial effects.
(2014). Mesenchymal stromal cells for traumatic brain injury. (Tesi di dottorato, Università degli Studi di Milano-Bicocca, 2014).
|Data di pubblicazione:||15-lug-2014|
|Co-tutore:||ZANIER, ELISA R|
|Titolo:||Mesenchymal stromal cells for traumatic brain injury|
|Settore Scientifico Disciplinare:||BIO/13 - BIOLOGIA APPLICATA|
|Scuola di dottorato:||Scuola di Dottorato in Medicina Traslazionale e Molecolare|
|Corso di dottorato:||SCUOLA DI DOTTORATO IN MEDICINA TRASLAZIONALE E MOLECOLARE (DIMET) - 72R|
|Citazione:||(2014). Mesenchymal stromal cells for traumatic brain injury. (Tesi di dottorato, Università degli Studi di Milano-Bicocca, 2014).|
|Parole Chiave (Inglese):||traumatic brain injury, mesenchymal stromal cells, cell therapy, Cyclosporine, immunosuppression, microglia, immunomodulation, brain protection, brain repair, regeneration|
|Appare nelle tipologie:||07 - Tesi di dottorato Bicocca post 2009|