Myogenic differentiation potential of human tonsil-derived mesenchymal stem cells and their potential for use to promote skeletal muscle regeneration

Park,Saeyoung; Choi,Yoonyoung; Jung,Namhee; Yu,Yeonsil; Ryu,Kyung-Ha; Kim,Han  Su; Jo,Inho; Choi,Byung-Ok; Jung,Sung-Chul

doi:10.3892/ijmm.2016.2536

Myogenic differentiation potential of human tonsil-derived mesenchymal stem cells and their potential for use to promote skeletal muscle regeneration

Authors:
- Saeyoung Park
- Yoonyoung Choi
- Namhee Jung
- Yeonsil Yu
- Kyung-Ha Ryu
- Han Su Kim
- Inho Jo
- Byung-Ok Choi
- Sung-Chul Jung
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Affiliations: Department of Biochemistry, School of Medicine, Ewha Womans University, Seoul 07985, Republic of Korea, Department of Molecular Medicine, School of Medicine, Ewha Womans University, Seoul 07985, Republic of Korea, Department of Pediatrics, School of Medicine, Ewha Womans University, Seoul 07985, Republic of Korea, Department of Otorhinolaryngology - Head and Neck Surgery, School of Medicine, Ewha Womans University, Seoul 07985, Republic of Korea, Department of Neurology, Samsung Medical Center, Sungkyunkwan University, Seoul 06351, Republic of Korea
Published online on: March 22, 2016 https://doi.org/10.3892/ijmm.2016.2536
Pages: 1209-1220
Copyright: © Park et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

Stem cells are regarded as an important source of cells which may be used to promote the regeneration of skeletal muscle (SKM) which has been damaged due to defects in the organization of muscle tissue caused by congenital diseases, trauma or tumor removal. In particular, mesenchymal stem cells (MSCs), which require less invasive harvesting techniques, represent a valuable source of cells for stem cell therapy. In the present study, we demonstrated that human tonsil-derived MSCs (T-MSCs) may differentiate into myogenic cells in vitro and that the transplantation of myoblasts and myocytes generated from human T-MSCs mediates the recovery of muscle function in vivo. In order to induce myogenic differentiation, the T-MSC-derived spheres were cultured in Dulbecco's modified Eagle's medium/nutrient mixture F-12 (DMEM/F‑12) supplemented with 1 ng/ml transforming growth factor-β, non-essential amino acids and insulin‑transferrin-selenium for 4 days followed by culture in myogenic induction medium [low-glucose DMEM containing 2% fetal bovine serum (FBS) and 10 ng/ml insulin‑like growth factor 1 (IGF1)] for 14 days. The T-MSCs sequentially differentiated into myoblasts and skeletal myocytes, as evidenced by the increased expression of skeletal myogenesis-related markers [including α-actinin, troponin I type 1 (TNNI1) and myogenin] and the formation of myotubes in vitro. The in situ transplantation of T-MSCs into mice with a partial myectomy of the right gastrocnemius muscle enhanced muscle function, as demonstrated by gait assessment (footprint analysis), and restored the shape of SKM without forming teratomas. Thus, T-MSCs may differentiate into myogenic cells and effectively regenerate SKM following injury. These results demonstrate the therapeutic potential of T-MSCs to promote SKM regeneration following injury.

