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.
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.
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.
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.
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.
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Moss FP, Leblond CP. Satellite cells as the source of nuclei in muscles of growing rats. Anat Rec. 1971;170(4):421–35. https://doi.org/10.1002/ar.1091700405.
Schmalbruch H. The morphology of regeneration of skeletal muscles in the rat. Tissue Cell. 1976;8(4):673–92. https://doi.org/10.1016/0040-8166(76)90039-2.
Bischoff R. Proliferation of muscle satellite cells on intact myofibers in culture. Dev Biol. 1986;115(1):129–39. https://doi.org/10.1016/0012-1606(86)90234-4.
Nederveen JP, Joanisse S, Séguin CM, Bell KE, Baker SK, Phillips SM, et al. The effect of exercise mode on the acute response of satellite cells in old men. Acta Physiol (Oxf). 2015;215(4):177–90. https://doi.org/10.1111/apha.12601.
Cadot B, Gache V, Gomes ER. Moving and positioning the nucleus in skeletal muscle: one step at a time. Nucleus. 2015;6(5):373–81. https://doi.org/10.1080/19491034.2015.1090073.
Egner IM, Bruusgaard JC, Gundersen K. Satellite cell depletion prevents fiber hypertrophy in skeletal muscle. Development. 2016;143(16):2898–906. https://doi.org/10.1242/dev.134411.
Dreyer HC, Blanco CE, Sattler FR, Schroeder ET, Wiswell RA. Satellite cell numbers in young and older men 24 hours after eccentric exercise. Muscle Nerve. 2006;33(2):242–53. https://doi.org/10.1002/mus.20461.
Snijders T, Verdijk LB, Smeets JS, McKay BR, Senden JM, Hartgens F, et al. The skeletal muscle satellite cell response to a single bout of resistance-type exercise is delayed with aging in men. Age (Dordr). 2014;36(4):9699. https://doi.org/10.1007/s11357-014-9699-z.
Seale P, Sabourin LA, Girgis-Gabardo A, Mansouri A, Gruss P, Rudnicki MA. Pax7 is required for the specification of myogenic satellite cells. Cell. 2000;102(6):777–86. https://doi.org/10.1016/s0092-8674(00)00066-0.
Chargé SB, Rudnicki MA. Cellular and molecular regulation of muscle regeneration. Physiol Rev. 2004;84(1):209–38. https://doi.org/10.1152/physrev.00019.2003.
Relaix F, Montarras D, Zaffran S, Gayraud-Morel B, Rocancourt D, Tajbakhsh S, et al. Pax3 and Pax7 have distinct and overlapping functions in adult muscle progenitor cells. J Cell Biol. 2006;172(1):91–102. https://doi.org/10.1083/jcb.200508044.
Bellamy LM, Joanisse S, Grubb A, Mitchell CJ, McKay BR, Phillips SM, et al. The acute satellite cell response and skeletal muscle hypertrophy following resistance training. PLoS ONE. 2014;9(10): e109739. https://doi.org/10.1371/journal.pone.0109739.
Farup J, Rahbek SK, Knudsen IS, de Paoli F, Mackey AL, Vissing K. Whey protein supplementation accelerates satellite cell proliferation during recovery from eccentric exercise. Amino Acids. 2014;46(11):2503–16. https://doi.org/10.1007/s00726-014-1810-3.
Hyldahl RD, Olson T, Welling T, Groscost L, Parcell AC. Satellite cell activity is differentially affected by contraction mode in human muscle following a work-matched bout of exercise. Front Physiol. 2014;5:485. https://doi.org/10.3389/fphys.2014.00485.
Nederveen JP, Joanisse S, Snijders T, Ivankovic V, Baker SK, Phillips SM, et al. Skeletal muscle satellite cells are located at a closer proximity to capillaries in healthy young compared with older men. J Cachexia Sarcopenia Muscle. 2016;7(5):547–54. https://doi.org/10.1002/jcsm.12105.
Snijders T, Nederveen JP, McKay BR, Joanisse S, Verdijk LB, van Loon LJ, et al. Satellite cells in human skeletal muscle plasticity. Front Physiol. 2015;6:283. https://doi.org/10.3389/fphys.2015.00283.
Welle S, Totterman S, Thornton C. Effect of age on muscle hypertrophy induced by resistance training. J Gerontol A Biol Sci Med Sci. 1996;51(6):M270–5. https://doi.org/10.1093/gerona/51a.6.m270.
Verdijk LB, Snijders T, Drost M, Delhaas T, Kadi F, Van Loon LJC. Satellite cells in human skeletal muscle; from birth to old age. Age. 2014;36(2):545–57. https://doi.org/10.1007/s11357-013-9583-2.
