Matrix Remodeling Maintains Embryonic Stem Cell Self-Renewal by Activating Stat3

One of the most promising developments in modern medicine is that of embryonic stem cell (ESC) research. While their use and development is steeped in philosophical controversy, medically speaking, they offer great opportunity and have tremendous potential to help people understand and overcome some of the more damaging health conditions known to this day. However, for embryonic stem cell research to be effective and offer solutions to these very conditions, it is important that researchers understand how they work. One process that is not completely clear is that of self-renewal or differentiation. A variety of natural and synthetic matrices have been used to influence ESC development. ESCs also have a robust matrix of their own, but the mechanisms behind these matrices remain largely a mystery. Since matrix metalloproteinases (MMPs) are known to play a key role in the remodeling of the ESC matrix, studying how MMPs interact with ESCs could offer new insight into how extracellular matrices (ECMs) work and can be used to help mitigate the onset of certain conditions.

Adding certain proteins to MMPs could have a significant effect on the development and differentiation of ECMs. For example, matrix bound proteins, such as FGF4, have been found to have a profound effect on self-renewal, but the role of remodeling proteins on self-renewal is yet unknown. Using mouse extracellular matrices (mECMs) and the Amplite Universal Fluorimetric MMP Activity Assay Kit, Przybla et al. from the Massachusetts Institute of Technology looked at what the addition of MMP would do to the self-renewal process of mECMs. By using the Amplite Universal Fluorimetric MMP Activity Assay Kit, the research team was able to study the activity of the MMP and use this information to make important causal inferences about the role of MMP1 on mECM regeneration.

The results of their study stand to have a profound impact on research into the effectiveness and functionality of ECMs. What they found is that the addition of the interstitital collagenase MMP1 is sufficient to maintain long-term leukemia inhibitory factor (LIF)-independent mESC self-renewal in a dose-dependent manner. This occurs largely because the normally-trapped endogenously produced self-renewal-inducing signals are released upon MMP-induced matrix remodeling. This shows that mESCs actually naturally produce sufficient levels of pro-self-renewal ligands, meaning they need to rely less on external substances, whether natural or synthetic, to induce regeneration. The careful monitoring of MMPs provided by the Amplite Universal Fluorimetric MMP Activity Assay Kit helped make obtaining these results possible. Without being able to closely monitor the enzyme's activity, researchers would have been unable to determine the effects it has on ECM self-renewal. It is nearly impossible to track a single MMP enzyme, but being able to measure general activity with the type of accuracy afforded by the Amplite Universal Fluorimetric MMP Activity Assay Kit allows researchers to declare their results with the confidence needed to allow others to build on it. These results will help launch the field of stem cell research to new heights, opening the door for what could be historic scientific achievements.

References

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1. Przybyla, Laralynne M., et al. "Matrix Remodeling Maintains Embryonic Stem Cell Self Renewal by Activating Stat3." Stem cells 31.6 (2013): 1097-1106.