Generic placeholder image

Current Stem Cell Research & Therapy

Editor-in-Chief

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

Research Article

L-Carnitine Reduced Cellular Aging of Bone Marrow Resident C-Kit+ Hematopoietic Progenitor Cells Through Telomere Dependent Pathways

Author(s): Ezzatollah Fathi, Soheila Montazersaheb, Zohreh Sanaat, Ailar Nakhlband, Somayeh Vandghanooni, Raheleh Farahzadi* and Ilja Vietor*

Volume 18, Issue 2, 2023

Published on: 02 August, 2022

Page: [231 - 236] Pages: 6

DOI: 10.2174/1574888X17666220511141123

Price: $65

conference banner
Abstract

Background: Increased oxygen species levels can induce mitochondrial DNA damage and chromosomal aberrations and cause defective stem cell differentiation, leading finally to senescence of stem cells. In recent years, several studies have reported that antioxidants can improve stem cell survival and subsequently affect the potency and differentiation of these cells. Finding factors, which reduce the senescence tendency of stem cells upon expansion, has great potential for cellular therapy in regenerative medicine. This study aimed to evaluate the effects of L-carnitine (LC) on the aging of C-kit+ hematopoietic progenitor cells (HPCs) via examining the expression of some signaling pathway components.

Methods: For this purpose, bone marrow resident C-kit+ HPCs were enriched by the magnetic-activated cell sorting (MACS) method and were characterized using flow cytometry as well as immunocytochemistry. Cells were treated with LC, and at the end of the treatment period, the cells were subjected to the realtime PCR technique along with a western blotting assay for measurement of the telomere length and assessment of protein expression, respectively.

Results: The results showed that 0.2 mM LC caused the elongation of the telomere length and increased the TERT protein expression. In addition, a significant increase was observed in the protein expression of p38, p53, BCL2, and p16 as key components of the telomere-dependent pathway.

Conclusion: It can be concluded that LC can increase the telomere length as an effective factor in increasing the cell survival and maintenance of the C-kit+ HPCs via these signaling pathway components.

Keywords: Bone marrow resident C-kit+ hematopoietic stem cells, L-carnitine, telomere length, cell aging, signaling pathways, chromosomal aberrations.