Walker DK, Fry CS, Drummond MJ, Dickinson JM, Timmerman KL, Gundermann DM, et al. Pax7+ satellite cells in young and older adults following resistance exercise. Muscle Nerve. 2012;46(1):51–9. https://doi.org/10.1002/mus.23266.
Joanisse S, McKay BR, Nederveen JP, Scribbans TD, Gurd BJ, Gillen JB, et al. Satellite cell activity, without expansion, after nonhypertrophic stimuli. Am J Physiol Regul Integr and Comp Physiol. 2015;309(9):R1101–11. https://doi.org/10.1152/ajpregu.00249.2015.
Corbel SY, Lee A, Yi L, Duenas J, Brazelton TR, Blau HM, et al. Contribution of hematopoietic stem cells to skeletal muscle. Nat Med. 2003;9(12):1528–32. https://doi.org/10.1038/nm959.
Ferrari G, Cusella-De Angelis G, Coletta M, Paolucci E, Stornaiuolo A, Cossu G, et al. Muscle regeneration by bone marrow-derived myogenic progenitors. Science. 1998;279(5356):1528–30. https://doi.org/10.1126/science.279.5356.1528.
Bittner RE, Schöfer C, Weipoltshammer K, Ivanova S, Streubel B, Hauser E, et al. Recruitment of bone-marrow-derived cells by skeletal and cardiac muscle in adult dystrophic mdx mice. Anat Embryol (Berl). 1999;199(5):391–6. https://doi.org/10.1007/s004290050237.
Tamaki T, Okada Y, Uchiyama Y, Tono K, Masuda M, Nitta M, et al. Skeletal muscle-derived CD34+/45- and CD34-/45- stem cells are situated hierarchically upstream of Pax7+ cells. Stem Cells Dev. 2008;17(4):653–67. https://doi.org/10.1089/scd.2008.0070.
Camargo FD, Green R, Capetenaki Y, Jackson KA, Goodell MA. Single hematopoietic stem cells generate skeletal muscle through myeloid intermediates. Nat Med. 2003;9(12):1520–7. https://doi.org/10.1038/nm963.
Krause DS, Ito T, Fackler MJ, Smith OM, Collector MI, Sharkis SJ, et al. Characterization of murine CD34, a marker for hematopoietic progenitor and stem cells. Blood. 1994;84(3):691–701.
Montarras D, Morgan J, Collins C, Relaix F, Zaffran S, Cumano A, et al. Direct isolation of satellite cells for skeletal muscle regeneration. Science. 2005;309(5743):2064–7. https://doi.org/10.1126/science.1114758.
Ieronimakis N, Balasundaram G, Rainey S, Srirangam K, Yablonka-Reuveni Z, Reyes M. Absence of CD34 on murine skeletal muscle satellite cells marks a reversible state of activation during acute injury. PLoS ONE. 2010;5(6): e10920. https://doi.org/10.1371/journal.pone.0010920.
Fina L, Molgaard HV, Robertson D, Bradley NJ, Monaghan P, Delia D, et al. Expression of the CD34 gene in vascular endothelial cells. Blood. 1990;75(12):2417–26. https://doi.org/10.1002/eji.1830250606.
Lee JY, Qu-Petersen Z, Cao B, Kimura S, Jankowski R, Cummins J, et al. Clonal isolation of muscle-derived cells capable of enhancing muscle regeneration and bone healing. J Cell Biol. 2000;150(5):1085–100. https://doi.org/10.1083/jcb.150.5.1085.
Beauchamp JR, Heslop L, Yu DS, Tajbakhsh S, Kelly RG, Wernig A, et al. Expression of CD34 and Myf5 defines the majority of quiescent adult skeletal muscle satellite cells. J Cell Biol. 2000;151(6):1221–34. https://doi.org/10.1083/jcb.151.6.1221.
Tamaki T, Akatsuka A, Ando K, Nakamura Y, Matsuzawa H, Hotta T, et al. Identification of myogenic-endothelial progenitor cells in the interstitial spaces of skeletal muscle. J Cell Biol. 2002;157(4):571–7. https://doi.org/10.1083/jcb.200112106.
Lee TXY, Wu J, Jean WH, Condello G, Alkhatib A, Hsieh CC, et al. Reduced stem cell aging in exercised human skeletal muscle is enhanced by ginsenoside Rg1. Aging (Albany NY). 2021;13(12):16567–76. https://doi.org/10.18632/aging.203176.
Yang C, Jiao Y, Wei B, Yang Z, Wu JF, Jensen J, et al. Aged cells in human skeletal muscle after resistance exercise. Aging (Albany NY). 2018;10(6):1356–65. https://doi.org/10.18632/aging.101472.
Page MJ, McKenzie JE, Bossuyt PM, Boutron I, Hoffmann TC, Mulrow CD, et al. The PRISMA 2020 statement: an updated guideline for reporting systematic reviews. BMJ. 2021;372: n71. https://doi.org/10.1136/bmj.n71.
