Stimulating effect of nanocurcumin and crocin on proliferation and pluripotency of bone marrow-derived mesenchymal stem cells

Document Type : Original Article

Authors

1 Department of Immunology, Faculty of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran

2 Immunology Research Center, Mashhad University of Medical Sciences, Mashhad, Iran

3 Neuroscience Research Center, Mashhad University of Medical Sciences, Mashhad, Iran

4 Department of Biology, Mashhad Branch, Islamic Azad University, Mashhad, Iran

10.22038/ijbms.2024.74397.16197

Abstract

Objective(s): Enhancement of proliferation, pluripotency, and self-renewal capacity as the unique features of MSCs can improve their therapeutic potential to regenerate tissues. In this context, crocin and curcumin, carotenoid compounds with outstanding medicinal properties, could be promising for cell protection and growth. This study aimed to evaluate the impact of nanocurcumin and crocin on BM-MSCs proliferation and pluripotency in vitro.
Materials and Methods: BM-MSC were isolated from the iliac crest of SCI patients who were candidates for stem cell therapy. The effect of crocin and nanocurcumin on MSC proliferation was evaluated using MTT and PDT assay. The percentage of apoptotic MSCs was measured by flow cytometry. Furthermore, mRNA and protein expression of OCT4 and SOX2 as the proliferation and self-renewal related genes were quantified by real-time PCR and western blotting, respectively.
Results: Our findings demonstrated that only low concentrations of nanocurcumin (0.3 and 0.7  µM) and crocin (2.5 5 µM) significantly affected MSCs proliferation and protected them from apoptosis. Also, crocin and nanocurcumin at low doses caused an elevation in the mRNA and protein expression levels of OCT4 and SOX2 genes. In contrast, high concentrations decreased the survival of MSCs and led to increased apoptosis compared with the untreated group.
Conclusion: Our results suggest that using nanocurcumin and crocin separately in culturing MSCs can be considered proliferative agents to prepare the more advantageous tool for cell therapies. However, more in vitro and preclinical research is needed in this area.

