Stem cell-based engineering strategies for tendons have yet to yield a normal functional tissue, due in part to a need for tenogenic factors. Additionally, the ability to evaluate differentiation has been challenged by a lack of markers for differentiation. We propose to inform tendon regeneration with developmental cues involved in normal tissue formation and with phenotypic markers that are characteristic of differentiating tendon progenitor cells (TPCs). Mechanical forces, fibroblast growth factor (FGF)-4 and transforming growth factor (TGF)-β2 are implicated in embryonic tendon development, yet the isolated effects of these factors on differentiating TPCs are unknown. Additionally, developmental mechanisms vary between limb and axial tendons, suggesting the respective cell types are programmed to respond uniquely to exogenous factors. To characterize developmental cues and benchmarks for differentiation toward limb vs. axial phenotypes, we dynamically loaded and treated TPCs with growth factors and assessed gene expression profiles as a function of developmental stage and anatomical origin. Based on scleraxis expression, TGFβ2 was tenogenic for TPCs at all stages, while loading was for late-stage cells only, and FGF4 had no effect despite regulation of other genes. When factors were combined, TGF 2 continued to be tenogenic, while FGF4 appeared anti-tenogenic. Various treatments elicited distinct responses by axial vs. limb TPCs of specific stages. These results identified tenogenic factors, suggest tendon engineering strategies should be customized for tissues by anatomical origin, and provide stage-specific gene expression profiles of limb and axial TPCs as benchmarks with which to monitor tenogenic differentiation of stem cells.

If attention is focused on central details at high levels of arousal, memory for peripheral details should be diminished (Easterbrook, 1959). If this is the case, contextual reinstatement (CR) procedures should not enhance memory because these procedures specifically use peripheral information to cue memory. The present experiment tested how arousal influenced eyewitness memory for an event and how it interacts with CR procedures. Participants first viewed one of three series of slides (neutral, arousal, or unusual/control). Memory for central and peripheral details was tested via photo lineups and recognition tests. Although CR procedures enhanced recognition memory for non-arousing and unusual events, they did not affect recognition memory for arousing events. Analyses of the peripheral photo lineup and peripheral recognition test data revealed that CR enhanced the hit rate for the neutral and unusual conditions but not for the arousal condition. Although CR procedures tended to enhance recognition of central information (increasing the hit rate and decreasing the false alarm rate), CR had a smaller enhancement effect in the arousal condition relative to the neutral and unusual conditions. The present experiment also replicates the Christianson and Loftus (1991) finding that peripheral information is not remembered as well in an arousing event, as compared to memory of neutral and unusual events. The theoretical and applied implications of these results are discussed.

IntroductionAdvances in tendon engineering with mesenchymal stem cells (MSCs) are hindered by a need for cues to direct tenogenesis, and markers to assess tenogenic state. We examined the effects of factors involved in embryonic tendon development on adult MSCs, and compared MSC responses to that of embryonic tendon progenitor cells (TPCs), a model system of tenogenically differentiating cells.MethodsMurine MSCs and TPCs subjected to cyclic tensile loading, transforming growth factor-β2 (TGFβ2), and fibroblast growth factor-4 (FGF4) in vitro were assessed for proliferation and mRNA levels of scleraxis, TGFβ2, tenomodulin, collagen type I and elastin.ResultsBefore treatment, scleraxis and elastin levels in MSCs were lower than in TPCs, while other tendon markers expressed at similar levels in MSCs as TPCs. TGFβ2 alone and combined with loading were tenogenic based on increased scleraxis levels in both MSCs and TPCs. Loading alone had minimal effect. FGF4 downregulated tendon marker levels in MSCs but not in TPCs. Select tendon markers were not consistently upregulated with scleraxis, demonstrating the importance of characterizing a profile of markers.ConclusionsSimilar responses as TPCs to specific treatments suggest MSCs have tenogenic potential. Potentially shared mechanisms of cell function between MSCs and TPCs should be investigated in longer term studies.

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