Brown P, Brunnhuber K, Chalkidou K, Chalmers I, Clarke M, Fenton M, et al. How to formulate research recommendations. BMJ. 2006;333(7572):804–6. https://doi.org/10.1136/bmj.38987.492014.94.
PeÑAilillo L, Blazevich A, Numazawa H, Nosaka K. Metabolic and muscle damage profiles of concentric versus repeated eccentric cycling. Med Sci Sports Exerc. 2013;45(9):1173–81. https://doi.org/10.1249/MSS.0b013e31828f8a73.
van de Vyver M, Myburgh KH. Cytokine and satellite cell responses to muscle damage: interpretation and possible confounding factors in human studies. J Muscle Res Cell Motil. 2012;33(3–4):177–85. https://doi.org/10.1007/s10974-012-9303-z.
Moreau D, Chou E. The acute effect of high-intensity exercise on executive function: a meta-analysis. Perspect Psychol Sci. 2019;14(5):734–64. https://doi.org/10.1177/1745691619850568.
Garber CE, Blissmer B, Deschenes MR, Franklin BA, Lamonte MJ, Lee IM, et al. Quantity and quality of exercise for developing and maintaining cardiorespiratory, musculoskeletal, and neuromotor fitness in apparently healthy adults: guidance for prescribing exercise. Med Sci Sports Exerc. 2011;43(7):1334–59. https://doi.org/10.1249/MSS.0b013e318213fefb.
Scribbans TD, Vecsey S, Hankinson PB, Foster WS, Gurd BJ. The effect of training intensity on VO2max in young healthy adults: a meta-regression and meta-analysis. Int J Exerc Sci. 2016;9(2):230–47.
De Pauw K, Roelands B, Cheung SS, de Geus B, Rietjens G, Meeusen R. Guidelines to classify subject groups in sport-science research. Int J Sports Physiol Perform. 2013;8(2):111–22. https://doi.org/10.1123/ijspp.8.2.111.
Sterne JAC, Savović J, Page MJ, Elbers RG, Blencowe NS, Boutron I, et al. RoB 2: a revised tool for assessing risk of bias in randomised trials. BMJ. 2019;366: l4898. https://doi.org/10.1136/bmj.l4898.
JPT H, Jagoe T, J C, M C, T L, MJ P, et al. Cochrane handbook for systematic reviews of interventions version 6.3 (updated February 2022); 2022.
Fritz CO, Morris PE, Richler JJ. Effect size estimates: current use, calculations, and interpretation. J Exp Psychol Gen. 2012;141(1):2–18. https://doi.org/10.1037/a0024338.
Lamberink HJ, Otte WM, Sinke MRT, Lakens D, Glasziou PP, Tijdink JK, et al. Statistical power of clinical trials increased while effect size remained stable: an empirical analysis of 136,212 clinical trials between 1975 and 2014. J Clin Epidemiol. 2018;102:123–8. https://doi.org/10.1016/j.jclinepi.2018.06.014.
Faraone SV. Interpreting estimates of treatment effects: implications for managed care. P T. 2008;33(12):700–11.
Lee DK. Alternatives to P value: confidence interval and effect size. Korean J Anesthesiol. 2016;69(6):555–62. https://doi.org/10.4097/kjae.2016.69.6.555.
Hoaglin DC. Misunderstandings about Q and “Cochran’s Q test” in meta-analysis. Stat Med. 2016;35(4):485–95. https://doi.org/10.1002/sim.6632.
Higgins JP, Thompson SG, Deeks JJ, Altman DG. Measuring inconsistency in meta-analyses. BMJ. 2003;327(7414):557–60. https://doi.org/10.1136/bmj.327.7414.557.
Aguayo D, Mueller SM, Boutellier U, Auer M, Jung HH, Flück M, et al. One bout of vibration exercise with vascular occlusion activates satellite cells. Exp Physiol. 2016;101(2):295–307. https://doi.org/10.1113/EP085330.
Abou Sawan S, Hodson N, Babits P, Malowany JM, Kumbhare D, Moore DR. Satellite cell and myonuclear accretion is related to training-induced skeletal muscle fiber hypertrophy in young males and females. J Appl Physiol (1985). 2021;131(3):871–80. https://doi.org/10.1152/japplphysiol.00424.2021.
Roberts LA, Raastad T, Markworth JF, Figueiredo VC, Egner IM, Shield A, et al. Post-exercise cold water immersion attenuates acute anabolic signalling and long-term adaptations in muscle to strength training. J Physiol. 2015;593(18):4285–301. https://doi.org/10.1113/jp270570.
Baker JM, Nederveen JP, Parise G. Aerobic exercise in humans mobilizes HSCs in an intensity-dependent manner. J Appl Physiol (1985). 2017;122(1):182–90. https://doi.org/10.1152/japplphysiol.00696.2016.
