Pax7+ Satellite Cells in Human Skeletal Muscle After Exercise: A Systematic Review and Meta-analysis

Abstract

Background: Skeletal muscle has extraordinary regenerative capabilities against challenge, mainly owing to its resident muscle stem cells, commonly identified by Pax7⁺, which expediently donate nuclei to the regenerating multinucleated myofibers. This local reserve of stem cells in damaged muscle tissues is replenished by undifferentiated bone marrow stem cells (CD34⁺) permeating into the surrounding vascular system.

Objective: The purpose of the study was to provide a quantitative estimate for the changes in Pax7⁺ muscle stem cells (satellite cells) in humans following an acute bout of exercise until 96 h, in temporal relation to circulating CD34⁺ bone marrow stem cells. A subgroup analysis of age was also performed.

Methods: Four databases (Web of Science, PubMed, Scopus, and BASE) were used for the literature search until February 2022. Pax7⁺ cells in human skeletal muscle were the primary outcome. Circulating CD34⁺ cells were the secondary outcome. The standardized mean difference (SMD) was calculated using a random-effects meta-analysis. Subgroup analyses were conducted to examine the influence of age, training status, type of exercise, and follow-up time after exercise.

Results: The final search identified 20 studies for Pax7⁺ cells comprising a total of 370 participants between the average age of 21 and 74 years and 26 studies for circulating CD34⁺ bone marrow stem cells comprising 494 participants between the average age of 21 and 67 years. Only one study assessed Pax7⁺ cells immediately after aerobic exercise and showed a 32% reduction in exercising muscle followed by a fast repletion to pre-exercise level within 3 h. A large effect on increasing Pax7⁺ cell content in skeletal muscles was observed 24 h after resistance exercise (SMD = 0.89, p < 0.001). Pax7⁺ cells increased to ~ 50% above pre-exercise level 24-72 h after resistance exercise. For a subgroup analysis of age, a large effect (SMD = 0.81, p < 0.001) was observed on increasing Pax7⁺ cells in exercised muscle among adults aged > 50 years, whereas adults at younger age presented a medium effect (SMD = 0.64, p < 0.001). Both resistance exercise and aerobic exercise showed a medium overall effect in increasing circulating CD34⁺ cells (SMD = 0.53, p < 0.001), which declined quickly to the pre-exercise baseline level after exercise within 6 h.

Conclusions: An immediate depletion of Pax7⁺ cells in exercising skeletal muscle concurrent with a transient release of CD34⁺ cells suggest a replenishment of the local stem cell reserve from bone marrow. A protracted Pax7⁺ cell expansion in the muscle can be observed during 24-72 h after resistance exercise. This result provides a scientific basis for exercise recommendations on weekly cycles allowing for adequate recovery time. Exercise-induced Pax7⁺ cell expansion in muscle remains significant at higher age, despite a lower stem cell reserve after age 50 years. More studies are required to confirm whether Pax7⁺ cell increment can occur after aerobic exercise.

Clinical trial registration: Registered at the International Prospective Register of Systematic Reviews (PROSPERO) [identification code CRD42021265457].