Keywords

Main Subjects

References

1. Vasanthan J, Gurusamy N, Rajasingh S, Sigamani V, Kirankumar S, Thomas EL, et al. Role of human mesenchymal stem cells in regenerative therapy. Cells 2021; 10: 1-14.
2. Farkhad NK, Mahmoudi A, Mahdipour E. How similar are human mesenchymal stem cells derived from different origins? a review of comparative studies. Curr Stem Cell Res Ther 2021; 16: 980-993.
3. Babu S, Krishnan M, Panneerselvam A, Chinnaiyan M. A comprehensive review on therapeutic application of mesenchymal stem cells in neuroregeneration. Life Sci 2023; 327: 1-4.
4. Biglari N, Mehdizadeh A, Mastanabad MV, Gharaeikhezri MH, Afrakoti LGMP, Pourbala H, et al. Application of mesenchymal stem cells (MSCs) in neurodegenerative disorders: history, findings, and prospective challenges. Pathol Res Pract 2023; 247: 1-13.
5. Chu D-T, Phuong TNT, Tien NLB, Tran DK, Thanh VV, Quang TL, et al. An update on the progress of isolation, culture, storage, and clinical application of human bone marrow mesenchymal stem/stromal cells. Int J Mol Sci 2020; 21: 1-27.
6. Saud B, Malla R, Shrestha K. A review on the effect of plant extract on mesenchymal stem cell proliferation and differentiation. Stem Cells Int 2019; 2019: 1-13.
7. Milani A, Basirnejad M, Shahbazi S, Bolhassani A. Carotenoids: biochemistry, pharmacology and treatment. Br J Pharmacol; 2017: 174: 1290-1324.
8. Urošević M, Nikolić L, Gajić I, Nikolić V, Dinić A, Miljković V. Curcumin: Biological activities and modern pharmaceutical forms. Antibiotics (Basel) 2022; 11: 1-27.
9. Shah M, Murad W, Mubin S, Ullah O, Rehman NU, Rahman MH. Multiple health benefits of curcumin and its therapeutic potential. Environ Sci Pollut Res Int 2022; 29: 43732-43744.
10. Sharifi S, Zununi Vahed S, Ahmadian E, Maleki Dizaj S, Abedi A, Hosseiniyan Khatibi SM, et al. Stem cell therapy: Curcumin does the trick. Phytother Res; 33: 2927-2937.
11. Kabir M, Rahman M, Akter R, Behl T, Kaushik D, Mittal V, et al. Potential role of curcumin and its nanoformulations to treat various types of cancers. Biomolecules 2021; 11: 1-40.
12. Heidari S, Mahdiani S, Hashemi M, Kalalinia F. Recent advances in neurogenic and neuroprotective effects of curcumin through the induction of neural stem cells. Biotechnol Appl Biochem 2020; 67: 430-441.
13. Wang H, Zhou Y, Sun Q, Zhou C, Hu S, Lenahan C, et al. Update on nanoparticle-based drug delivery system for anti-inflammatory treatment. Front Bioeng Biotechnol 2021; 9: 1-9.
14. Hatamipour M, Sahebkar A, Alavizadeh SH, Dorri M, Jaafari MR. Novel nanomicelle formulation to enhance bioavailability and stability of curcuminoids. Iran J Basic Med Sci 2019; 22: 282-289.
15. Na Q, Xiyou D, Ji J, Zhai G. A review of stimuli-responsive polymeric micelles for tumor-targeted delivery of curcumin. Drug Dev Ind Pharm 2021; 47: 839-856.
16. Trigo-Gutierrez JK, Vega-Chacón Y, Soares AB, Mima EGdO. Antimicrobial activity of curcumin in nanoformulations: a comprehensive review. Int J Mol Sci 2021; 22: 1-49.
17. Song Y-n, Wang Y, Zheng Y-h, Liu T-l, Zhang C. Crocins: A comprehensive review of structural characteristics, pharmacokinetics and therapeutic effects. Fitoterapia 2021; 153: 1-16.
18. Hashemzaei M, Mamoulakis C, Tsarouhas K, Georgiadis G, Lazopoulos G, Tsatsakis A, et al. Crocin: A fighter against inflammation and pain. Food Chem Toxicol 2020; 143: 1-79.
19. Poursamimi J, Shariati-Sarabi Z, Tavakkol-Afshari J, Mohajeri SA, Mohammadi M. Crocus sativus (Saffron): An immunoregulatory factor in the autoimmune and non-autoimmune diseases. Iran J Allergy Asthma Immunol 2020; 19: 27-42.
20. Kermanshahi S, Ghanavati G, Abbasi-Mesrabadi M, Gholami M, Ulloa L, Motaghinejad M, et al. Novel neuroprotective potential of crocin in neurodegenerative disorders: An illustrated mechanistic review. Neurochem Res 2020; 45: 2573-2585.