Bonsignore MR, Morici G, Riccioni R, Huertas A, Petrucci E, Veca M, et al. Hemopoietic and angiogenetic progenitors in healthy athletes: different responses to endurance and maximal exercise. J Appl Physiol (1985). 2010;109(1):60–7. https://doi.org/10.1152/japplphysiol.01344.2009.
Bonsignore MR, Morici G, Santoro A, Pagano M, Cascio L, Bonanno A, et al. Circulating hematopoietic progenitor cells in runners. J Appl Physiol (1985). 2002;93(5):1691–7. https://doi.org/10.1152/japplphysiol.00376.2002.
Nederveen JP, Snijders T, Joanisse S, Wavell CG, Mitchell CJ, Johnston LM, et al. Altered muscle satellite cell activation following 16 wk of resistance training in young men. Am J Physiol Regul Integr Comp Physiol. 2017;312(1):R85-92. https://doi.org/10.1152/ajpregu.00221.2016.
O’Carroll L, Wardrop B, Murphy RP, Ross MD, Harrison M. Circulating angiogenic cell response to sprint interval and continuous exercise. Eur J Appl Physiol. 2019;119(3):743–52. https://doi.org/10.1007/s00421-018-04065-7.
Niemiro GM, Parel J, Beals J, van Vliet S, Paluska SA, Moore DR, et al. Kinetics of circulating progenitor cell mobilization during submaximal exercise. J Appl Physiol (1985). 2017;122(3):675–82. https://doi.org/10.1152/japplphysiol.00936.2016.
Ribeiro F, Ribeiro IP, Gonçalves AC, Alves AJ, Melo E, Fernandes R, et al. Effects of resistance exercise on endothelial progenitor cell mobilization in women. Sci Rep. 2017;7(1):17880. https://doi.org/10.1038/s41598-017-18156-6.
Chang E, Paterno J, Duscher D, Maan ZN, Chen JS, Januszyk M, et al. Exercise induces stromal cell-derived factor-1α-mediated release of endothelial progenitor cells with increased vasculogenic function. Plast Reconstr Surg. 2015;135(2):340e-e350. https://doi.org/10.1097/PRS.0000000000000917.
Thijssen DHJ, Vos JB, Verseyden C, Van Zonneveld AJ, Smits P, Sweep FCGJ, et al. Haematopoietic stem cells and endothelial progenitor cells in healthy men: effect of aging and training. Aging Cell. 2006;5(6):495–503. https://doi.org/10.1111/j.1474-9726.2006.00242.x.
Wu J, Saovieng S, Cheng IS, Jensen J, Jean W-H, Alkhatib A, et al. Satellite cells depletion in exercising human skeletal muscle is restored by ginseng component Rg1 supplementation. J Funct Foods. 2019;58:27–33. https://doi.org/10.1016/j.jff.2019.04.032.
Nederveen JP, Joanisse S, Thomas AC, Snijders T, Manta K, Bell KE, et al. Age-related changes to the satellite cell niche are associated with reduced activation following exercise. FASEB J. 2020;34(7):8975–89. https://doi.org/10.1096/fj.201900787R.
Toth KG, McKay BR, De Lisio M, Little JP, Tarnopolsky MA, Parise G. IL-6 induced STAT3 signalling is associated with the proliferation of human muscle satellite cells following acute muscle damage. PLoS ONE. 2011;6(3): e17392. https://doi.org/10.1371/journal.pone.0017392.
Mackey AL, Rasmussen LK, Kadi F, Schjerling P, Helmark IC, Ponsot E, et al. Activation of satellite cells and the regeneration of human skeletal muscle are expedited by ingestion of nonsteroidal anti-inflammatory medication. FASEB J. 2016;30(6):2266–81. https://doi.org/10.1096/fj.201500198R.
Nederveen JP, Joanisse S, Snijders T, Thomas ACQ, Kumbhare D, Parise G. The influence of capillarization on satellite cell pool expansion and activation following exercise-induced muscle damage in healthy young men. J Physiol. 2018;596(6):1063–78. https://doi.org/10.1113/JP275155.
Shill DD, Lansford KA, Hempel HK, Call JA, Murrow JR, Jenkins NT. Effect of exercise intensity on circulating microparticles in men and women. Exp Physiol. 2018;103(5):693–700. https://doi.org/10.1113/EP086644.
Ross M, Ingram L, Taylor G, Malone E, Simpson RJ, West D, et al. Older men display elevated levels of senescence-associated exercise-responsive CD28null angiogenic T cells compared with younger men. Physiol Rep. 2018;6(12): e13697. https://doi.org/10.14814/phy2.13697.
