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| Research Progress on the Relationship Between Autophagy and Mesenchymal Stem Cell Senescence |
DENG Jia-qiang,LI Wei-yao,ZHONG Li-jun,YU Shu-min*( ) |
| College of Veterinary Medicine, Sichuan Agricultural University, Chengdu 611130, China |
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Abstract Mesenchymal stem cells (MSCs) have attracted great attention in regenerative medicine due to their capacities for multilineage differentiation, immunomodulation and migration. However, increased donor age and prolonged in vitro culture inevitably trigger senescence. MSC senescence and cellular dysfunction are considered one of the main causes of aging in an individual and the development of degenerative diseases, while they hinder the application of MSCs in regenerative medicine. As a major lysosome-dependent degradation and recycling pathway, autophagy is the mechanism through which the cytoplasmic components can be renewed, contributing to maintaining intracellular homeostasis and resisting environmental stress, and may become a potential therapeutic target for regulating MSC secescence. This review focuses on the phenotypic characterizations, functional alterations and molecular mechanisms in senescent MSCs, and the relationship between autophagy and senescence, which develop a theoretical foundation for the research and clinical application of MSCs.
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Received: 05 September 2021
Published: 07 April 2022
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Corresponding Authors:
Shu-min YU
E-mail: yayushumin@sicau.edu.cn
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| [1] |
Samsonraj R M, Raghunath M, Nurcombe V, et al. Concise review: multifaceted characterization of human mesenchymal stem cells for use in regenerative medicine. Stem Cells Translational Medicine, 2017, 6(12):2173-2185.
doi: 10.1002/sctm.17-0129
pmid: 29076267
|
|
|
| [2] |
Beerman I, Seita J, Inlay M, et al. Hematopoietic stem cell quiescence attenuates DNA damage repair and response contributing to age-dependent DNA damage accumulation. Experimental Hematology, 2014, 42(8):S24.
|
|
|
| [3] |
Ferro F, Spelat R, Shaw G, et al. Survival/adaptation of bone marrow-derived mesenchymal stem cells after long-term starvation through selective processes. Stem Cells (Dayton, Ohio), 2019, 37(6):813-827.
doi: 10.1002/stem.2998
|
|
|
| [4] |
Ceccariglia S, Cargnoni A, Silini A R, et al. Autophagy: a potential key contributor to the therapeutic action of mesenchymal stem cells. Autophagy, 2020, 16(1):28-37.
doi: 10.1080/15548627.2019.1630223
pmid: 31185790
|
|
|
| [5] |
Ho T T, Warr M R, Adelman E R, et al. Autophagy maintains the metabolism and function of young and old stem cells. Nature, 2017, 543(7644):205-210.
doi: 10.1038/nature21388
|
|
|
| [6] |
Hao H J, Chen G H, Liu J J, et al. Culturing on Wharton’s jelly extract delays mesenchymal stem cell senescence through p53 and p16INK4a/pRb pathways. PLoS One, 2013, 8(3):e58314.
doi: 10.1371/journal.pone.0058314
|
|
|
| [7] |
Pan X H, Chen Y H, Yang Y K, et al. Relationship between senescence in macaques and bone marrow mesenchymal stem cells and the molecular mechanism. Aging, 2019, 11(2):590-614.
doi: 10.18632/aging.v11i2
|
|
|
| [8] |
Wang D J, Jang D J. Protein kinase CK2 regulates cytoskeletal reorganization during ionizing radiation-induced senescence of human mesenchymal stem cells. Cancer Research, 2009, 69(20):8200-8207.
doi: 10.1158/0008-5472.CAN-09-1976
|
|
|
| [9] |
Yang Y H K, Ogando C R, See C W, et al. Changes in phenotype and differentiation potential of human mesenchymal stem cells aging in vitro. Stem Cell Research & Therapy, 2018, 9(1):131.
