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1.
J Biomater Sci Polym Ed ; 25(17): 1946-61, 2014.
Artigo em Inglês | MEDLINE | ID: mdl-25247724

RESUMO

Recent studies revealing stem cell behavior dependence on mechanical properties of a substrate has initiated the need to probe matrix mechanics and its influence on stem cell fate in a physiologically relevant three-dimensional (3D) microenvironment. We investigated the proliferative and osteogenic potentials of Wharton's jelly mesenchymal stem cells (WJMSCs) immobilized in alginate microspheres with respect to the mechanical properties of alginate hydrogels (1, 1.5 and 2% (w/v)) post incubation in a simulated in vivo environment. Compressive moduli, degradation profile, and swelling kinetics of the hydrogels varied proportionally with alginate concentration and with exposure to simulated conditions. Degradation profile and morphological analysis showed that hydrogels exhibiting high modulus (2% w/v) remained the most intact at the end of day 21. High cell viability in all conditions was observed throughout the culture period. Low-modulus hydrogels (1% w/v) facilitated proliferation of WJMSCs whereas high-modulus hydrogels demonstrated better osteogenic differentiation inferred by an up regulation of osteo-specific genes, expressions of osteocalcin, and quantification of calcium deposition. These findings present a step forward in the development of application-specific hydrogel matrices for stem cell-based tissue engineering.


Assuntos
Materiais Biocompatíveis/química , Materiais Biocompatíveis/farmacologia , Hidrogel de Polietilenoglicol-Dimetacrilato/química , Células-Tronco Mesenquimais/química , Células-Tronco Mesenquimais/citologia , Microesferas , Geleia de Wharton/citologia , Alginatos/química , Cápsulas , Diferenciação Celular/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Células Imobilizadas/citologia , Células Imobilizadas/efeitos dos fármacos , Relação Dose-Resposta a Droga , Humanos , Fenômenos Mecânicos , Células-Tronco Mesenquimais/efeitos dos fármacos , Osteogênese/efeitos dos fármacos
2.
J Cell Mol Med ; 18(2): 344-54, 2014 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-24393246

RESUMO

Clinically reported reparative benefits of mesenchymal stromal cells (MSCs) are majorly attributed to strong immune-modulatory abilities not exactly shared by fibroblasts. However, MSCs remain heterogeneous populations, with unique tissue-specific subsets, and lack of clear-cut assays defining therapeutic stromal subsets adds further ambiguity to the field. In this context, in-depth evaluation of cellular characteristics of MSCs from proximal oro-facial tissues: dental pulp (DPSCs) and periodontal ligament (PDLSCs) from identical donors provides an opportunity to evaluate exclusive niche-specific influences on multipotency and immune-modulation. Exhaustive cell surface profiling of DPSCs and PDLSCs indicated key differences in expression of mesenchymal (CD105) and pluripotent/multipotent stem cell-associated cell surface antigens: SSEA4, CD117, CD123 and CD29. DPSCs and PDLSCs exhibited strong chondrogenic potential, but only DPSCs exhibited adipogenic and osteogenic propensities. PDLSCs expressed immuno-stimulatory/immune-adhesive ligands like HLA-DR and CD50, upon priming with IFNγ, unlike DPSCs, indicating differential response patterns to pro-inflammatory cytokines. Both DPSCs and PDLSCs were hypo-immunogenic and did not elicit robust allogeneic responses despite exposure to IFNγ or TNFα. Interestingly, only DPSCs attenuated mitogen-induced lympho-proliferative responses and priming with either IFNγ or TNFα enhanced immuno-modulation capacity. In contrast, primed or unprimed PDLSCs lacked the ability to suppress polyclonal T cell blast responses. This study indicates that stromal cells from even topographically related tissues do not necessarily share identical MSC properties and emphasizes the need for a thorough functional testing of MSCs from diverse sources with respect to multipotency, immune parameters and response to pro-inflammatory cytokines before translational usage.


Assuntos
Polpa Dentária/citologia , Células-Tronco Mesenquimais/citologia , Ligamento Periodontal/citologia , Adipócitos/citologia , Adipócitos/metabolismo , Antígenos CD/genética , Antígenos CD/metabolismo , Biomarcadores/metabolismo , Diferenciação Celular/efeitos dos fármacos , Proliferação de Células , Células Cultivadas , Condrócitos/citologia , Condrócitos/metabolismo , Polpa Dentária/efeitos dos fármacos , Polpa Dentária/metabolismo , Expressão Gênica , Antígenos HLA-DR/genética , Antígenos HLA-DR/metabolismo , Humanos , Imunofenotipagem , Interferon gama/farmacologia , Células-Tronco Mesenquimais/efeitos dos fármacos , Células-Tronco Mesenquimais/metabolismo , Especificidade de Órgãos , Osteócitos/citologia , Osteócitos/metabolismo , Ligamento Periodontal/efeitos dos fármacos , Ligamento Periodontal/metabolismo , Antígenos Embrionários Estágio-Específicos/genética , Antígenos Embrionários Estágio-Específicos/metabolismo , Fator de Necrose Tumoral alfa/farmacologia
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