21. Yousefi F, Arab FL, Rastin M, Tabasi NS, Nikkhah K, Mahmoudi M. Comparative assessment of immunomodulatory, proliferative, and anti-oxidant activities of crocin and crocetin on mesenchymal stem cells. J Cell Biochem 2021; 122:29-42.
22. Kalalinia F, Ghasim H, Farzad SA, Pishavar E, Ramezani M, Hashemi M. Comparison of the effect of crocin and crocetin, two major compounds extracted from saffron, on osteogenic differentiation of mesenchymal stem cells. Life Sci 2018; 208: 262-267.
23. Wang G, Zhou H, Gu Z, Gao Q, Shen G. Oct4 promotes cancer cell proliferation and migration and leads to poor prognosis associated with the survivin/STAT3 pathway in hepatocellular carcinoma. Oncol Rep 2018; 40: 979-987.
24. Ghourichaee SS, Powell EM, Leach JB. Enhancement of human neural stem cell self‐renewal in 3D hypoxic culture. Biotechnol Bioeng 2017; 114:1096-1106.
25. Strebinger D, Deluz C, Friman ET, Govindan S, Alber AB, Suter DM. Endogenous fluctuations of OCT 4 and SOX 2 bias pluripotent cell fate decisions. Mol Syst Biol 2019; 15: 1-19.
26. Zhang Z-Y, Hou Y-P, Zou X-Y, Xing X-Y, Ju G-Q, Zhong L, et al. Oct-4 enhanced the therapeutic effects of mesenchymal stem cell-derived extracellular vesicles in acute kidney injury. Kidney Blood Press Res 2020; 45: 95-108.
27. Bharti D, Shivakumar SB, Park J-K, Ullah I, Subbarao RB, Park J-S, et al. Comparative analysis of human Wharton’s jelly mesenchymal stem cells derived from different parts of the same umbilical cord. Cell Tissue Res 2018; 372:51-65.
28. Wu Q, Fang T, Lang H, Chen M, Shi P, Pang X, et al. Comparison of the proliferation, migration and angiogenic properties of human amniotic epithelial and mesenchymal stem cells and their effects on endothelial cells. Int J Mol Med 2017; 39: 918-926.
29. Rahimi HR, Mohammadpour AH, Dastani M, Jaafari MR, Abnous K, Mobarhan MG, et al. The effect of nano-curcumin on HbA1c, fasting blood glucose, and lipid profile in diabetic subjects: a randomized clinical trial. Avicenna J Phytomed 2016; 6: 567.
30. Mohajeri SA, Hosseinzadeh H, Keyhanfar F, Aghamohammadian J. Extraction of crocin from saffron (Crocus sativus) using molecularly imprinted polymer solid‐phase extraction. J Sep Sci 2010; 33:2302-2309.
31.Van Meerloo J, Kaspers GJ, Cloos J. Cell sensitivity assays: the MTT assay. Methods Mol Biol 2011; 731: 237-245.
32. 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: 107-114.
33. 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: 41-47.
34. Liu W-z, Ma Z-j, Li J-r, Kang X-w. Mesenchymal stem cell-derived exosomes: therapeutic opportunities and challenges for spinal cord injury. Stem Cell Res Ther 2021; 12: 1-15.
35. Li J, Zhang Q, Wang W, Lin F, Wang S, Zhao J. Mesenchymal stem cell therapy for ischemic stroke: a look into treatment mechanism and therapeutic potential. J Neurol 2021; 268:4095-4107.
36. Harrell CR, Volarevic V, Djonov V, Volarevic A. Therapeutic potential of exosomes derived from adipose tissue-sourced mesenchymal stem cells in the treatment of neural and retinal diseases. Int J Mol Sci 2022; 23: 1-14.
37. Udalamaththa VL, Jayasinghe CD, Udagama PV. Potential role of herbal remedies in stem cell therapy: proliferation and differentiation of human mesenchymal stromal cells. Stem Cell Res Ther 2016; 7: 1-8.
38.Kashyap D, Tuli HS, Yerer MB, Sharma A, Sak K, Srivastava S, et al., editors. Natural product-based nanoformulations for cancer therapy: Opportunities and challenges. Semin Cancer Biol 2021; 69: 5-23.
39. Joy R, George J, John F. Brief outlook on polymeric nanoparticles, micelles, niosomes, hydrogels and liposomes: Preparative methods and action. ChemistrySelect 2022; 7: 1-18 .
40. Qiu N, Du X, Ji J, Zhai G. A review of stimuli-responsive polymeric micelles for tumor-targeted delivery of curcumin. Drug Dev Ind Pharm 2021; 47: 839-856.
41. Kim SJ, Son TG, Park HR, Park M, Kim M-S, Kim HS, et al. Curcumin stimulates proliferation of embryonic neural progenitor cells and neurogenesis in the adult hippocampus. J Biol Chem 2008; 283: 14497-14505.
