GGM

Journal of Gerontology

and Geriatric MedicineISSNISSN 2697-4509 (Online)

GGM

Journal of Gerontology

and Geriatric MedicineISSN 2697-4509 (Online)

Article

ปีที่ 24 ฉบับที่ 1 มกราคม-มิถุนายน 2568 (1-10)

The Enhancing Effect of Dihydromorin, a Flavanonol Compound Isolated from Maclura Cochinchinensis (Kae-Lae), on the Proliferation and Differentiation of Umbilical Cord-Derived Mesenchymal Stem Cells into Osteoblasts.

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Kittinan Shangchai¹, Duangrat Tantikanlayaporn², Nareerat Sutjarit³

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¹Master of Science Program in Nutrition, Faculty of Medicine Ramathibodi Hospital and Institute of Nutrition, Mahidol University.
²Stem Cell and Molecular Biology, Faculty of Medicine, Thammasat University, Pathum Thani.
³Graduate Program in Nutrition, Faculty of Medicine Ramathibodi Hospital and Institute of Nutrition, Mahidol University.

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Abstract

Mesenchymal stem cells isolated from umbilical cord tissue (UC-MSCs) are attractive candidates for cell-based therapy and regenerative medicine due to their remarkable self-renewal and differentiation ability. However, UC-MSCs obtained is limited. Therefore, searching for safe and effective agents in promoting the proliferation and differentiation of UC-MSCs is an alternative strategy to improve the efficacy of MSC-based therapy in degenerative disorders. Phytochemicals isolated from medicinal plants, such as polyphenols, flavonoids, and other plant-derived chemicals have been reported to exhibit proliferative and anti-senescent effects in MSCs. This study aims to evaluate the effects of dihydromorin, a flavanonol compound from Maclura Cochinensis or Thai herbs as "Kae-Lae", a medicinal plant found in Thailand on the proliferation and osteogenic differentiation of UC-MSCs. Firstly, MSCs were isolated from leftover umbilical cord tissue and characterized for their morphology, immunophenotype, and multi-lineage potentials. UC-MSCs were treated with different concentrations of dihydromorin. The results demonstrated that dihydromorin at 1-10 µM increased the proliferation of UC-MSCs as determined by the MTT assay and the growth curve analysis. Interestingly, dihydromorin accelerated the osteogenic differentiation of UC-MSCs as indicated by the increased alkaline phosphatase (ALP) and calcium deposition as determined by ALP staining and Alizarin Red S staining, respectively. Dihydromorin also enhanced osteogenic markers genes, including RUNX2, OSX, ALP, OCN, and COL1A1. The osteogenic effect of dihydromorin tended to be mediated through the activation of the Wnt/β-catenin signaling pathway as active-β-catenin is increased by dihydromorin which can be translocated into the nucleus and activate the expression of genes involved in cell proliferation and osteogenic differentiation of UC-MSCs. This study demonstrates the osteogenic potential of dihydromorin in human UC-MSCs, providing a foundation for future investigations into its possible applications in bone regeneration and therapeutic strategies.

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Keyword

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Kae-Lae, dihydromorin, umbilical cord-derived mesenchymal stem cells, proliferation, osteogenic differentiation, cell therapy, and regenerative medicine