|
|
|
| [10] |
Carlessi L, De Filippis L, Lecis D, et al. DNA-damage response, survival and differentiation in vitro of a human neural stem cell line in relation to ATM expression. Cell Death & Differentiation, 2009, 16(6):795-806.
|
|
|
| [11] |
Minieri V, Saviozzi S, Gambarotta G, et al. Persistent DNA damage-induced premature senescence alters the functional features of human bone marrow mesenchymal stem cells. Journal of Cellular and Molecular Medicine, 2015, 19(4):734-743.
doi: 10.1111/jcmm.12387
|
|
|
| [12] |
Zhang H Y, Sun L L, Wang K, et al. Loss of H3K9me3 correlates with ATM activation and histone H2AX phosphorylation deficiencies in Hutchinson-Gilford progeria syndrome. PLoS One, 2016, 11(12):e0167454.
doi: 10.1371/journal.pone.0167454
|
|
|
| [13] |
Stab B R, Martinez L, Grismaldo A, et al. Mitochondrial functional changes characterization in young and senescent human adipose derived MSCs. Frontiers in Aging Neuroscience, 2016, 8:299.
|
|
|
| [14] |
Kim J, Ko J. A novel PPARγ2 modulator sLZIP controls the balance between adipogenesis and osteogenesis during mesenchymal stem cell differentiation. Cell Death & Differentiation, 2014, 21(10):1642-1655.
|
|
|
| [15] |
Lee J S, Lee J M, Im G I. Electroporation-mediated transfer of Runx2 and Osterix genes to enhance osteogenesis of adipose stem cells. Biomaterials, 2011, 32(3):760-768.
doi: 10.1016/j.biomaterials.2010.09.042
|
|
|
| [16] |
孙泽绪, 赵辰, 廖军义, 等. 抑制Runx2的表达增强BMP2诱导的干细胞成软骨分化. 中国生物工程杂志, 2016, 36(4):57-62.
|
|
|
| [16] |
Sun Z X, Zhao C, Liao J Y, et al. Suppression of Runx2 potentiates BMP2-induced chondrogenic differentiation. China Biotechnology, 2016, 36(4):57-62.
|
|
|
| [17] |
Geissler S, Textor M, Kühnisch J, et al. Functional comparison of chronological and in vitro aging: differential role of the cytoskeleton and mitochondria in mesenchymal stromal cells. PLoS One, 2012, 7(12):e52700.
doi: 10.1371/journal.pone.0052700
|
|
|
| [18] |
Choudhery M S, Badowski M, Muise A, et al. Donor age negatively impacts adipose tissue-derived mesenchymal stem cell expansion and differentiation. Journal of Translational Medicine, 2014, 12:8.
doi: 10.1186/1479-5876-12-8
pmid: 24397850
|
|
|
| [19] |
Liu M C, Lei H, Dong P, et al. Adipose-derived mesenchymal stem cells from the elderly exhibit decreased migration and differentiation abilities with senescent properties. Cell Transplantation, 2017, 26(9):1505-1519.
doi: 10.1177/0963689717721221
|
|
|
| [20] |
Khanh V C, Zulkifli A F, Tokunaga C, et al. Aging impairs beige adipocyte differentiation of mesenchymal stem cells via the reduced expression of Sirtuin 1. Biochemical and Biophysical Research Communications, 2018, 500(3):682-690.
doi: 10.1016/j.bbrc.2018.04.136
|
|
|
| [21] |
Cheng H C, Qiu L, Ma J, et al. Replicative senescence of human bone marrow and umbilical cord derived mesenchymal stem cells and their differentiation to adipocytes and osteoblasts. Molecular Biology Reports, 2011, 38(8):5161-5168.
doi: 10.1007/s11033-010-0665-2
|
|
|
| [22] |
常铖, 刘梦婷, 张权, 等. 长期传代培养人脐带间充质干细胞免疫调节功能的比较. 中国细胞生物学学报, 2020, 42(4):609-619.
