Collagen I matrix contributes to determination of adult human stem cell lineage via differential, structural conformation-specific elicitation of cellular stress response.

Evidence from laboratory and animal studies provides groundwork for understanding mechanisms and potential before human studies continue.

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• Level B · Emerging clinical evidence with positive signals
• Level C · Early human research exploring benefits
• Level D · Scientific groundwork from lab and animal studies
• Emerging · Emerging topic under active research

Abstract (original English)

Previously, we reported that the conformational transition of collagen I matrix plays, along with differentiation stimuli, a regulatory role in determination of differentiation lineage of bone marrow stromal sells via distinct signaling pathways specific for the structural state of the matrix. The present study addresses mechanisms underlying differential structural conformation-specific effects of collagen matrices on differentiation into diverse lineages. The results obtained suggest that the pivotal player in the observed matrix conformation-mediated regulation is a differential cellular stress response elicited by the exposure to native but not to denatured collagen I matrix. The stress causing such a response appears to be generated by matrix contraction and mediated by Alpha2Beta1 integrins engaged on native but not on denatured collagen I matrix. The principal facet of the observed phenomenon is not the nature of a stress but general stress response: when cells on denatured collagen I matrix are subjected to thermal stress, osteogenic pathway shifts to that seen on native collagen I matrix. Importantly, cellular stress response might be commonly involved in determination of differentiation lineage. Indeed, distinct components of cellular stress response machinery appear to regulate differentiation into diverse lineages. Thus, augmentation of Hsp90 levels enables the oper

Evidence level

Evidence from laboratory and animal studies provides groundwork for understanding mechanisms and potential before human studies continue.

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