Preconditioning Can Improve Osteogenic Potential of Mesenchymal Stem Cells in Hypothyroidism


avatar Tayebeh Sanchooli 1 , *

Department of Anatomical Sciences, School of Medicine, Zahedan University of Medical Sciences, Zahedan, Iran

how to cite: Sanchooli T. Preconditioning Can Improve Osteogenic Potential of Mesenchymal Stem Cells in Hypothyroidism. Gene Cell Tissue.6(3):e95441. doi: 10.5812/gct.95441.

Dear Editor,

Thyroid hormones (TH) have a critical role in bone growth and metabolism (1) through direct or indirect action of TH on osteoblast and osteoclast cells (2). In patients with hypothyroidism, there is a reduction in bone turnover and increased fracture risk (3). Moreover, bone marrow mesenchymal stem cells (BMSC) have receptors for thyroid hormones (TRα, TRβ) and so they are T3-responsive cells (4). It has been shown that the osteogenic differentiation of MSCs is influenced by T3 in a dose-dependent manner. In this study, the 10 pM of T3 was the more effective dose on MSCs differentiation (5).

In addition, administration of TR-specific agonist GC-1 could improve the skeletal development in hypothyroid rats (1). Boeloni et al. reported a decrease in osteogenic potential of hypothyroid rat MSCs. The number of the mineralized nodules and expression of some estrogenic markers was reduced in hypothyroid MSCs (6).

Another study has demonstrated that thyroidectomy and the absence of hormonal induction could suppress in vitro osteogenic differentiation of mesenchymal stem cells. Alkaline phosphatase activity was low and expression of osteogenic markers, such as osteocalcin and osteopontin, was not detected in thyroidectomized rat’s MSCs (7).

It seems cell therapy for bone defects in hypothyroidism is difficult. Due to the limitation of osteogenic capacity of autogenic MSCs, another approach should be considered. On the other hand, normalizing hormonal levels using levothyroxine has problems, such as increased fracture risk within the first years of medication (3).

Normal allogeneic or xenogeneic stem cells can be used; however, an immunological reaction should be expected because of the different genetic content (8).

Preconditioning is a key strategy for improving MSCs properties in vitro and in vivo. The MSCs could be pretreated with various agents, such as trophic factors, cytokines, and physical factors before transplantation (9).

Laser has positive effects on MSCs. It has been reported that light emitting diodes (LED) increased proliferation and osteogenic differentiation of MSCs (10).

Some evidence has demonstrated that nanomaterials could enhance stem cell proliferation and differentiation (11). In vitro incubation with hydroxyapatite nanoparticles increases the expression of oseteogenic markers (ALP, osteocalcin, osteopontin, and Runx2) in hMSCs (12).

Application of MSCs conditioned media can improve osteogenic differentiation of MSCs. Conditioned media is cumulative of the wide range of growth factors and cytokines is secreted by MSCs. Many factors, such as insulin-like growth factor-1 (IGF-1), vascular endothelial growth factor (VEGF), hepatocyte growth factor (HGF), basic fibroblast growth factor (bFGF), interleukin 6 (IL-6), and bone morphogenetic proteins (BMPs) have been detected in the MSCs secretome (13). Some of these factors cooperate in bone regeneration (14).

Therefore, for cell therapy by autologous transplantation, preconditioning of hypothyroid stem cells with conditioned media, laser irradiation or nanomaterials before implantation may improve the osteogenic differentiation yield of stem cells and lead to further bone regeneration. Further studies and evaluation are required in vitro for a better understanding of the mechanism of this beneficial effect.

In conclusion, the lower osteogenic potential of the hypothyroid MSCs may improve with preconditioning by normal MSCs conditioned media or other factors before autologous transplantation.


  • 1.

    Freitas FR, Capelo LP, O'Shea PJ, Jorgetti V, Moriscot AS, Scanlan TS, et al. The thyroid hormone receptor beta-specific agonist GC-1 selectively affects the bone development of hypothyroid rats. J Bone Miner Res. 2005;20(2):294-304. doi: 10.1359/JBMR.041116. [PubMed: 15647824].

  • 2.

