Skeletal muscle possesses remarkable regenerative potential due to satellite cells, an injury-responsive stem cell population located beneath the muscle basal lamina that expresses Pax7. By lineage tracing of progenitor cells expressing the Twist2 (Tw2) transcription factor in mice, we discovered a myogenic lineage that resides outside the basal lamina of adult skeletal muscle. Tw2+ progenitors are molecularly and anatomically distinct from satellite cells, are highly myogenic in vitro, and can fuse with themselves and with satellite cells. Tw2+ progenitors contribute specifically to type IIb/x myofibers during adulthood and muscle regeneration, and their genetic ablation causes wasting of type IIb myofibers. We show that Tw2 expression maintains progenitor cells in an undifferentiated state that is poised to initiate myogenesis in response to appropriate cues that extinguish Tw2 expression. Tw2-expressing myogenic progenitors represent a previously unrecognized, fiber-type specific stem cell involved in post-natal muscle growth and regeneration.
Wear mechanisms in polyethylene components for total knee replacements are inherently mechanical; the local stresses or strains exceed some material limit. Retrieval analysis and knee simulators have provided the means to quantify the damage observed in vivo or in vitro. These results have been circumstantially linked to the material stresses obtained from computational simulations using finite element analysis, knee simulator tests, and computational simulations of two condylar knee designs. We hypothesize that if an equivalent loading environment is produced in the computational simulation, we can correlate the distribution of computed stresses with observed damage of simulator specimens and further relate design differences to in vivo performance from retrieval analyses. The finite element model agreed with the knee simulator kinematics and kinetics within 2-13%, and composite FEA contact areas matched 66-90% of the damage areas due to burnishing on the simulator specimens. Burnishing was the primary mode of damage for both the simulator and retrieval specimens corresponding with the relatively low magnitudes of contact stress observed. Both the computational and experimental techniques underpredicted the amount determined from retrieval analysis, but the differences between the two designs were consistent for all three methods. Combining these techniques strengthens the applicability of the computational simulation while highlighting the complementary approach of these methods for preclinical testing and assessing the link between material state and damage.
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