Original Article

The role of Spirulina platensis on the proliferation of rat bone marrow-derived mesenchymal stem cells


Background and Objectives: Spirulina platensis micro-algae have some effects on cellular procedures. The proliferative potential of mesenchymal stem cells (MSCs) will be decreased after repetitive passage.
Materials and Methods: The stromal cells were isolated, and then proven by differentiating to adipogenesis and osteoblastic lineage. The cell markers such as CD90 and CD105 were detected by flowcytometry. MSCs were treated with extract of S. platensis in logarithmic concentrations. MTT and ATP assays were done to determine cell proliferation capacity. The antioxidant and antimicrobial properties of the extract were evaluated.
Results: The results obtained from differentiation confirm cells’ potential for osteoblastic and adipoblastic differentiation. Detection of CD90 and CD105 markers over 70% proved that the majority of cells are MSCs. Statistical analyzes revealed a significant increase in MSCs proliferation in the concentration of 0.9 µl/ml S. platensis. DPPH assay demonstrated that the extract could scavenge free radicals up to 57%. Additionally, the extract showed the inhibition zone up to 11 mm against a different strain of bacteria by agar well diffusion assay.
Conclusion: Secreting nutritional elements, S. platensis extract can be used as an antioxidant, antimicrobial, and growth agent for enhancing the proliferation of MSCs. Furthermore, the optimum concentration for cell treatment with S. platensis’s extract was investigated.

1. Shabnama Kouser A, Arabi MS. Spirulina-an overview. Int J Pharm Pharm Sci 2012; 4: 9-15.
2. Campanella L, Russo M, Avino P. Free and total amino acid composition in blue-green algae. Ann. Chim 2002; 92: 343-352.
3. Colla L, Bertolin T, Costa J. Fatty acids profile of Spirulina platensis grown under different temperatures and nitrogen concentrations. Z Naturforsch C J Biosci 2004; 59: 55-59.
4. Golmakani M, Rezaei K, Mazidi S, Razavi S. γ‐Linolenic acid production by Arthrospira platensis using different carbon sources. Eur J Lipid Sci Technol 2012; 114: 306-314.
5. Jubie S, Ramesh P,Dhanabal P, Kalirajan R, Muruganantham N, Antony A. Synthesis, antidepressant and antimicrobial activities of some novel stearic acid analogues. Eur J Med Chem 2012; 54: 931-935.
6. Babadzhanov A, Abdusamatova N, Yusupova F, Faizullaeva N, Mezhlumyan L, Malikova M. Chemical composition of Spirulina platensis cultivated in Uzbekistan. Chem Nat Compd 2004; 40: 276-279.
7. Tokuşoglu Ö, Üunal M. Biomass nutrient profiles of three microalgae: Spirulina platensis, Chlorella vulgaris, and Isochrisis galbana. Curr Res Food Sci 2003; 68: 1144-1148.
8. Samadikuchaksaraei A, Gholipourmalekabadi M, Saberian M, Alitappeh M, Shahidi Delshad E. How does the supernatant of Lactobacillus acidophilus affect the proliferation and differentiation activities of rat bone marrow-derived stromal cells? Cell Mol Biol (Noisy-le-grand) 2016; 62: 1-6.
9. Halper J, Leshin L, Lewis S, Li W. Wound healing and angiogenic properties of supernatants from Lactobacillus cultures. Exp Biol Med (Maywood) 2003; 228: 1329-1337.
10. Li W, Brackett B, Halper J. Culture supernatant of Lactobacillus acidophilus stimulates proliferation of embryonic cells. Exp Biol Med (Maywood) 2005; 230: 494-500.
11. Baksh D, Song L, Tuan R. Adult mesenchymal stem cells: characterization, differentiation, and application in cell and gene therapy. J Cell Mol Med 2004; 8: 301-316.
12. Eslami-Arshaghi T, Salehi M, Soleimani M, Gholipourmalekabadi M, Mossahebi-Mohammadi M, Ardeshirylajimi A, Rajabi H. Lymphoid lineage differentiation potential of mouse nuclear transfer embryonic stem cells. Biologicals 2015; 43: 349-354.
13. Horwitz E, Gordon P, Koo W, Marx J, Neel M, McNall R, Hofmann T, et al. Isolated allogeneic bone marrow-derived mesenchymal cells engraft and stimulate growth in children with osteogenesis imperfecta: Implications for cell therapy of bone. Proc Natl Acad Sci U S A 2002; 99: 8932-8937.
14. Bianco P, Riminucci M, Gronthos S, Robey P. Bone marrow stromal stem cells: nature, biology, and potential applications. Stem Cells 2001; 19: 180-192.
15. Fuchs E, Segre J. Stem cells: a new lease on life. Cell 2000; 100: 143-155.
16. Fierro FA, Kalomoiris S, Sondergaard CS, Nolta JA. Effects on proliferation and differentiation of multipotent bone marrow stromal cells engineered to express growth factors for combined cell and gene therapy. Stem Cells 2011; 29: 1727-1737.
