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Activation of Wnt3a signaling promotes myogenic differentiation of mesenchymal stem cells in mdx mice.
Acta Pharmacol Sin. 2016 Jul; 37(7):873-81.AP

Abstract

AIM

Duchenne muscular dystrophy (DMD) is an X-linked genetic muscular disorder with no effective treatment at present. Mesenchymal stem cell (MSC) transplantation has been used to treat DMD, but the efficiency is low. Our previous studies show that activation of Wnt3a signaling promotes myogenic differentiation of MSCs in vitro. Here we report an effective MSC transplantation therapy in mdx mice by activation of Wnt3a signaling.

METHODS

MSCs were isolated from mouse bone marrow, and pretreated with Wnt3a-conditioned medium (Wnt3a-CM), then transplanted into mdx mice. The recipient mice were euthanized at 4, 8, 12, 16 weeks after the transplantation, and muscle pathological changes were examined. The expression of dystrophin in muscle was detected using immunofluorescence staining, RT-PCR and Western blotting.

RESULTS

Sixteen weeks later, transplantation of Wnt3a-pretreated MSCs in mdx mice improved the characteristics of dystrophic muscles evidenced by significant reductions in centrally nucleated myofibers, the variability range of cross-sectional area (CSA) and the connective tissue area of myofibers. Furthermore, transplantation of Wnt3a-pretreated MSCs in mdx mice gradually and markedly increased the expression of dystrophin in muscle, and improved the efficiency of myogenic differentiation.

CONCLUSION

Transplantation of Wnt3a-pretreated MSCs in mdx mice results in long-term amelioration of the dystrophic phenotype and restores dystrophin expression in muscle. The results suggest that Wnt3a may be a promising candidate for the treatment of DMD.

Authors+Show Affiliations

Department of Geriatric Neurology, Chinese People's Liberation Army General Hospital, Beijing 100853, China.Department of Neurology, Beijing Friendship Hospital, Capital Medical University, Beijing 100050, China.Department of Neurology, First Affiliated Hospital, Sun Yat-sen University, Guangzhou 510080, China.Department of Neurology, First Affiliated Hospital, Sun Yat-sen University, Guangzhou 510080, China.Department of Neurology, First Affiliated Hospital, Sun Yat-sen University, Guangzhou 510080, China.Department of Neurology, First Affiliated Hospital, Sun Yat-sen University, Guangzhou 510080, China.Department of Neurology, First Affiliated Hospital, Sun Yat-sen University, Guangzhou 510080, China.

Pub Type(s)

Journal Article

Language

eng

PubMed ID

27133298

Citation

Shang, Yan-Chang, et al. "Activation of Wnt3a Signaling Promotes Myogenic Differentiation of Mesenchymal Stem Cells in Mdx Mice." Acta Pharmacologica Sinica, vol. 37, no. 7, 2016, pp. 873-81.
Shang YC, Wang SH, Xiong F, et al. Activation of Wnt3a signaling promotes myogenic differentiation of mesenchymal stem cells in mdx mice. Acta Pharmacol Sin. 2016;37(7):873-81.
Shang, Y. C., Wang, S. H., Xiong, F., Peng, F. N., Liu, Z. S., Geng, J., & Zhang, C. (2016). Activation of Wnt3a signaling promotes myogenic differentiation of mesenchymal stem cells in mdx mice. Acta Pharmacologica Sinica, 37(7), 873-81. https://doi.org/10.1038/aps.2016.38
Shang YC, et al. Activation of Wnt3a Signaling Promotes Myogenic Differentiation of Mesenchymal Stem Cells in Mdx Mice. Acta Pharmacol Sin. 2016;37(7):873-81. PubMed PMID: 27133298.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Activation of Wnt3a signaling promotes myogenic differentiation of mesenchymal stem cells in mdx mice. AU - Shang,Yan-Chang, AU - Wang,Shu-Hui, AU - Xiong,Fu, AU - Peng,Fu-Ning, AU - Liu,Zhen-Shan, AU - Geng,Jia, AU - Zhang,Cheng, Y1 - 2016/05/02/ PY - 2015/09/15/received PY - 2016/01/04/accepted PY - 2016/5/3/entrez PY - 2016/5/3/pubmed PY - 2017/8/3/medline SP - 873 EP - 81 JF - Acta pharmacologica Sinica JO - Acta Pharmacol Sin VL - 37 IS - 7 N2 - AIM: Duchenne muscular dystrophy (DMD) is an X-linked genetic muscular disorder with no effective treatment at present. Mesenchymal stem cell (MSC) transplantation has been used to treat DMD, but the efficiency is low. Our previous studies show that activation of Wnt3a signaling promotes myogenic differentiation of MSCs in vitro. Here we report an effective MSC transplantation therapy in mdx mice by activation of Wnt3a signaling. METHODS: MSCs were isolated from mouse bone marrow, and pretreated with Wnt3a-conditioned medium (Wnt3a-CM), then transplanted into mdx mice. The recipient mice were euthanized at 4, 8, 12, 16 weeks after the transplantation, and muscle pathological changes were examined. The expression of dystrophin in muscle was detected using immunofluorescence staining, RT-PCR and Western blotting. RESULTS: Sixteen weeks later, transplantation of Wnt3a-pretreated MSCs in mdx mice improved the characteristics of dystrophic muscles evidenced by significant reductions in centrally nucleated myofibers, the variability range of cross-sectional area (CSA) and the connective tissue area of myofibers. Furthermore, transplantation of Wnt3a-pretreated MSCs in mdx mice gradually and markedly increased the expression of dystrophin in muscle, and improved the efficiency of myogenic differentiation. CONCLUSION: Transplantation of Wnt3a-pretreated MSCs in mdx mice results in long-term amelioration of the dystrophic phenotype and restores dystrophin expression in muscle. The results suggest that Wnt3a may be a promising candidate for the treatment of DMD. SN - 1745-7254 UR - https://www.unboundmedicine.com/medline/citation/27133298/Activation_of_Wnt3a_signaling_promotes_myogenic_differentiation_of_mesenchymal_stem_cells_in_mdx_mice_ L2 - https://doi.org/10.1038/aps.2016.38 DB - PRIME DP - Unbound Medicine ER -