    Daei-Farshbaf N, Ardeshirylajimi A, Seyedjafari E, Piryaei A, Fadaei Fathabady F, Hedayati M, et al. Bioceramic-collagen scaffolds loaded with human adipose-tissue derived stem cells for bone tissue engineering. Mol Biol Rep. 2014;41(2):741-9. doi: 10.1007/s11033-013-2913-8. [PubMed: 24363224].

  • 3.

    Vestergaard P, Rejnmark L, Mosekilde L. Influence of hyper- and hypothyroidism, and the effects of treatment with antithyroid drugs and levothyroxine on fracture risk. Calcif Tissue Int. 2005;77(3):139-44. doi: 10.1007/s00223-005-0068-x. [PubMed: 16151671].

  • 4.

    Siddiqi A, Parsons MP, Lewis JL, Monson JP, Williams GR, Burrin JM. TR expression and function in human bone marrow stromal and osteoblast-like cells. J Clin Endocrinol Metab. 2002;87(2):906-14. doi: 10.1210/jcem.87.2.8226. [PubMed: 11836340].

  • 5.

    Boeloni JN, Ocarino NM, Melo AB, Silva JF, Castanheira P, Goes AM, et al. Dose-dependent effects of triiodothyronine on the osteogenic differentiation of rat bone marrow mesenchymal stem cells. Horm Res. 2009;72(2):88-97. doi: 10.1159/000232161. [PubMed: 19690426].

  • 6.

    Boeloni JN, de Ocarino MN, Silva JF, Correa CR, Bertollo CM, Hell RC, et al. Osteogenic differentiation of bone marrow mesenchymal stem cells of ovariectomized and non-ovariectomized female rats with thyroid dysfunction. Pathol Res Pract. 2013;209(1):44-51. doi: 10.1016/j.prp.2012.10.004. [PubMed: 23164717].

  • 7.

    Simsek T, Duruksu G, Okcu A, Aksoy A, Erman G, Utkan Z, et al. Effect of hypothyroidism in the thyroidectomized rats on immunophenotypic characteristics and differentiation capacity of adipose tissue derived stem cells. Eur Rev Med Pharmacol Sci. 2014;18(5):617-29. [PubMed: 24668701].

  • 8.

    Fekrazad R, Asefi S, Allahdadi M, Kalhori KA. Effect of photobiomodulation on mesenchymal stem cells. Photomed Laser Surg. 2016;34(11):533-42. doi: 10.1089/pho.2015.4029. [PubMed: 27070113].

  • 9.

    Hu C, Li L. Preconditioning influences mesenchymal stem cell properties in vitro and in vivo. J Cell Mol Med. 2018;22(3):1428-42. doi: 10.1111/jcmm.13492. [PubMed: 29392844]. [PubMed Central: PMC5824372].

  • 10.

    Peng F, Wu H, Zheng Y, Xu X, Yu J. The effect of noncoherent red light irradiation on proliferation and osteogenic differentiation of bone marrow mesenchymal stem cells. Lasers Med Sci. 2012;27(3):645-53. doi: 10.1007/s10103-011-1005-z. [PubMed: 22016038].

  • 11.

    Wei M, Li S, Le W. Nanomaterials modulate stem cell differentiation: Biological interaction and underlying mechanisms. J Nanobiotechnology. 2017;15(1):75. doi: 10.1186/s12951-017-0310-5. [PubMed: 29065876]. [PubMed Central: PMC5655945].

  • 12.

    Yang X, Li Y, Liu X, Zhang R, Feng Q. In vitro uptake of hydroxyapatite nanoparticles and their effect on osteogenic differentiation of human mesenchymal stem cells. Stem Cells Int. 2018;2018:2036176. doi: 10.1155/2018/2036176. [PubMed: 30018644]. [PubMed Central: PMC6029469].

  • 13.

    Kim HO, Choi SM, Kim HS. Mesenchymal stem cell-derived secretome and microvesicles as a cell-free therapeutics for neurodegenerative disorders. Tissue Eng Reg Med. 2013;10(3):93-101. doi: 10.1007/s13770-013-0010-7.

  • 14.

    Inukai T, Katagiri W, Yoshimi R, Osugi M, Kawai T, Hibi H, et al. Novel application of stem cell-derived factors for periodontal regeneration. Biochem Biophys Res Commun. 2013;430(2):763-8. doi: 10.1016/j.bbrc.2012.11.074. [PubMed: 23206704].

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