17. Chong, SG, Sato S, Kolb M, Gauldie J. Fibrocytes and fibroblasts—where are we now. Int J Biochem Cell Biol 2019; 116: 105595.
18. Jahani H, Kaviani S, Hassanpour-Ezatti M, Soleimani M, Kaviani Z, Zonoubi Z. The effect of aligned and random electrospun fibrous scaffolds on rat mesenchymal stem cell proliferation. Cell J 2012; 14: 31-38.
19. Minguell JJ, Erices A, Conget P. Mesenchymal stem cells. Exp Biol Med (Maywood) 2001; 226: 507-520.
20. Andrade MR, Costa JA. Outdoor and indoor cultivation of Spirulina platensis in the extreme south of Brazil. Z Naturforsch C J Biosci 2008; 63: 85-90.
21. Kato-Minoura T, Ogiwara Y, Yamano T, Fukuzawa H, Kamiya R. Chlamydomonas reinhardtii tubulin-gene disruptants for efficient isolation of strains bearing tubulin mutations. PloS One 2020; 15: e0242694.
22. Barbarino E, Lourenço SO. An evaluation of methods for extraction and quantification of protein from marine macro-and microalgae. J Appl Phycol 2005; 17: 447-460.
23. Zhang W-W, Duan X-J, Huang H, Zhang Y, Wang B-G. Evaluation of 28 marine algae from the Qingdao coast for antioxidative capacity and determination of antioxidant efficiency and total phenolic content of fractions and subfractions derived from Symphyocladia latiuscula (Rhodomelaceae). J Appl Phycol 2007; 19: 97-108.
24. Kaushik P, Chauhan A. In vitro antibacterial activity of laboratory grown culture of Spirulina platensis. Indian J Microbiol 2008; 48: 348-352.
25. 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: 7513404.
26. Sun S, Guo Z, Xiao X, Liu B, Liu X, Tang P-H, Mao N. Isolation of mouse marrow mesenchymal progenitors by a novel and reliable method. Stem cells 2003; 21: 527-535.
27. Nadri S, Soleimani M, Hosseni RH, Massumi M, Atashi A, Izadpanah R. An efficient method for isolation of murine bone marrow mesenchymal stem cells. Int J Dev Biol 2007; 51: 723-729.
28. Dominici M, Le Blanc K, Mueller I, Slaper-Cortenbach I, Marini F, Krause D, et al. Minimal criteria for defining multipotent mesenchymal stromal cells. The International Society for Cellular Therapy position statement. Cytotherapy 2006; 8: 315-317.
29. Bortolotti F, Ukovich L, Razban V, Martinelli V, Ruozi G, Pelos B, et al. In vivo therapeutic potential of mesenchymal stromal cells depends on the source and the isolation procedure. Stem cell reports 2015; 4: 332-339.
30. Sekiya I, Larson BL, Vuoristo JT, Cui J-G, Prockop DT. Adipogenic differentiation of human adult stem cells from bone marrow stroma (MSCs). J Bone Miner Res 2004; 19: 256-264.
31. Li J, Curley JL, Floyd ZE, Wu X, Halvorsen YD, Gimble JM. Isolation of human adipose-derived stem cells from Lipoaspirates. Methods Mol Biol 2018; 1773: 155-165.
32. Kern S, Eichler H, Stoeve J, Klüter H, Bieback K. Comparative analysis of mesenchymal stem cells from bone marrow, umbilical cord blood, or adipose tissue. Stem cells 2006; 24: 1294-1301.
33. Aslantürk ÖS. In Vitro Cytotoxicity and Cell Viability Assays: Principles, Advantages, and Disadvantages. Genotoxicity-A Predictable Risk to Our Actual World. 2018.
34. Fuchs C, Schenk MS, Pham L, Cui L, Anderson RR, Tam J. Photobiomodulation response from 660 nm is different and more durable than that from 980 nm. Lasers Surg Med 2021; 53: 1279-1293.
35. Chu W, Lim YW, Radhakrishnan AK, Lim PC. Protective effect of aqueous extract from Spirulina platensis against cell death induced by free radicals. J Ethnopharmacol 2010; 10: 1-8.
36. Choi Y, Jang J, Koo HJ, Tanaka M, Lee KH, Choi J. Alginate-chitosan Hydrogel patch with beta-glucan nanoemulsion for antibacterial applications. Biotechnol Bioprocess Eng 2021; 26: 71-77.
37. Ozdemir G, Karabay NU, Dalay MC, Pazarbasi B. Antibacterial activity of volatile component and various extracts of Spirulina platensis. Phytother Res 2004; 18: 754-757.
38. Baksh D, Yao R, Tuan RS. Comparison of proliferative and multilineage differentiation potential of human mesenchymal stem cells derived from umbilical cord and bone marrow. Stem cells 2007; 25: 1384-1392.
39. Saberian M, Seyedjafari E, Zargar SJ, Mahdavi FS, Sanaei‐rad P. Fabrication and characterization of alginate/chitosan hydrogel combined with honey and aloe vera for wound dressing applications. J Appl Polym Sci 2021; 138: 864-873.