Lee HS, Muthalib M, Akimoto T, Nosaka K. Changes in the number of circulating CD34+ cells after eccentric exercise of the elbow flexors in relation to muscle damage. J Sport Health Sci. 2015;4(3):275–81. https://doi.org/10.1016/j.jshs.2013.12.005.
Craenenbroeck EMFV, Vrints CJ, Haine SE, Vermeulen K, Goovaerts I, Van Tendeloo VFI, et al. A maximal exercise bout increases the number of circulating CD34+/KDR+ endothelial progenitor cells in healthy subjects: relation with lipid profile. J Appl Physiol (1985). 2008;104(4):1006–13. https://doi.org/10.1152/japplphysiol.01210.2007.
Zaldivar F, Eliakim A, Radom-Aizik S, Leu S-Y, Cooper DM. The effect of brief exercise on circulating CD34+ stem cells in early and late pubertal boys. Pediatr Res. 2007;61(4):491–5. https://doi.org/10.1203/pdr.0b013e3180332d36.
McKay BR, Ogborn DI, Baker JM, Toth KG, Tarnopolsky MA, Parise G. Elevated SOCS3 and altered IL-6 signaling is associated with age-related human muscle stem cell dysfunction. Am J Physiol Cell Physiol. 2013;304(8):C717–28. https://doi.org/10.1152/ajpcell.00305.2012.
Snijders T, Bell KE, Nederveen JP, Saddler NI, Mazara N, Kumbhare DA, et al. Ingestion of a multi-ingredient supplement does not alter exercise-induced satellite cell responses in older men. J Nutr. 2018;148(6):891–9. https://doi.org/10.1093/jn/nxy063.
Möbius-Winkler S, Hilberg T, Menzel K, Golla E, Burman A, Schuler G, et al. Time-dependent mobilization of circulating progenitor cells during strenuous exercise in healthy individuals. J Appl Physiol (1985). 2009;107(6):1943–50. https://doi.org/10.1152/japplphysiol.00532.2009.
McKay BR, Ogborn DI, Bellamy LM, Tarnopolsky MA, Parise G. Myostatin is associated with age-related human muscle stem cell dysfunction. FASEB J. 2012;26(6):2509–21. https://doi.org/10.1096/fj.11-198663.
Cermak NM, Snijders T, McKay BR, Parise G, Verdijk LB, Tarnopolsky MA, et al. Eccentric exercise increases satellite cell content in type II muscle fibers. Med Sci Sports Exerc. 2013;45(2):230–7. https://doi.org/10.1249/MSS.0b013e318272cf47.
Agha NH, Baker FL, Kunz HE, Graff R, Azadan R, Dolan C, et al. Vigorous exercise mobilizes CD34+ hematopoietic stem cells to peripheral blood via the β(2)-adrenergic receptor. Brain Behav Immun. 2018;68:66–75. https://doi.org/10.1016/j.bbi.2017.10.001.
Harris E, Rakobowchuk M, Birch KM. Interval exercise increases angiogenic cell function in postmenopausal women. BMJ Open Sport Exerc Med. 2017;3(1): e000248. https://doi.org/10.1136/bmjsem-2017-000248.
Morici G, Zangla D, Santoro A, Pelosi E, Petrucci E, Gioia M, et al. Supramaximal exercise mobilizes hematopoietic progenitors and reticulocytes in athletes. Am J Physiol Regul Integr Comp Physiol. 2005;289(5):R1496–503. https://doi.org/10.1152/ajpregu.00338.2005.
Kroepfl JM, Pekovits K, Stelzer I, Fuchs R, Zelzer S, Hofmann P, et al. Exercise increases the frequency of circulating hematopoietic progenitor cells, but reduces hematopoietic colony-forming capacity. Stem Cells Dev. 2012;21(16):2915–25. https://doi.org/10.1089/scd.2012.0017.
Krüger K, Pilat C, Schild M, Lindner N, Frech T, Muders K, et al. Progenitor cell mobilization after exercise is related to systemic levels of G-CSF and muscle damage. Scand J Med Sci Sports. 2015;25(3):e283–91. https://doi.org/10.1111/sms.12320.
Laufs U, Urhausen A, Werner N, Scharhag J, Heitz A, Kissner G, et al. Running exercise of different duration and intensity: effect on endothelial progenitor cells in healthy subjects. Eur J Cardiovasc Prev Rehabil. 2005;12(4):407–14. https://doi.org/10.1097/01.hjr.0000174823.87269.2e.
Ross MD, Wekesa AL, Phelan JP, Harrison M. Resistance exercise increases endothelial progenitor cells and angiogenic factors. Med Sci Sports Exerc. 2013;46(1):16–23. https://doi.org/10.1249/MSS.0b013e3182a142da.
Yang Z, Wang JM, Chen L, Luo CF, Tang AL, Tao J. Acute exercise-induced nitric oxide production contributes to upregulation of circulating endothelial progenitor cells in healthy subjects. J Hum Hypertens. 2007;21(6):452–60. https://doi.org/10.1038/sj.jhh.1002171.
