Generic placeholder image

Current Stem Cell Research & Therapy

Editor-in-Chief

ISSN (Print): 1574-888X
ISSN (Online): 2212-3946

Research Article

Bone Marrow Mesenchymal Stem Cells Derived from Juvenile Macaques Reversed the Serum Protein Expression Profile in Aged Macaques

Author(s): Qianqian Yu, Chuan Tian, Guanke Lv, Qingpeng Kong, Gonghua Li, Guangxu Zhu, Xiangqing Zhu* and Xinghua Pan*

Volume 18, Issue 3, 2023

Published on: 22 August, 2022

Page: [391 - 400] Pages: 10

DOI: 10.2174/1574888X17666220429111218

Price: $65

conference banner
Abstract

Objective: The aim of the study was to reveal the changes in serum protein composition and content in macaques during the process of ageing, and explore the effect of bone marrow mesenchymal stem cell (BMMSC) on the serum protein expression profile in elderly macaques.

Methods: Naturally ageing macaques were assessed according to age. BMMSCs were intravenously infused into aged macaques. In addition, peripheral blood was collected to obtain serum for dataindependent acquisition (DIA) protein sequencing to identify aging-related indicators. One hundred eighty days after macaques received BMMSC treatment, haemoxylin and eosin (HE) staining was performed to observe the morphology and structure of aortic arches.

Results: Compared to infant and young control macaques, aged macaques showed erythema on the face, dry skin, reduced amounts of hair on the head and back, and paleness. Cultured BMMSCs from the 4th passage (P4 BMMSCs) were grown in accordance with standards used to culture mesenchymal stem cells. After BMMSC treatment, the assessed aortic arches showed no calcium salt deposition or cell necrosis, and the characteristics of the serum protein expression profile tended to be similar to that of the infant and young groups, with the expression of 41 proteins upregulated with age and that of 30 proteins downregulated with age but upregulated after BMMSC treatment. Moreover, we identified 44 significantly differentially expressed proteins between the aged model and treatment groups; 11 of the upregulated proteins were related to vascular ageing, neuronal ageing and haematopoiesis, and 33 of the downregulated proteins were associated with neuronal ageing, cardiovascular disease, and tumours. Interestingly, S100 expression in serum was significantly decreased, COMP expression was significantly increased, NKAP expression reappeared, and LCN2, CSF1R, CORO1C, CSTB and RSU-1 expression disappeared after BMMSC treatment.

Conclusion: BMMSCs can reverse ageing-related serum protein expression.

Keywords: Bone marrow mesenchymal stem cells, ageing, serum proteins, ageing-related indicators, tumours, juvenile macaques.