40. Gad AS, Khadrawy YA, El-Nekeety AA, Mohamed SR, Hassan NS, Abdel-Wahhab MA. Antioxidant activity and hepatoprotective effects of whey protein and Spirulina in rats. Nutrition 2011; 27: 582-589.
41. Zhang J. Peng JP. Enhanced proliferation and differentiation of mesenchymal stem cells by astaxanthin-encapsulated polymeric micelles. PLoS One 2019; 14(5):e0216755.
42. Kaushik P, Chauhan M. In vitro antibacterial activity of laboratory grown culture of Spirulina platensis. Indian J Microbiol 2008; 48: 348-352.
43. Rao AR, Reddy AH, Aradhya S. Antibacterial properties of Spirulina platensis, Haematococcus pluvialis, Botryococcus braunii micro algal extracts. Curr Trends Biotechnol Pharm 2010; 43: 809-819.
44. Park NH, Choi JS, Hwang SY, Kim YC, Hong YK, Cho KK, Choi IS. Antimicrobial activities of stearidonic and gamma-linolenic acids from the green seaweed Enteromorpha linza against several oral pathogenic bacteria. Bot Stud 2013; 54: 39.
45. Mishra PM, Sree A. Chemical investigation of Finlaysonia obovata: part I–a rare triterpene acid showing antibacterial activity against fish pathogens. Nat Prod Res 2008; 22: 801-807.
46. Lee YS, Kang MH, Cho SY, Jeong CS. Effects of constituents of Amomum xanthioides on gastritis in rats and on growth of gastric cancer cells. Arch Pharm Res 2007; 30: 436-443.
47. Abdel-Moneim A, Saadony ME, Shehata AM, Saad AM, Aldhumri SA, Ouda SM, Mesalam BS. Antioxidant and antimicrobial activities of Spirulina platensis extracts and biogenic selenium nanoparticles against selected pathogenic bacteria and fungi. Saudi J Biol Sci 2022; 29: 1197-1209.
48. Amerikova M, Pencheva El-Tibi I, Maslarska V, Bozhanov S, Tachkov KJ. Antimicrobial activity, mechanism of action, and methods for stabilisation of defensins as new therapeutic agents. Biotechnol Biotechnol Equip 2019; 33: 671-682.
49. Mundt S, Kreitlow S, Jansen R. Fatty acids with antibacterial activity from the cyanobacterium Oscillatoria redekei HUB 051. E J Appl Psychol 2003; 15: 263-267.
50. Alshuniaber MA, Krishnamoorthy R, AlQhtani BS. Antimicrobial activity of polyphenolic compounds from Spirulina against food-borne bacterial pathogens. Saudi J Biol Sci 2021; 28: 459-464.
51. Ambati D, Reddy AH, Aradhya S. Antibacterial properties of Spirulina platensis, Haematococcus pluvialis, Botryococcus braunii micro algal extracts. Curr Trends Biotechnol Pharm 2010; 4: 809-819.
52. Rojas M, Xu J, Woods CR, Mora AL, Spears W, Roman J, Brigham KL. Bone marrow–derived mesenchymal stem cells in repair of the injured lung. Am J Respir Cell Mol Biol 2005; 33: 145-152.
53. Letsiou S, Bakea A, Goff GL, Lopes L, Gardikis K, Weis M, Ouazzani M. Marine fungus Aspergillus chevalieri TM2-S6 extract protects skin fibroblasts from oxidative stress. Marine Drugs 2020; 18: 460.
54. Taylor SE, Clegg P. Collection and propagation methods for mesenchymal stromal cells. Vet Clin North Am Equine Pract 2011; 27: 263-274.
55. Khan Z, Bhadouria P, Bisen CP. Nutritional and therapeutic potential of Spirulina. Curr Pharm Biotechnol 2005; 6:373-379.
56. Morist A, Montesinos J, Cusido J, Godia B. Recovery and treatment of Spirulina platensis cells cultured in a continuous photobioreactor to be used as food. Process Biochem 2001; 37: 535-547.
57. Bachstetter AD, Jernberg J, Schlunk A, Vila JL, Hudson C, Cole MJ, Sanberg C. Spirulina promotes stem cell genesis and protects against LPS induced declines in neural stem cell proliferation. PLoS One 2010; 5(5): e10496.
58. Nawrocka D, Kornicka k, Śmieszek A, Marycz K. Spirulina platensis improves mitochondrial function impaired by elevated oxidative stress in adipose-derived mesenchymal stromal cells (ASCs) and intestinal epithelial cells (IECs), and enhances insulin sensitivity in equine metabolic syndrome (EMS) horses. Mar Drugs 2017; 15: 237.
IssueVol 15 No 1 (2023) QRcode
SectionOriginal Article(s)
DOI https://doi.org/10.18502/ijm.v15i1.11925
Spirulina platensis; Mesenchymal stem cells; Cell proliferation; Antioxidant; Antibacterial agents

Rights and permissions
Creative Commons License This work is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License.
How to Cite
Saberian M, Shahidi Delshad E. The role of Spirulina platensis on the proliferation of rat bone marrow-derived mesenchymal stem cells. Iran J Microbiol. 2023;15(1):111-120.