Montgomery R, Paterson A, Williamson C, Florida-James G, Ross MD. Blood flow restriction exercise attenuates the exercise-induced endothelial progenitor cell response in healthy, young men. Front Physiol. 2019;10:447. https://doi.org/10.3389/fphys.2019.00447.
Stelzer I, Kröpfl JM, Fuchs R, Pekovits K, Mangge H, Raggam RB, et al. Ultra-endurance exercise induces stress and inflammation and affects circulating hematopoietic progenitor cell function. Scand J Med Sci Sports. 2015;25(5):e442–50. https://doi.org/10.1111/sms.12347.
Wardyn GG, Rennard SI, Brusnahan SK, McGuire TR, Carlson ML, Smith LM, et al. Effects of exercise on hematological parameters, circulating side population cells, and cytokines. Exp Hematol. 2008;36(2):216–23. https://doi.org/10.1016/j.exphem.2007.10.003.
Kröpfl JM, Beltrami FG, Gruber HJ, Stelzer I, Spengler CM. Exercise-induced circulating hematopoietic stem and progenitor cells in well-trained subjects. Front Physiol. 2020;11:308. https://doi.org/10.3389/fphys.2020.00308.
Snijders T, Nederveen JP, Bell KE, Lau SW, Mazara N, Kumbhare DA, et al. Prolonged exercise training improves the acute type II muscle fibre satellite cell response in healthy older men. J Physiol. 2019;597(1):105–19. https://doi.org/10.1113/jp276260.
Reidy PT, Fry CS, Dickinson JM, Drummond MJ, Rasmussen BB. Postexercise essential amino acid supplementation amplifies skeletal muscle satellite cell proliferation in older men 24 hours postexercise. Physiol Rep. 2017;5(11): e13269. https://doi.org/10.14814/phy2.13269.
Snijders T, Verdijk LB, McKay BR, Smeets JS, van Kranenburg J, Groen BB, et al. Acute dietary protein intake restriction is associated with changes in myostatin expression after a single bout of resistance exercise in healthy young men. J Nutr. 2014;144(2):137–45. https://doi.org/10.3945/jn.113.183996.
Ross MD, Malone EM, Simpson R, Cranston I, Ingram L, Wright GP, et al. Lower resting and exercise-induced circulating angiogenic progenitors and angiogenic T cells in older men. Am J Physiol Heart Circ Physiol. 2018;314(3):H392-402. https://doi.org/10.1152/ajpheart.00592.2017.
Dreyfus PA, Chretien F, Chazaud B, Kirova Y, Caramelle P, Garcia L, et al. Adult bone marrow-derived stem cells in muscle connective tissue and satellite cell niches. Am J Pathol. 2004;164(3):773–9. https://doi.org/10.1016/S0002-9440(10)63165-3.
Zheng B, Cao B, Crisan M, Sun B, Li G, Logar A, et al. Prospective identification of myogenic endothelial cells in human skeletal muscle. Nat Biotechnol. 2007;25(9):1025–34. https://doi.org/10.1038/nbt1334.
Carlson BM, Faulkner JA. Muscle transplantation between young and old rats: age of host determines recovery. Am J Physiol Cell Physiol. 1989;256:C1262–6. https://doi.org/10.1152/ajpcell.1989.256.6.C1262.
Conboy IM, Conboy MJ, Smythe GM, Rando TA. Notch-mediated restoration of regenerative potential to aged muscle. Science. 2003;302:1575–7. https://doi.org/10.1126/science.1087573.
Rader EP, Faulkner JA. Effect of aging on the recovery following contraction-induced injury in muscles of female mice. J Appl Physiol (1985). 2006;101(3):887–92. https://doi.org/10.1152/japplphysiol.00380.2006.
Kadi F, Charifi N, Denis C, Lexell J. Satellite cells and myonuclei in young and elderly women and men. Muscle Nerve. 2004;29(1):120–7. https://doi.org/10.1002/mus.10510.
McKay BR, Toth KG, Tarnopolsky MA, Parise G. Satellite cell number and cell cycle kinetics in response to acute myotrauma in humans: immunohistochemistry versus flow cytometry. J Physiol. 2010;588(17):3307–20. https://doi.org/10.1113/jphysiol.2010.190876.
Decaroli MC, Rochira V. Aging and sex hormones in males. Virulence. 2017;8(5):545–70. https://doi.org/10.1080/21505594.2016.1259053.
Dechenes CJ, Verchere CB, Andrikopoulos S, Kahn SE. Human aging is associated with parallel reductions in insulin and amylin release. Am J Physiol Cell Physiol. 1998;275(5):E785–91. https://doi.org/10.1152/ajpendo.1998.275.5.E785.
