Concise Review: Translating Regenerative Biology into Clinically Relevant Therapies: Are We on the Right Path?

Despite approaches in regenerative medicine using stem cells, bio-engineered scaffolds, and targeted drug delivery to enhance human tissue repair, clinicians remain unable to regenerate large-scale, multi-tissue defects in situ. The study of regenerative biology using mammalian models of complex tissue regeneration offers an opportunity to discover key factors that stimulate a regenerative rather than fibrotic response to injury. For example, although primates and rodents can regenerate their distal digit tips, they heal more proximal amputations with scar tissue. Rabbits and African spiny mice re-grow tissue to fill large musculoskeletal defects through their ear pinna, while other mammals fail to regenerate identical defects and instead heal ear holes through fibrotic repair. This Review explores the utility of these comparative healing models using the spiny mouse ear pinna and the mouse digit tip to consider how mechanistic insight into reparative regeneration might serve to advance regenerative medicine. Specifically, we consider how inflammation and immunity, extracellular matrix composition, and controlled cell proliferation intersect to establish a pro-regenerative microenvironment in response to injuries. Understanding how some mammals naturally regenerate complex tissue can provide a blueprint for how we might manipulate the injury microenvironment to enhance regenerative abilities in humans

Fgf-Signaling Is Compartmentalized Within the Mesenchyme and Controls Proliferation During Salamander Limb Development

Although decades of studies have produced a generalized model for tetrapod limb development, urodeles deviate from anurans and amniotes in at least two key respects: their limbs exhibit preaxial skeletal differentiation and do not develop an apical ectodermal ridge (AER). Here, we investigated how Sonic hedgehog (Shh) and Fibroblast growth factor (Fgf) signaling regulate limb development in the axolotl. We found that Shh-expressing cells contributed to the most posterior digit, and that inhibiting Shh-signaling inhibited Fgf8 expression, anteroposterior patterning, and distal cell proliferation. In addition to lack of a morphological AER, we found that salamander limbs also lack a molecular AER. We found that amniote and anuran AER-specific Fgfs and their cognate receptors were expressed entirely in the mesenchyme. Broad inhibition of Fgf-signaling demonstrated that this pathway regulates cell proliferation across all three limb axes, in contrast to anurans and amniotes where Fgf-signaling regulates cell survival and proximodistal patterning

The Effects of Fraternity/Sorority Membership on College Experiences and Outcomes: A Portrait of Complexity

This study estimated the effects of fraternity/sorority membership on a wide range of college experiences and outcomes for first-year and senior college students at a large, public, Midwestern university. The findings suggest a complex portrait of the relationships between affiliation, engagement, and learning outcomes. Fraternity/sorority membership appeared to facilitate social involvement during college but may have limited the diversity of relationships. It was associated with higher levels of community service, but also increased the odds of excessive alcohol use. In the presence of controls for important, confounding influences, being a fraternity/sorority member had little consistent influence on grades or perceived impact of college. There was little support for gender differences in the impact of affiliation. Finally, implications for student affairs professionals in their work with undergraduate fraternity/sorority leaders and members were considered

Macrophages Are Necessary for Epimorphic Regeneration in African Spiny Mice

How the immune system affects tissue regeneration is not well understood. In this study, we used an emerging mammalian model of epimorphic regeneration, the African spiny mouse, to examine cell-based inflammation and tested the hypothesis that macrophages are necessary for regeneration. By directly comparing inflammatory cell activation in a 4 mm ear injury during regeneration (Acomys cahirinus) and scarring (Mus musculus), we found that both species exhibited an acute inflammatory response, with scarring characterized by stronger myeloperoxidase activity. In contrast, ROS production was stronger and more persistent during regeneration. By depleting macrophages during injury, we demonstrate a functional requirement for these cells to stimulate regeneration. Importantly, the spatial distribution of activated macrophage subtypes was unique during regeneration with pro-inflammatory macrophages failing to infiltrate the regeneration blastema. Together, our results demonstrate an essential role for inflammatory cells to regulate a regenerative response