42. Son S, Kim K-T, Cho D-C, Kim H-J, Sung J-K, Bae J-S. Curcumin stimulates proliferation of spinal cord neural progenitor cells via a mitogen-activated protein kinase signaling pathway. J Korean Neurosurg Soc 2014; 56: 1-4.
43. Yousefi F, Arab FL, Jaafari MR, Rastin M, Tabasi N, Hatamipour M, et al. Immunoregulatory, proliferative and anti-oxidant effects of nanocurcuminoids on adipose-derived mesenchymal stem cells. EXCLI J 2019; 18: 405-421.
44. Pirmoradi S, Fathi E, Farahzadi R, Pilehvar-Soltanahmadi Y, Zarghami N. Curcumin affects adipose tissue-derived mesenchymal stem cell aging through TERT gene expression. Drug Res (Stuttg) 2018; 68: 213-221.
45. Wang X, Zhang Y, Yang Y, Zhang W, Luo L, Han F, et al. Curcumin pretreatment protects against hypoxia/reoxgenation injury via improvement of mitochondrial function, destabilization of HIF-1α and activation of Epac1-Akt pathway in rat bone marrow mesenchymal stem cells. Biomed Pharmacother 2019; 109: 1268-1275.
46. Li C, Luo T, Zheng Z, Murphy AR, Wang X, Kaplan DL. Curcumin-functionalized silk materials for enhancing adipogenic differentiation of bone marrow-derived human mesenchymal stem cells. Acta Biomater 2015; 11: 222-232.
47. Sabouni N, Marzouni HZ, Palizban S, Meidaninikjeh S, Kesharwani P, Jamialahmadi T, et al. Role of curcumin and its nanoformulations in the treatment of neurological diseases through the effects on stem cells. J Drug Target 2023; 31: 243-260.
48. Boozari M, Hosseinzadeh H. Crocin molecular signaling pathways at a glance: A comprehensive review. Phytother Res 2022; 36: 3859-3884.
49.Bakhtiary Z, Shahrooz R, Ahmadi A, Zarei L, editors. Evaluation of anti-oxidant effects of crocin on sperm quality in cyclophosphamide treated adult mice. Vet Res Forum 2014; 5: 213-218.
50. Noureini SK, Wink M. Antiproliferative effects of crocin in HepG2 cells by telomerase inhibition and hTERT down-regulation. Asian Pac J Cancer Prev 2012; 13: 2305-2309.
51. Hire RR, Srivastava S, Davis MB, Kumar Konreddy A, Panda D. Antiproliferative activity of crocin involves targeting of microtubules in breast cancer cells. Sci Rep 2017; 7: 1-11.
52. Mehri S, Abnous K, Khooei A, Mousavi SH, Shariaty VM, Hosseinzadeh H. Crocin reduced acrylamide-induced neurotoxicity in Wistar rat through inhibition of oxidative stress. Iran J Basic Med Sci 2015; 18: 902-908.
53. Matic I, Antunovic M, Brkic S, Josipovic P, Mihalic KC, Karlak I, et al. Expression of OCT-4 and SOX-2 in bone marrow-derived human mesenchymal stem cells during osteogenic differentiation. Open Access Maced J Med Sci 2016; 4: 9-16.
54. Tashakori M, Asadi F, Khorram F-S, Manshoori A, Hosseini-Chegeni A, Moghadam FM, et al. Effects of MRI on stemness properties of Wharton’s jelly-derived mesenchymal stem cells. Cell Tissue Bank 2022; 24: 523-533.
55. Han S-M, Han S-H, Coh Y-R, Jang G, Chan Ra J, Kang S-K, et al. Enhanced proliferation and differentiation of Oct4-and Sox2-overexpressing human adipose tissue mesenchymal stem cells. Exp Mol Med 2014; 46: 1-9.
56. Wang B, Hu Y, Liu L, Hu K, Tie R, He Y, et al. Phenotypical and functional characterization of bone marrow mesenchymal stem cells in patients with chronic graft-versus-host disease. Biol Blood Marrow Transplant 2015; 21: 1020-1028.
57. Yun JH, Park YG, Lee KM, Kim J, Nho CW. Curcumin induces apoptotic cell death via Oct4 inhibition and GSK‐3β activation in NCCIT cells. Mol Nutr Food Res 2015; 59: 1053-1062.
58. Mollaei H, Abedini MR, Hoshyar R. Suppressive effect of Crocin and cisplatin on pluripotency genes expression in human cervical cancer cells. Int J Cancer Manag 2017; 10: 1-3
59. Fan Y, Gu C, Zhang Y, Zhong B, Wang L, Zhou Z, et al. Oct4 and Sox2 overexpression improves the proliferation and differentiation of bone mesenchymal stem cells in Xiaomeishan porcine. Genet Mol Res 2013; 12: 6067-6079.
Iranian Journal of Basic Medical Sciences
Volume 27, Issue 9
September 2024
Pages 1187-1196

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