|
|
|
| [22] |
Chang C, Liu M T, Zhang Q, et al. Comparison of immunomodulatory functions in human umbilical cord mesenchymal stem cells after long-term expansion. Chinese Journal of Cell Biology, 2020, 42(4):609-619.
|
|
|
| [23] |
李丹婷, 黄晓雅, 白利鹏, 等. IFN-γ对犬BMSCs增殖及分泌多种免疫抑制因子的影响. 中国免疫学杂志, 2019, 35(19):2326-2331.
|
|
|
| [23] |
Li D T, Huang X Y, Bai L P, et al. Effect of IFN-γon proliferation and secretion of various immunosuppressive factors in canine BMSCs. Chinese Journal of Immunology, 2019, 35(19):2326-2331.
|
|
|
| [24] |
Yu K R, Lee J Y, Kim H S, et al. A p38 MAPK-mediated alteration of COX-2/PGE2 regulates immunomodulatory properties in human mesenchymal stem cell aging. PLoS One, 2014, 9(8):e102426.
doi: 10.1371/journal.pone.0102426
|
|
|
| [25] |
Lee J Y, Yu K R, Kim H S, et al. BMI1 inhibits senescence and enhances the immunomodulatory properties of human mesenchymal stem cells via the direct suppression of MKP-1/DUSP1. Aging (Albany NY), 2016, 8(8):1670-1689.
|
|
|
| [26] |
Sepúlveda J C, Tomé M, Fernández M E, et al. Cell senescence abrogates the therapeutic potential of human mesenchymal stem cells in the lethal endotoxemia model. Stem Cells (Dayton, Ohio), 2014, 32(7):1865-1877.
doi: 10.1002/stem.1654
|
|
|
| [27] |
Rombouts W J C, Ploemacher R E. Primary murine MSC show highly efficient homing to the bone marrow but lose homing ability following culture. Leukemia, 2003, 17(1):160-170.
pmid: 12529674
|
|
|
| [28] |
Tang D D, Gerlach B D. The roles and regulation of the actin cytoskeleton, intermediate filaments and microtubules in smooth muscle cell migration. Respiratory Research, 2017, 18(1):54.
doi: 10.1186/s12931-017-0544-7
|
|
|
| [29] |
Jung E M, Kwon O, Kwon K S, et al. Evidences for correlation between the reduced VCAM-1 expression and hyaluronan synthesis during cellular senescence of human mesenchymal stem cells. Biochemical and Biophysical Research Communications, 2011, 404(1):463-469.
doi: 10.1016/j.bbrc.2010.12.003
pmid: 21144825
|
|
|
| [30] |
Jakovljevic J, Harrell C R, Fellabaum C, et al. Modulation of autophagy as new approach in mesenchymal stem cell-based therapy. Biomedicine & Pharmacotherapy, 2018, 104:404-410.
doi: 10.1016/j.biopha.2018.05.061
|
|
|
| [31] |
Ma Y, Qi M, An Y, et al. Autophagy controls mesenchymal stem cell properties and senescence during bone aging. Aging Cell, 2018, 17(1):e12709.
doi: 10.1111/acel.2018.17.issue-1
|
|
|
| [32] |
Wan Y X, Zhuo N Q, Li Y L, et al. Autophagy promotes osteogenic differentiation of human bone marrow mesenchymal stem cell derived from osteoporotic vertebrae. Biochemical and Biophysical Research Communications, 2017, 488(1):46-52.
doi: 10.1016/j.bbrc.2017.05.004
|
|
|
| [33] |
Beaupere C, Garcia M, Larghero J, et al. The HIV proteins Tat and Nef promote human bone marrow mesenchymal stem cell senescence and alter osteoblastic differentiation. Aging Cell, 2015, 14(4):534-546.
