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Projeto de investigação
New approaches for inactivation, treatment and immunoprophylaxy of cryptosporidiosis
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Publicações
Mesenchymal Stem Cells and Biomaterials Systems – Perspectives for Skeletal Muscle Tissue Repair and Regeneration
Publication . Caseiro, A.R.; Pereira, T.; Bártolo, P. J.; Santos, J.D.; Luís, A.L.; Maurício, A.C.
Skeletal muscle is essential in voluntary movement and other major vital functions. Muscle injuries are important in clinical practice and, despite skeletal muscle's good regenerative ability, severe tissue loss impairs complete myofibre regeneration, limiting structural and functional recovery of the affected muscle, eventually leading to the development of non-contractile fibrous scar. The intrinsic healing mechanisms rely in great extent on the residing progenitor population but significant drawbacks to their practical application in regenerative strategies boosted the search for alternative cell sources, such as extra-fetal mesenchymal stem cells (MSCs). MSCs have demonstrated to positively influence the regeneration of different disease models. When severe volumetric muscle tissue loss occurs, the body is seldom capable of replacing the lost portions with fully functional tissue. A rational strategy to aid the healing of such situations is the application of biomaterial implants that provide a structural matrix for the ingrowth of regenerating muscle fibres. Both synthetic and natural biomaterials have been hypothesized for this purpose and some have reached as far clinical cases applications. Obvious improvements are observed in most cases, but reaction to some biomaterials and functional recovery are still a challenge. The addition of MSCs to the biomaterials seems to improve the systems' performance in the overall regenerative milieu. This strategies promote scaffold's vascularization and integration, as well as accelerated tissue ingrowth and reduces scar formation, resulting in improved recovery rates at both structural and functional levels.
Promoting Nerve Regeneration in a Neurotmesis Rat Model Using Poly(DL-lactide-ε-caprolactone) Membranes and Mesenchymal Stem Cells from the Wharton’s Jelly: In Vitro and In Vivo Analysis
Publication . Pereira, T.; Gärtner, A.; Amorim, I.; Almeida, A.; Caseiro, A.R.; Armada-da-Silva, Paulo A. S.; Amado, Sandra; Fregnan, Federica; Varejão, A. S. P.; Santos, J. D.; Bártolo, P. J.; Geuna, S.; Luís, A. L.; Maurício, A. C.
In peripheral nerves MSCs can modulate Wallerian degeneration and the overall regenerative response by acting through paracrine mechanisms directly on regenerating axons or upon the nerve-supporting Schwann cells. In the present study, the effect of human MSCs from Wharton’s jelly (HMSCs), differentiated into neuroglial-like cells associated to poly (DL-lactide-ε-caprolactone) membrane, on nerve regeneration, was evaluated in the neurotmesis injury rat sciatic nerve model. Resultsin vitroshowed successful differentiation of HMSCs into neuroglial-like cells, characterized by expression of specific neuroglial markers confirmed by immunocytochemistry and by RT-PCR and qPCR targeting specific genes expressed.In vivotesting evaluated during the healing period of 20 weeks, showed no evident positive effect of HMSCs or neuroglial-like cell enrichment at the sciatic nerve repair site on most of the functional and nerve morphometric predictors of nerve regeneration although the nociception function was almost normal. EPT on the other hand, recovered significantly better after HMSCs enriched membrane employment, to values of residual functional impairment compared to other treated groups. When the neurotmesis injury can be surgically reconstructed with an end-to-end suture or by grafting, the addition of a PLC membrane associated with HMSCs seems to bring significant advantage, especially concerning the motor function recovery.
MSCs Conditioned Media and Umbilical Cord Blood Plasma Metabolomics and Composition
Publication . Pereira, Tiago; Ivanova, Galya; Caseiro, Ana Rita; Barbosa, Paula; Bártolo, Paulo Jorge; Santos, José Domingos; Luís, Ana Lúcia; Maurício, Ana Colette; Ivanovic, Zoran
Human mesenchymal stem cells (hMSCs) from umbilical cord (UC) blood (UCB) and matrix are tested clinically for a variety of pathologies but in vitro expansion using culture media containing fetal bovine serum (FBS) is essential to achieve appropriate cell numbers for clinical use. Human UCB plasma (hUCBP) can be used as a supplement for hMSCs culture, since UCB is rich in soluble growth factors and due to worldwide increased number of cryopreserved UCB units in public and private banks, without the disadvantages listed for FBS. On the other hand, the culture media enriched in growth factors produced by these hMSCs in expansion (Conditioned medium - CM) can be an alternative to hMSCs application. The CM of the hMSCs from the UC might be a better therapeutic option compared to cell transplantation, as it can benefit from the local tissue response to the secreted molecules without the difficulties and complications associated to the engraftment of the allo- or xeno-transplanted cells. These facts drove us to know the detailed composition of the hUCBP and CM, by 1H-NMR and Multiplexing LASER Bead Technology. hUCBP is an adequate alternative for the FBS and the CM and hUCBP are important sources of growth factors, which can be used in MSCs-based therapies. Some of the major proliferative, chemotactic and immunomodulatory soluble factors (TGF-β, G-CSF, GM-CSF, MCP-1, IL-6, IL-8) were detected in high concentrations in CM and even higher in hUCBP. The results from 1H-NMR spectroscopic analysis of CM endorsed a better understanding of hMSCs metabolism during in vitro culture, and the relative composition of several metabolites present in CM and hUCBP was obtained. The data reinforces the potential use of hUCBP and CM in tissue regeneration and focus the possible use of hUCBP as a substitute for the FBS used in hMSCs in vitro culture.
Unidades organizacionais
Descrição
Palavras-chave
recombinant proteins,antibodies,immunoprophylaxy,infection, Natural sciences
Contribuidores
Financiadores
Entidade financiadora
Fundação para a Ciência e a Tecnologia, I.P.
Programa de financiamento
Concurso para Projectos de I&D em todos os Domínios Científicos - 2008
Número da atribuição
PTDC/CVT/103081/2008