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Enhancement of hMSC In Vitro Proliferation by Surface Immobilization of a Hepar...

Cimino, M; Parreira, P; Leiro, V; Sousa, A; Gonçalves, RM; Barrias, CC; Martins, MCL

The use of human Mesenchymal Stem Cells (hMSC) as therapeutic agents for advanced clinical therapies relies on their in vitro expansion. Over the last years, several efforts have been made to optimize hMSC culture protocols, namely by mimicking the cell physiological microenvironment, which strongly relies on signals provided by the extracellular matrix (ECM). ECM glycosaminoglycans, such as heparan-sulfate, se...


Therapeutic strategies for IVD regeneration through hyaluronan/SDF-1-based hydr...

Cunha, C; Pereira, CL; Ferreira, JR; Ribeiro-Machado, C; Grad, S; Santos, SG; Gonçalves, RM

Intervertebral disc (IVD) degeneration involves a complex cascade of events, including degradation of the native extracellular matrix, loss of water content, and decreased cell numbers. Cell recruitment strategies for the IVD have been increasingly explored, aiming to recruit either endogenous or transplanted cells. This study evaluates the IVD therapeutic potential of a chemoattractant delivery system (HAPSDF5...


Modulation of the in vivo inflammatory response by pro-versus anti-inflammatory...

Cunha, C; Teixeira, GQ; Ribeiro-Machado, C; Leite Pereira, C; Ferreira, JR; Molinos, M; Santos, SG; Barbosa, MA; Gonçalves, RM

Inflammation is central in intervertebral disc (IVD) degeneration/regeneration mechanisms, and its balance is crucial to maintain tissue homeostasis. This work investigates the modulation of local and systemic inflammatory response associated with IVD degeneration/herniation by administration of PRO-versus ANTI-inflammatory treatments. Chitosan/poly-¿-glutamic acid nanocomplexes, known as pro-inflammatory (PRO)...


Macrophages down-regulate gene expression of intervertebral disc degenerative m...

Silva, AJ; Ferreira, JR; Cunha, C; Corte-Real, JV; Bessa-Gonçalves, M; Barbosa, MA; Santos, SG; Gonçalves, RM

Low back pain is a highly prevalent clinical problem and intervertebral disc (IVD) degeneration is now accepted as the major pathophysiological mechanism responsible for this condition. Accumulating evidence suggests that inflammation plays a crucial role in the progression of human IVD degeneration, with macrophages being pointed as the key immune cell players in this process since their infiltration in degene...


Genetically engineered-MSC therapies for non-unions, delayed unions and critica...

Freitas, J; Santos, SG; Gonçalves, RM; Teixeira, JH; Barbosa, MA; Almeida, MI

The normal bone regeneration process is a complex and coordinated series of events involving different cell types and molecules. However, this process is impaired in critical-size/large bone defects, with non-unions or delayed unions remaining a major clinical problem. Novel strategies are needed to aid the current therapeutic approaches. Mesenchymal stem/stromal cells (MSCs) are able to promote bone regenerati...


The inflammatory response in the regression of lumbar disc herniation

Cunha, C; Silva, A; Pereira, P; Vaz, R; Gonçalves, RM; Barbosa, MA

Lumbar disc herniation (LDH) is highly associated with inflammation in the context of low back pain. Currently, inflammation is associated with adverse symptoms related to the stimulation of nerve fibers that may lead to pain. However, inflammation has also been indicated as the main factor responsible for LDH regression. This apparent controversy places inflammation as a good prognostic indicator of spontaneou...


Mesenchymal Stromal Cell Secretome: Influencing Therapeutic Potential by Cellul...

Ferreira, JR; Teixeira, GQ; Santos, SG; Barbosa, MA; Almeida-Porada, G; Gonçalves, RM

Mesenchymal stromal cells (MSCs) are self-renewing, culture-expandable adult stem cells that have been isolated from a variety of tissues, and possess multipotent differentiation capacity, immunomodulatory properties, and are relatively non-immunogenic. Due to this unique set of characteristics, these cells have attracted great interest in the field of regenerative medicine and have been shown to possess pronou...


Interferon-gamma at the crossroads of tumor immune surveillance or evasion

Castro, F; Cardoso, AP; Gonçalves, RM; Serre, K; Oliveira, MJ

Interferon-gamma (IFN-¿) is a pleiotropic molecule with associated antiproliferative, pro-apoptotic and antitumor mechanisms. This effector cytokine, often considered as a major effector of immunity, has been used in the treatment of several diseases, despite its adverse effects. Although broad evidence implicating IFN-¿ in tumor immune surveillance, IFN-¿-based therapies undergoing clinical trials have been of...


CITOGENÉTICA DE PRÓXIMA GERAÇÃO: IMPLEMENTAÇÃO E PRIMEIROS RESULTADOS EM PORTUGAL

David, Dezso; Oliva-Teles, Natália; Freixo, J; Fortuna, Ana; Tkachenko, Natalyia; Carvalho, Isabel; Marques, M; Cardoso, M; Fino, J; Marques, Bárbara


Fibrinogen scaffolds with immunomodulatory properties promote in vivo bone rege...

Vasconcelos, DM; Gonçalves, RM; Almeida, CR; Pereira, IO; Oliveira, MI; Neves, N; Silva, AM; Ribeiro, AC; Cunha, C; Almeida, AR; Ribeiro, CC; Gil, AM

The hypothesis behind this work is that fibrinogen (Fg), classically considered a pro-inflammatory protein, can promote bone repair/regeneration. Injury and biomaterial implantation naturally lead to an inflammatory response, which should be under control, but not necessarily minimized. Herein, porous scaffolds entirely constituted of Fg (Fg-3D) were implanted in a femoral rat bone defect and investigated at tw...


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