Guillet C, Prod’homme M, Balage M, Gachon P, Giraudet C, Morin L, et al. Impaired anabolic response of muscle protein synthesis is associated with S6K1 dysregulation in elderly humans. FASEB J. 2004;18(13):1586–7. https://doi.org/10.1096/fj.03-1341fje.
Kimball SR, Horetsky RL, Jefferson LS. Signal transduction pathways involved in the regulation of protein synthesis by insulin in L6 myoblasts. Am J Physiol Cell Physiol. 1998;274(1):C221–8. https://doi.org/10.1152/ajpcell.1998.274.1.C221.
Kimball SR, Jurasinski CV, Lawrence JC Jr, Jefferson LS. Insulin stimulates protein synthesis in skeletal muscle by enhancing the association of eIF-4E and eIF-4G. Am J Physiol Cell Physiol. 1997;272:C754–9. https://doi.org/10.1152/ajpcell.1997.272.2.C754.
O’Connor PM, Kimball SR, Suryawan A, Bush JA, Nguyen HV, Jefferson LS, et al. Regulation of translation initiation by insulin and amino acids in skeletal muscle of neonatal pigs. Am J Physiol Cell Physiol. 2003;285(1):E40-53. https://doi.org/10.1152/ajpendo.00563.2002.
Perfetti R, Rafizadeh CM, Liotta AS, Egan JM. Age-dependent reduction in insulin secretion and insulin mRNA in isolated islets from rats. Am J Physiol Cell Physiol. 1995;269:E983–90. https://doi.org/10.1152/ajpendo.1995.269.6.E983.
Calvanese V, Lee LK, Mikkola HK. Sex hormone drives blood stem cell reproduction. EMBO J. 2014;33(6):534–5. https://doi.org/10.1002/embj.201487976.
Shahbazi M, Cundiff P, Zhou W, Lee P, Patel A, D’Souza SL, et al. The role of insulin as a key regulator of seeding, proliferation, and mRNA transcription of human pluripotent stem cells. Stem Cell Res Ther. 2019;10(1):228. https://doi.org/10.1186/s13287-019-1319-5.
Fu X, Xiao J, Wei Y, Li S, Liu Y, Yin J, et al. Combination of inflammation-related cytokines promotes long-term muscle stem cell expansion. Cell Res. 2015;25(6):655–73. https://doi.org/10.1038/cr.2015.58.
Wu J, Saovieng S, Cheng IS, Liu T, Hong S, Lin C-Y, et al. Ginsenoside Rg1 supplementation clears senescence-associated β-galactosidase in exercising human skeletal muscle. J Ginseng Res. 2019;43(4):580–8. https://doi.org/10.1016/j.jgr.2018.06.002.
Townsend JR, Stout JR, Jajtner AR, Church DD, Beyer KS, Riffe JJ, et al. Polyphenol supplementation alters intramuscular apoptotic signaling following acute resistance exercise. Physiol Rep. 2018;6(2): e13552. https://doi.org/10.14814/phy2.13552.
Justice JN, Gregory H, Tchkonia T, LeBrasseur NK, Kirkland JL, Kritchevsky SB, et al. Cellular senescence biomarker p16INK4a+ cell burden in thigh adipose is associated with poor physical function in older women. J Gerontol A Biol Sci Med Sci. 2018;73(7):939–45. https://doi.org/10.1093/gerona/glx134.
Forcina L, Cosentino M, Musarò A. Mechanisms regulating muscle regeneration: insights into the interrelated and time-dependent phases of tissue healing. Cells. 2020;9(5):1297. https://doi.org/10.3390/cells9051297.
Tidball JG. Regulation of muscle growth and regeneration by the immune system. Nat Rev Immunol. 2017;17(3):165–78. https://doi.org/10.1038/nri.2016.150.
Callegari GA, Novaes JS, Neto GR, Dias I, Garrido ND, Dani C. Creatine kinase and lactate dehydrogenase responses after different resistance and aerobic exercise protocols. J Hum Kinet. 2017;58:65–72. https://doi.org/10.1515/hukin-2017-0071.
Tufvesson E, Svensson H, Ankerst J, Bjermer L. Increase of club cell (Clara) protein (CC16) in plasma and urine after exercise challenge in asthmatics and healthy controls, and correlations to exhaled breath temperature and exhaled nitric oxide. Respir Med. 2013;107(11):1675–81. https://doi.org/10.1016/j.rmed.2013.08.004.
Bolger C, Tufvesson E, Anderson SD, Devereux G, Ayres JG, Bjermer L, et al. Effect of inspired air conditions on exercise-induced bronchoconstriction and urinary CC16 levels in athletes. J Appl Physiol (1985). 2011;111(4):1059–65. https://doi.org/10.1152/japplphysiol.00113.2011.