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References

  1. Park JS, Suryaprakash S, Lao Y-H, Leong KW. Engineering mesenchymal stem cells for regenerative medicine and drug delivery. Methods. 2015;84:3-16.
  2. Marion NW, Mao JJ. Mesenchymal stem cells and tissue engineering. Methods Enzymol. 2006;420:339-61.
  3. Tian C, Ye L, Zhao X, Zhu X, Xu J, Pan X. Umbilical cord mesenchymal stem cells: A novel approach to intervention of ovarian ageing. Regenerative Therapy. 2024;26:590-8.
  4. Kerstan A, Niebergall-Roth E, Esterlechner J, Schröder HM, Gasser M, Waaga-Gasser AM, et al. Ex vivo-expanded highly pure ABCB5+ mesenchymal stromal cells as Good Manufacturing Practice-compliant autologous advanced therapy medicinal product for clinical use: process validation and first in-human data. Cytotherapy. 2021;23(2):165-75.
  5. Liu Y, Chen Q. Senescent Mesenchymal Stem Cells: Disease Mechanism and Treatment Strategy. Curr Mol Biol Rep. 2020;6(4):173-82.
  6. Mastrolia I, Foppiani EM, Murgia A, Candini O, Samarelli AV, Grisendi G, et al. Challenges in Clinical Development of Mesenchymal Stromal/Stem Cells: Concise Review. Stem Cells Transl Med. 2019;8(11):1135-48.
  7. 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.
  8. Rueankham L, Panyajai P, Saiai A, Rungrojsakul M, Tima S, Chiampanichayakul S, et al. Biological activities of extracts and compounds from Thai Kae-Lae (Maclura cochinchinensis (Lour.) Corner). BMC Complementary Medicine and Therapies. 2023;23(1):191.
  9. Zahoor H, Watchaputi K, Hata J, Pabuprapap W, Suksamrarn A, Chua LS, et al. Model yeast as a versatile tool to examine the antioxidant and anti-ageing potential of flavonoids, extracted from medicinal plants. Frontiers in pharmacology [Internet]. 2022 2022; 13:[980066 p.].
  10. Wan J, Ma T, Jin Y, Qiu S. The effects of morin on bone regeneration to accelerate healing in bone defects in mice. Int J Immunopathol Pharmacol. 2020;34:2058738420962909.
  11. Ansari S, Ito K, Hofmann S. Alkaline Phosphatase Activity of Serum Affects Osteogenic Differentiation Cultures. ACS Omega. 2022;7(15):12724-33.
  12. Zhou P, Shi J-M, Song J-E, Han Y, Li H-J, Song Y-M, et al. Establishing a deeper understanding of the osteogenic differentiation of monolayer cultured human pluripotent stem cells using novel and detailed analyses. Stem Cell Research & Therapy. 2021;12(1):41.
  13. Zhang R, Kang KA, Piao MJ, Maeng YH, Lee KH, Chang WY, et al. Cellular protection of morin against the oxidative stress induced by hydrogen peroxide. Chem Biol Interact. 2009;177(1):21-7.
  14. Davis KE, Joseph SJ, Janssen PH. Effects of growth medium, inoculum size, and incubation time on culturability and isolation of soil bacteria. Appl Environ Microbiol. 2005;71(2):826-34.
  15. Chen D, Liu S, Chu X, Reiter J, Gao H, McGuire P, et al. Osteogenic Differentiation Potential of Mesenchymal Stem Cells Using Single Cell Multiomic Analysis. Genes (Basel). 2023;14(10).
  16. Föger-Samwald U, Dovjak P, Azizi-Semrad U, Kerschan-Schindl K, Pietschmann P. Osteoporosis: Pathophysiology and therapeutic options. Excli j. 2020;19:1017-37.
  17. Hanna H, Mir LM, Andre FM. In vitro osteoblastic differentiation of mesenchymal stem cells generates cell layers with distinct properties. Stem Cell Res Ther. 2018;9(1):203.
  18. Xu J, Li Z, Hou Y, Fang W. Potential mechanisms underlying the Runx2 induced osteogenesis of bone marrow mesenchymal stem cells. Am J Transl Res. 2015;7(12):2527-35.
  19. Sinha KM, Zhou X. Genetic and molecular control of osterix in skeletal formation. J Cell Biochem. 2013;114(5):975-84.
  20. Chen Y, Yang S, Lovisa S, Ambrose CG, McAndrews KM, Sugimoto H, et al. Type-I collagen produced by distinct fibroblast lineages reveals specific function during embryogenesis and Osteogenesis Imperfecta. Nat Commun. 2021;12(1):7199.
  21. Zoch ML, Clemens TL, Riddle RC. New insights into the biology of osteocalcin. Bone. 2016;82:42-9.
  22. Yu M, Qin K, Fan J, Zhao G, Zhao P, Zeng W, et al. The evolving roles of Wnt signaling in stem cell proliferation and differentiation, the development of human diseases, and therapeutic opportunities. Genes Dis. 2024;11(3):101026.
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