[1]
Uyar B, Palmer D, Kowald A, et al. Single-cell analyses of aging, inflammation and senescence. Ageing Res Rev 2020; 64: 101156.
[http://dx.doi.org/10.1016/j.arr.2020.101156] [PMID: 32949770]
[2]
Chen C, Zhou M, Ge Y, Wang X. SIRT1 and aging related signaling pathways. Mech Ageing Dev 2020; 187: 111215.
[http://dx.doi.org/10.1016/j.mad.2020.111215] [PMID: 32084459]
[3]
Galkin F, Mamoshina P, Aliper A, de Magalhães JP, Gladyshev VN, Zhavoronkov A. Biohorology and biomarkers of aging: Current state-of-the-art, challenges and opportunities. Ageing Res Rev 2020; 60: 101050.
[http://dx.doi.org/10.1016/j.arr.2020.101050] [PMID: 32272169]
[4]
Hamrick MW, Stranahan AM. Metabolic regulation of aging and age-related disease. Ageing Res Rev 2020; 64: 101175.
[http://dx.doi.org/10.1016/j.arr.2020.101175] [PMID: 32971259]
[5]
Santoro A, Martucci M, Conte M, Capri M, Franceschi C, Salvioli S. Inflammaging, hormesis and the rationale for anti-aging strategies. Ageing Res Rev 2020; 64: 101142.
[http://dx.doi.org/10.1016/j.arr.2020.101142] [PMID: 32814129]
[6]
Das G, Paramithiotis S, Sundaram Sivamaruthi B, et al. Traditional fermented foods with anti-aging effect: A concentric review. Food Res Int 2020; 134: 109269.
[http://dx.doi.org/10.1016/j.foodres.2020.109269] [PMID: 32517898]
[7]
Zhao J, Lan X, Liu Y, et al. Anti-aging role of Chinese herbel medicine: An overview of scientific evidence from 2008 to 2018. Ann Palliat Med 2020; 9(3): 1230-48.
[http://dx.doi.org/10.21037/apm.2020.04.09] [PMID: 32389009]
[8]
Dhalaria R, Verma R, Kumar D, et al. Bioactive compounds of edible fruits with their anti-aging properties: A comprehensive review to prolong human life. Antioxidants 2020; 9(11): 11.
[http://dx.doi.org/10.3390/antiox9111123] [PMID: 33202871]
[9]
Al-Azab M, Wang B, Elkhider A, et al. Indian hedgehog regulates senescence in bone marrow-derived mesenchymal stem cell through modulation of ROS/mTOR/4EBP1, p70S6K1/2 pathway. Aging (Albany NY) 2020; 12(7): 5693-715.
[http://dx.doi.org/10.18632/aging.102958] [PMID: 32235006]
[10]
Ha DH, Kim HK, Lee J, et al. Mesenchymal stem/stromal cell-derived exosomes for immunomodulatory therapeutics and skin regeneration. Cells 2020; 9(5): 5.
[http://dx.doi.org/10.3390/cells9051157] [PMID: 32392899]
[11]
Ohta H, Liu X, Maeda M. Autologous adipose mesenchymal stem cell administration in arteriosclerosis and potential for anti-aging application: A retrospective cohort study. Stem Cell Res Ther 2020; 11(1): 538.
[http://dx.doi.org/10.1186/s13287-020-02067-x] [PMID: 33308301]
[12]
Lei Q, Gao F, Liu T, et al. Extracellular vesicles deposit PCNA to rejuvenate aged bone marrow-derived mesenchymal stem cells and slow age-related degeneration. Sci Transl Med 2021; 13(578): 578.
[http://dx.doi.org/10.1126/scitranslmed.aaz8697] [PMID: 33504653]
[13]
Nanzadsuren T, Myatav T, Dorjkhuu A, Byamba K. Association between serum melatonin and skin aging in an urban population of Mongolia. J Cosmet Dermatol 2020; 19(6): 1501-7.
[http://dx.doi.org/10.1111/jocd.13166] [PMID: 31566872]
[14]
Serum Methylmalonic Acid Mediates Aging-Related Cancer Aggressiveness. Cancer Discov 2020; 10: 1441.
[15]
Eum JY, Lee JC, Yi SS, Kim IY, Seong JK, Moon MH. Aging-related lipidomic changes in mouse serum, kidney, and heart by nanoflow ultrahigh-performance liquid chromatography-tandem mass spectrometry. J Chromatogr A 2020; 1618: 460849.
[http://dx.doi.org/10.1016/j.chroma.2020.460849] [PMID: 31928769]
[16]
Kawarazaki W, Mizuno R, Nishimoto M, et al. Salt causes aging-associated hypertension via vascular Wnt5a under Klotho deficiency. J Clin Invest 2020; 130(8): 4152-66.
[http://dx.doi.org/10.1172/JCI134431] [PMID: 32597829]
[17]
Zhang F, Ge W, Ruan G, Cai X, Guo T. Data-independent acquisition mass spectrometry-based proteomics and software tools: A glimpse in 2020. Proteomics 2020; 20(17-18): e1900276.