Combes A, Dekerle J, Dumont X, Twomey R, Bernard A, Daussin F, et al. Continuous exercise induces airway epithelium damage while a matched-intensity and volume intermittent exercise does not. Respir Res. 2019;20(1):12. https://doi.org/10.1186/s12931-019-0978-1.
Rochefort GY, Vaudin P, Bonnet N, Pages JC, Domenech J, Charbord P, et al. Influence of hypoxia on the domiciliation of mesenchymal stem cells after infusion into rats: possibilities of targeting pulmonary artery remodeling via cells therapies? Respir Res. 2005;6(1):125. https://doi.org/10.1186/1465-9921-6-125.
Rawlins EL, Hogan BL. Ciliated epithelial cell lifespan in the mouse trachea and lung. Am J Physiol Lung Cell Mol Physiol. 2008;295(1):L231–4. https://doi.org/10.1152/ajplung.90209.2008.
Welch C, Greig C, Masud T, Wilson D, Jackson TA. COVID-19 and acute sarcopenia. Aging Dis. 2020;11(6):1345–51. https://doi.org/10.14336/AD.2020.1014.
Steffl M, Bohannon RW, Petr M, Kohlikova E, Holmerova I. Relation between cigarette smoking and sarcopenia: meta-analysis. Physiol Res. 2015;64(3):419–26. https://doi.org/10.33549/physiolres.932802.
Collins CA, Olsen I, Zammit PS, Heslop L, Petrie A, Partridge TA, et al. Stem cell function, self-renewal, and behavioral heterogeneity of cells from the adult muscle satellite cell niche. Cell. 2005;122(2):289–301. https://doi.org/10.1016/j.cell.2005.05.010.
Sacco A, Doyonnas R, Kraft P, Vitorovic S, Blau HM. Self-renewal and expansion of single transplanted muscle stem cells. Nature. 2008;456(7221):502–6. https://doi.org/10.1038/nature07384.
Pesce M, Orlandi A, Iachininoto MG, Straino S, Torella AR, Rizzuti V, et al. Myoendothelial differentiation of human umbilical cord blood-derived stem cells in ischemic limb tissues. Circ Res. 2003;93(5):e51-62. https://doi.org/10.1161/01.Res.0000090624.04507.45.
Adams GR, Zaldivar FP, Nance DM, Kodesh E, Radom-Aizik S, Cooper DM. Exercise and leukocyte interchange among central circulation, lung, spleen, and muscle. Brain Behav Immun. 2011;25(4):658–66. https://doi.org/10.1016/j.bbi.2011.01.002.
Koç ON, Gerson SL, Phillips GL, Cooper BW, Kutteh L, Van Zant G, et al. Autologous CD34+ cell transplantation for patients with advanced lymphoma: effects of overnight storage on peripheral blood progenitor cell enrichment and engraftment. Bone Marrow Transplant. 1998;21(4):337–43. https://doi.org/10.1038/sj.bmt.1701096.
Frangoul H, Altshuler D, Cappellini MD, Chen YS, Domm J, Eustace BK, et al. CRISPR-Cas9 gene editing for sickle cell disease and β-thalassemia. N Engl J Med. 2021;384(3):252–60. https://doi.org/10.1056/NEJMoa2031054.
Hoggatt J, Singh P, Sampath J, Pelus LM. Prostaglandin E2 enhances hematopoietic stem cell homing, survival, and proliferation. Blood. 2009;113(22):5444–55. https://doi.org/10.1182/blood-2009-01-201335.
Sapp RM, Evans WS, Eagan LE, Chesney CA, Zietowski EM, Prior SJ, et al. The effects of moderate and high-intensity exercise on circulating markers of endothelial integrity and activation in young, healthy men. J Appl Physiol (1985). 2019;127(5):1245–56. https://doi.org/10.1152/japplphysiol.00477.2019.
No source of funding was used to assist in the preparation of this work.
Conflicts of interest/competing interests
Luthfia Dewi, Yin-Chou Lin, Andrew Nicholls, Giancarlo Condello, Chih-Yang Huang, and Chia-Hua Kuo have no conflicts of interest that are directly relevant to the content of this article.
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The datasets created and analyzed in this study are available from the corresponding author on reasonable request.
LD and CHK formulated the review. LD and CYH conducted database searches independently. LYC checked the references. LD, CYH, and CHK took part in the screening process and data extraction. LD performed the meta-analyses. LD, LYC, and CHK wrote the first draft on the manuscript. All authors critically revised the manuscript and approved the final version of the manuscript.
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Dewi, L., Lin, YC., Nicholls, A. et al. Pax7+ Satellite Cells in Human Skeletal Muscle After Exercise: A Systematic Review and Meta-analysis. Sports Med 53, 457–480 (2023). https://doi.org/10.1007/s40279-022-01767-z