doi: 10.1111/acel.12308
pmid: 25847297
|
|
|
| [34] |
Liu Z Z, Hong C G, Hu W B, et al. Autophagy receptor OPTN (optineurin) regulates mesenchymal stem cell fate and bone-fat balance during aging by clearing FABP3. Autophagy, 2021, 17(10):2766-2782.
doi: 10.1080/15548627.2020.1839286
|
|
|
| [35] |
Yang M, Wen T, Chen H X, et al. Knockdown of insulin-like growth factor 1 exerts a protective effect on hypoxic injury of aged BM-MSCs: role of autophagy. Stem Cell Research & Therapy, 2018, 9(1):284.
|
|
|
| [36] |
Zhang Y L, Zhu W W, He H W, et al. Macrophage migration inhibitory factor rejuvenates aged human mesenchymal stem cells and improves myocardial repair. Aging (Albany NY), 2019, 11(24):12641-12660.
|
|
|
| [37] |
Zhang D Y, Chen Y F, Xu X B, et al. Autophagy inhibits the mesenchymal stem cell aging induced by D-galactose through ROS/JNK/p38 signalling. Clinical and Experimental Pharmacology & Physiology, 2020, 47(3):466-477.
|
|
|
| [38] |
Kheirandish M, Gavgani S P, Samiee S. The effect of hypoxia preconditioning on the neural and stemness genes expression profiling in human umbilical cord blood mesenchymal stem cells. Transfusion and Apheresis Science, 2017, 56(3):392-399.
doi: S1473-0502(17)30056-3
pmid: 28428031
|
|
|
| [39] |
Kim C, Park J M, Song Y, et al. HIF1α-mediated AIMP3 suppression delays stem cell aging via the induction of autophagy. Aging Cell, 2019, 18(2):e12909.
doi: 10.1111/acel.12909
|
|
|
| [40] |
Capasso S, Alessio N, Squillaro T, et al. Changes in autophagy, proteasome activity and metabolism to determine a specific signature for acute and chronic senescent mesenchymal stromal cells. Oncotarget, 2015, 6(37):39457-39468.
doi: 10.18632/oncotarget.v6i37
|
|
|
| [41] |
Zheng Y, Hu C J, Zhuo R H, et al. Inhibition of autophagy alleviates the senescent state of rat mesenchymal stem cells during long-term culture. Molecular Medicine Reports, 2014, 10(6):3003-3008.
doi: 10.3892/mmr.2014.2624
pmid: 25310478
|
|
|
| [42] |
Zheng Y, Lei Y S, Hu C H, et al. P53 regulates autophagic activity in senescent rat mesenchymal stromal cells. Experimental Gerontology, 2016, 75:64-71.
doi: 10.1016/j.exger.2016.01.004
pmid: 26792455
|
|
|
| [43] |
Chang T C, Hsu M F, Wu K K. High glucose induces bone marrow-derived mesenchymal stem cell senescence by upregulating autophagy. PLoS One, 2015, 10(5):e0126537.
doi: 10.1371/journal.pone.0126537
|
|
|
| [44] |
Yun S P, Han Y S, Lee J H, et al. Melatonin rescues mesenchymal stem cells from senescence induced by the uremic toxin p-cresol via inhibiting mTOR-dependent autophagy. Biomolecules & Therapeutics, 2018, 26(4):389-398.
|
|
|
| [45] |
Zhang M Y, Du Y, Lu R Z, et al. Cholesterol retards senescence in bone marrow mesenchymal stem cells by modulating autophagy and ROS/p53/p21Cip1/Waf1 pathway. Oxidative Medicine and Cellular Longevity, 2016, 2016:7524308.
|
|
|
| [46] |
Molaei S, Roudkenar M H, Amiri F, et al. Down-regulation of the autophagy gene, ATG7, protects bone marrow-derived mesenchymal stem cells from stressful conditions. Blood Research, 2015, 50(2):80-86.
doi: 10.5045/br.2015.50.2.80
|
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