[http://dx.doi.org/10.1002/pmic.201900276] [PMID: 32275110]
[18]
Fernández-Costa C, Martínez-Bartolomé S, McClatchy DB, Saviola AJ, Yu NK, Yates JR III. Impact of the identification strategy on the reproducibility of the DDA and DIA results. J Proteome Res 2020; 19(8): 3153-61.
[http://dx.doi.org/10.1021/acs.jproteome.0c00153] [PMID: 32510229]
[19]
Arju G, Taivosalo A, Pismennoi D, et al. Application of the UHPLC-DIA-HRMS Method for Determination of Cheese Peptides. Foods 2020; 9(8): 8.
[http://dx.doi.org/10.3390/foods9080979] [PMID: 32718013]
[20]
Li KW, Gonzalez-Lozano MA, Koopmans F, Smit AB. Recent developments in data independent acquisition (DIA) mass spectrometry: Application of quantitative analysis of the brain proteome. Front Mol Neurosci 2020; 13: 564446.
[http://dx.doi.org/10.3389/fnmol.2020.564446] [PMID: 33424549]
[21]
Pan XH, Chen YH, Yang YK, et al. Relationship between senescence in macaques and bone marrow mesenchymal stem cells and the molecular mechanism. Aging (Albany NY) 2019; 11(2): 590-614.
[http://dx.doi.org/10.18632/aging.101762] [PMID: 30673631]
[22]
Pan XH, Zhang XJ, Yao X, et al. Effects and mechanisms of mUCMSCs on ovarian structure and function in naturally ageing C57 mice. J Ovarian Res 2021; 14(1): 133.
[http://dx.doi.org/10.1186/s13048-021-00854-5] [PMID: 34645513]
[23]
Guo DB, Zhu XQ, Li QQ, et al. Efficacy and mechanisms underlying the effects of allogeneic umbilical cord mesenchymal stem cell transplantation on acute radiation injury in tree shrews. Cytotechnology 2018; 70(5): 1447-68.
[http://dx.doi.org/10.1007/s10616-018-0239-z] [PMID: 30066056]
[24]
Demirci S, Zeng J, Wu Y, et al. BCL11A enhancer-edited hematopoietic stem cells persist in rhesus monkeys without toxicity. J Clin Invest 2020; 130(12): 6677-87.
[http://dx.doi.org/10.1172/JCI140189] [PMID: 32897878]
[25]
Li ZH, He XP, Li H, He RQ, Hu XT. Age-associated changes in amyloid-β and formaldehyde concentrations in cerebrospinal fluid of rhesus monkeys. Zool Res 2020; 41(4): 444-8.
[http://dx.doi.org/10.24272/j.issn.2095-8137.2020.088] [PMID: 32543791]
[26]
Yang YK, Li Y, Wang YY, et al. The effects of BMMSC treatment on lung tissue degeneration in elderly macaques. Stem Cell Res Ther 2021; 12(1): 156.
[http://dx.doi.org/10.1186/s13287-021-02201-3] [PMID: 33648583]
[27]
Tian C, He J, An Y, et al. Bone marrow mesenchymal stem cells derived from juvenile macaques reversed ovarian ageing in elderly macaques. Stem Cell Res Ther 2021; 12(1): 460.
[http://dx.doi.org/10.1186/s13287-021-02486-4] [PMID: 34407863]
[28]
Gonzalez LL, Garrie K, Turner MD. Role of S100 proteins in health and disease. Biochim Biophys Acta Mol Cell Res 2020; 1867(6): 118677.
[http://dx.doi.org/10.1016/j.bbamcr.2020.118677] [PMID: 32057918]
[29]
Zhao J, Ding Y, He R, et al. Dose-effect relationship and molecular mechanism by which BMSC-derived exosomes promote peripheral nerve regeneration after crush injury. Stem Cell Res Ther 2020; 11(1): 360.
[http://dx.doi.org/10.1186/s13287-020-01872-8] [PMID: 32811548]
[30]
Wu L, Han D, Jiang J, et al. Co-transplantation of bone marrow mesenchymal stem cells and monocytes in the brain stem to repair the facial nerve axotomy. Eur J Histochem 2020; 64(s2): s2.
[http://dx.doi.org/10.4081/ejh.2020.3136] [PMID: 32705858]
[31]
Zhong Z, Chen A, Fa Z, et al. Bone marrow mesenchymal stem cells upregulate PI3K/AKT pathway and down-regulate NF-κB pathway by secreting glial cell-derived neurotrophic factors to regulate microglial polarization and alleviate differentiation pain in rats. Neurobiol Dis 2020; 143: 104945.
[http://dx.doi.org/10.1016/j.nbd.2020.104945] [PMID: 32428552]
[32]
Li C, Wang N, Schäffer AA, et al. Mutations in COMP cause familial carpal tunnel syndrome. Nat Commun 2020; 11(1): 3642.
[http://dx.doi.org/10.1038/s41467-020-17378-z] [PMID: 32686688]
[33]