Graphical Abstract
[1]
Bernitz JM, Kim HS, MacArthur B, Sieburg H, Moore K. Hematopoietic stem cells count and remember self-renewal divisions. Cell 2016; 167(5): 1296-1309.e10.
[http://dx.doi.org/10.1016/j.cell.2016.10.022] [PMID: 27839867]
[2]
Bryder D, Rossi DJ, Weissman IL. Hematopoietic stem cells: The paradigmatic tissue-specific stem cell. Am J Pathol 2006; 169(2): 338-46.
[http://dx.doi.org/10.2353/ajpath.2006.060312] [PMID: 16877336]
[3]
Flores I, Canela A, Vera E, Tejera A, Cotsarelis G, Blasco MA. The longest telomeres: A general signature of adult stem cell compartments. Genes Dev 2008; 22(5): 654-67.
[http://dx.doi.org/10.1101/gad.451008] [PMID: 18283121]
[4]
Fernández-Marcelo T, Sánchez-Pernaute A, Pascua I, et al. Clinical relevance of telomere status and telomerase activity in colorectal cancer. PLoS One 2016; 11(2): e0149626.
[http://dx.doi.org/10.1371/journal.pone.0149626] [PMID: 26913901]
[5]
Cao Y, Qu HJ, Li P, Wang CB, Wang LX, Han ZW. Single dose administration of L-carnitine improves antioxidant activities in healthy subjects. Tohoku J Exp Med 2011; 224(3): 209-13.
[http://dx.doi.org/10.1620/tjem.224.209] [PMID: 21701126]
[6]
Farahzadi R, Mesbah-Namin SA, Zarghami N, Fathi E. L-carnitine effectively induces hTERT gene expression of human adipose tissue-derived mesenchymal stem cells obtained from the aged subjects. Int J Stem Cells 2016; 9(1): 107-14.
[http://dx.doi.org/10.15283/ijsc.2016.9.1.107] [PMID: 27426092]
[7]
Mobarak H, Fathi E, Farahzadi R, Zarghami N, Javanmardi S. L-carnitine significantly decreased aging of rat adipose tissue-derived mesenchymal stem cells. Vet Res Commun 2017; 41(1): 41-7.
[http://dx.doi.org/10.1007/s11259-016-9670-9] [PMID: 27943151]
[8]
Farahzadi R, Fathi E, Mesbah-Namin SA, Zarghami N. Anti-aging protective effect of L-carnitine as clinical agent in regenerative medicine through increasing telomerase activity and change in the hTERT promoter CpG island methylation status of adipose tissue-derived mesenchymal stem cells. Tissue Cell 2018; 54: 105-13.
[http://dx.doi.org/10.1016/j.tice.2018.08.012] [PMID: 30309499]
[9]
Wynd S, Westaway M, Vohra S, Kawchuk G. Correction: Acetyl-L-carnitine in the treatment of peripheral neuropathic pain: A systematic review and meta-analysis of randomized controlled trials. PLoS One 2015; 10(6): e0129991.
[http://dx.doi.org/10.1371/journal.pone.0129991] [PMID: 26065423]
[10]
Bonavita E. Study of the efficacy and tolerability of L-acetylcarnitine therapy in the senile brain. Int J Clin Pharmacol Ther Toxicol 1986; 24(9): 511-6.
[PMID: 3781687]
[11]
Hollister L, Gruber N. Drug treatment of Alzheimer’s disease. Effects on caregiver burden and patient quality of life. Drugs Aging 1996; 8(1): 47-55.
[http://dx.doi.org/10.2165/00002512-199608010-00008] [PMID: 8785468]
[12]
Law SF, Fenton TR, Snyder FF, Fung E, Lewis V. Carnitine profile changes in pediatric hematopoietic stem cell transplant: New role for carnitine? J Pediatr Hematol Oncol 2020; 42(5): e321-7.
[http://dx.doi.org/10.1097/MPH.0000000000001723] [PMID: 32032238]
[13]
Fathi E, Farahzadi R, Valipour B. Alginate/gelatin encapsulation promotes NK cells differentiation potential of bone marrow resident C-kit+ hematopoietic stem cells. Int J Biol Macromol 2021; 177: 317-27.
[http://dx.doi.org/10.1016/j.ijbiomac.2021.02.131] [PMID: 33621568]
[14]
Fathi E, Farahzadi R, Javanmardi S, Vietor I. L-carnitine extends the telomere length of the cardiac differentiated CD117+- expressing stem cells. Tissue Cell 2020; 67: 101429.
[http://dx.doi.org/10.1016/j.tice.2020.101429] [PMID: 32861877]
[15]
Fathi E, Farahzadi R, Vietor I, Javanmardi S. Cardiac differentiation of bone-marrow-resident C-kit+ stem cells by L-carnitine increases through secretion of VEGF, IL6, IGF-1, and TGF- β as clinical agents in cardiac regeneration. J Biosci 2020; 45(1): 1-11.
[http://dx.doi.org/10.1007/s12038-020-00063-0] [PMID: 32713855]
[16]
O’Callaghan NJ, Fenech M. A quantitative PCR method for measuring absolute telomere length. Biol Proced Online 2011; 13(1): 3-12.
[http://dx.doi.org/10.1186/1480-9222-13-3] [PMID: 21369534]
[17]
Fathi E, Vietor I. Mesenchymal stem cells promote caspase expression in Molt-4 leukemia cells via GSK-3α/Β and ERK1/2 signaling pathways as a therapeutic strategy. Curr Gene Ther 2021; 21(1): 81-8.
[http://dx.doi.org/10.2174/1566523220666201005111126] [PMID: 33019931]
[18]
Singh AK, Althoff MJ, Cancelas JA. Signaling pathways regulating hematopoietic stem cell and progenitor aging. Curr Stem Cell Rep 2018; 4(2): 166-81.
[http://dx.doi.org/10.1007/s40778-018-0128-6] [PMID: 31453073]
[19]
Kasper G, Mao L, Geissler S, et al. Insights into mesenchymal stem cell aging: Involvement of antioxidant defense and actin cytoskeleton. Stem Cells 2009; 27(6): 1288-97.
[http://dx.doi.org/10.1002/stem.49] [PMID: 19492299]
[20]
Lenzi A, Sgrò P, Salacone P, et al. A placebo-controlled double-blind randomized trial of the use of combined l-carnitine and l-acetyl-carnitine treatment in men with asthenozoospermia. Fertil Steril 2004; 81(6): 1578-84.
[http://dx.doi.org/10.1016/j.fertnstert.2003.10.034] [PMID: 15193480]
[21]
Gülçin I. Antioxidant and antiradical activities of L-carnitine. Life Sci 2006; 78(8): 803-11.
[http://dx.doi.org/10.1016/j.lfs.2005.05.103] [PMID: 16253281]
[22]
Jang Y-Y, Sharkis SJ. A low level of reactive oxygen species selects for primitive hematopoietic stem cells that may reside in the low-oxygenic niche. Blood 2007; 110(8): 3056-63.
[http://dx.doi.org/10.1182/blood-2007-05-087759] [PMID: 17595331]
[23]
Dumble M, Moore L, Chambers SM, et al. The impact of altered p53 dosage on hematopoietic stem cell dynamics during aging. Blood 2007; 109(4): 1736-42.
[http://dx.doi.org/10.1182/blood-2006-03-010413] [PMID: 17032926]
[24]
Baker DJ, Childs BG, Durik M, et al. Naturally occurring p16(Ink4a)-positive cells shorten healthy lifespan. Nature 2016; 530(7589): 184-9.
[http://dx.doi.org/10.1038/nature16932] [PMID: 26840489]
[25]
Park IK, Qian D, Kiel M, et al. Bmi-1 is required for maintenance of adult self-renewing haematopoietic stem cells. Nature 2003; 423(6937): 302-5.
[http://dx.doi.org/10.1038/nature01587] [PMID: 12714971]

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