Caron MMJ, Janssen MPF, Peeters L, et al. Aggrecan and COMP improve periosteal chondrogenesis by delaying chondrocyte hypertrophic maturation. Front Bioeng Biotechnol 2020; 8: 1036.
[http://dx.doi.org/10.3389/fbioe.2020.01036] [PMID: 32984292]
[34]
Shibata K, Sato K, Shirai R, et al. Lipocalin-2 exerts pro-atherosclerotic effects as evidenced by in vitro and in vivo experiments. Heart Vessels 2020; 35(7): 1012-24.
[http://dx.doi.org/10.1007/s00380-020-01556-6] [PMID: 31960147]
[35]
Liu HY, Yu LF, Zhou TG, et al. Lipopolysaccharide-stimulated bone marrow mesenchymal stem cells-derived exosomes inhibit H2O2-induced cardiomyocyte inflammation and oxidative stress via regulating miR-181a-5p/ATF2 axis. Eur Rev Med Pharmacol Sci 2020; 24(19): 10069-77.
[PMID: 33090414]
[36]
Sharma S, Pandey NN, Sinha M, et al. Randomized, double-blind, placebo-controlled trial to evaluate safety and therapeutic efficacy of angiogenesis induced by intraarterial autologous bone marrow-derived stem cells in patients with severe peripheral Arterial Disease. J Vasc Interv Radiol 2021; 32(2): 157-63.
[http://dx.doi.org/10.1016/j.jvir.2020.09.003] [PMID: 33248918]
[37]
Ma Q, Hou L, Gao X, Yan K. NKAP promotes renal cell carcinoma growth via AKT/mTOR signalling pathway. Cell Biochem Funct 2020; 38(5): 574-81.
[http://dx.doi.org/10.1002/cbf.3508] [PMID: 32032976]
[38]
Fukuda E, Tanaka H, Yamaguchi K, et al. Identification and characterization of the antigen recognized by the germ cell mAb TRA98 using a human comprehensive wet protein array. Genes Cells 2021; 26(3): 180-9.
[http://dx.doi.org/10.1111/gtc.12832] [PMID: 33527666]
[39]
Yun J, Yang H, Li X, et al. Up-regulation of miR-297 mediates aluminum oxide nanoparticle-induced lung inflammation through activation of Notch pathway. Environ Pollut 2020; 259: 113839.
[http://dx.doi.org/10.1016/j.envpol.2019.113839] [PMID: 31918133]
[40]
Li J, Li Z, Wang C, et al. The regulatory effect of VEGF-ax on rat bone marrow mesenchymal stem cells’ angioblastic differentiation and its proangiogenic ability. Stem Cells Dev 2020; 29(10): 667-77.
[http://dx.doi.org/10.1089/scd.2019.0198] [PMID: 32079499]
[41]
Hagan N, Kane JL, Grover D, et al. CSF1R signaling is a regulator of pathogenesis in progressive MS. Cell Death Dis 2020; 11(10): 904.
[http://dx.doi.org/10.1038/s41419-020-03084-7] [PMID: 33097690]
[42]
Lonardi S, Scutera S, Licini S, et al. CSF1R is required for differentiation and migration of langerhans cells and langerhans cell histiocytosis. Cancer Immunol Res 2020; 8(6): 829-41.
[http://dx.doi.org/10.1158/2326-6066.CIR-19-0232] [PMID: 32238382]
[43]
Han S, Ding X, Wang S, Xu L, Li W, Sun W. miR-133a-3p regulates hepatocellular carcinoma progression through targeting CORO1C. Cancer Manag Res 2020; 12: 8685-93.
[http://dx.doi.org/10.2147/CMAR.S254617] [PMID: 33061567]
[44]
Zhang W, Song C, Ren X. Circ_0003998 regulates the progression and docetaxel sensitivity of DTX-resistant non-small cell lung cancer cells by the miR-136-5p/CORO1C Axis. Technol Cancer Res Treat 2021; 20: 1533033821990040.
[http://dx.doi.org/10.1177/1533033821990040] [PMID: 33511909]
[45]
Yuan B, El Dana F, Ly S, et al. Bone marrow stromal cells induce an ALDH+ stem cell-like phenotype and enhance therapy resistance in AML through a TGF-β-p38-ALDH2 pathway. PLoS One 2020; 15(11): e0242809.
[http://dx.doi.org/10.1371/journal.pone.0242809] [PMID: 33253299]
[46]
Guan W, Wang X, Lin Q, Zhang J, Ren W, Xu G. Transforming growth factor β/miR 143 3p/cystatin B axis is a therapeutic target in human ovarian cancer. Int J Oncol 2019; 55(1): 267-76.
[http://dx.doi.org/10.3892/ijo.2019.4815] [PMID: 31180557]
[47]
Penna E, Cerciello A, Chambery A, et al. Cystatin B involvement in synapse physiology of rodent brains and human cerebral organoids. Front Mol Neurosci 2019; 12: 195.
[http://dx.doi.org/10.3389/fnmol.2019.00195] [PMID: 31467503]

Rights & Permissions Print Cite
© 2024 Bentham Science Publishers | Privacy Policy