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1	Chen W, Xie M, Yang B, Bharadwaj S, Song L, Liu G, Yi S, Ye G, Atala A and Zhang Y: Skeletal myogenic differentiation of human urine-derived cells as a potential source for skeletal muscle regeneration. J Tissue Eng Regen Med. Jun 19–2014.Epub ahead of print. View Article : Google Scholar : PubMed/NCBI
2	Desai VD, Hsia HC and Schwarzbauer JE: Reversible modulation of myofibroblast differentiation in adipose-derived mesenchymal stem cells. PLoS One. 9:e868652014. View Article : Google Scholar : PubMed/NCBI
3	Gunetti M, Tomasi S, Giammò A, Boido M, Rustichelli D, Mareschi K, Errichiello E, Parola M, Ferrero I, Fagioli F, et al: Myogenic potential of whole bone marrow mesenchymal stem cells in vitro and in vivo for usage in urinary incontinence. PLoS One. 7:e455382012. View Article : Google Scholar : PubMed/NCBI
4	Hosoyama T, McGivern JV, Van Dyke JM, Ebert AD and Suzuki M: Derivation of myogenic progenitors directly from human pluripotent stem cells using a sphere-based culture. Stem Cells Transl Med. 3:564–574. 2014. View Article : Google Scholar : PubMed/NCBI
5	Pereira T, Gärtner A, Amorim I, Armada-da-Silva P, Gomes R, Pereira C, França ML, Morais DM, Rodrigues MA, Lopes MA, et al: Biomaterials and stem cell therapies for injuries associated to skeletal muscular tissues. Advances in Biomaterials Science and Biomedical Applications. Pignatello R: InTech; Rijeka: pp. 329–355. 2013
6	Kang JS and Krauss RS: Muscle stem cells in developmental and regenerative myogenesis. Curr Opin Clin Nutr Metab Care. 13:243–248. 2010. View Article : Google Scholar : PubMed/NCBI
7	Motohashi N, Asakura Y and Asakura A: Isolation, culture, and transplantation of muscle satellite cells. J Vis Exp. 86:e508462014.
8	Shi X and Garry DJ: Muscle stem cells in development, regeneration, and disease. Genes Dev. 20:1692–1708. 2006. View Article : Google Scholar : PubMed/NCBI
9	Darabi R, Gehlbach K, Bachoo RM, Kamath S, Osawa M, Kamm KE, Kyba M and Perlingeiro RC: Functional skeletal muscle regeneration from differentiating embryonic stem cells. Nat Med. 14:134–143. 2008. View Article : Google Scholar : PubMed/NCBI
10	Mizuno Y, Chang H, Umeda K, Niwa A, Iwasa T, Awaya T, Fukada S, Yamamoto H, Yamanaka S, Nakahata T and Heike T: Generation of skeletal muscle stem/progenitor cells from murine induced pluripotent stem cells. FASEB J. 24:2245–2253. 2010. View Article : Google Scholar : PubMed/NCBI
11	Dezawa M, Ishikawa H, Itokazu Y, Yoshihara T, Hoshino M, Takeda S, Ide C and Nabeshima Y: Bone marrow stromal cells generate muscle cells and repair muscle degeneration. Science. 309:314–317. 2005. View Article : Google Scholar : PubMed/NCBI
12	Di Rocco G, Iachininoto MG, Tritarelli A, Straino S, Zacheo A, Germani A, Crea F and Capogrossi MC: Myogenic potential of adipose-tissue-derived cells. J Cell Sci. 119:2945–2952. 2006. View Article : Google Scholar : PubMed/NCBI
13	Nunes VA, Cavaçana N, Canovas M, Strauss BE and Zatz M: Stem cells from umbilical cord blood differentiate into myotubes and express dystrophin in vitro only after exposure to in vivo muscle environment. Biol Cell. 99:185–196. 2007. View Article : Google Scholar
14	Kim JA, Shon YH, Lim JO, Yoo JJ, Shin HI and Park EK: MYOD mediates skeletal myogenic differentiation of human amniotic fluid stem cells and regeneration of muscle injury. Stem Cell Res Ther. 4:1472013. View Article : Google Scholar : PubMed/NCBI
15	Park S, Kim E, Koh SE, Maeng S, Lee WD, Lim J, Shim I and Lee YJ: Dopaminergic differentiation of neural progenitors derived from placental mesenchymal stem cells in the brains of Parkinson's disease model rats and alleviation of asymmetric rotational behavior. Brain Res. 1466:158–166. 2012. View Article : Google Scholar : PubMed/NCBI
16	Kerkis I, Kerkis A, Dozortsev D, Stukart-Parsons GC, Gomes Massironi SM, Pereira LV, Caplan AI and Cerruti HF: Isolation and characterization of a population of immature dental pulp stem cells expressing OCT-4 and other embryonic stem cell markers. Cells Tissues Organs. 184:105–116. 2006. View Article : Google Scholar
17	Ryu KH, Cho KA, Park HS, Kim JY, Woo SY, Jo I, Choi YH, Park YM, Jung SC, Chung SM, et al: Tonsil-derived mesenchymal stromal cells: evaluation of biologic, immunologic and genetic factors for successful banking. Cytotherapy. 14:1193–1202. 2012. View Article : Google Scholar : PubMed/NCBI
18	Ting CH, Ho PJ and Yen BL: Age-related decreases of serum-response factor levels in human mesenchymal stem cells are involved in skeletal muscle differentiation and engraftment capacity. Stem Cells Dev. 23:1206–1216. 2014. View Article : Google Scholar : PubMed/NCBI
19	Djouad F, Jackson WM, Bobick BE, Janjanin S, Song Y, Huang GT and Tuan RS: Activin A expression regulates multipotency of mesenchymal progenitor cells. Stem Cell Res Ther. 1:112010. View Article : Google Scholar : PubMed/NCBI
20	Park M, Kim YH, Woo SY, Lee HJ, Yu Y, Kim HS, Park YS, Jo I, Park JW, Jung SC, et al: Tonsil-derived mesenchymal stem cells ameliorate CCI4-induced liver fibrosis in mice via autophagy activation. Sci Rep. 5:86162015. View Article : Google Scholar
21	Yu Y, Park YS, Kim HS, Kim HY, Jin YM, Jung SC, Ryu KH and Jo I: Characterization of long-term in vitro culture-related alterations of human tonsil-derived mesenchymal stem cells: role for CCN1 in replicative senescence-associated increase in osteogenic differentiation. J Anat. 225:510–518. 2014. View Article : Google Scholar : PubMed/NCBI
22	Park M, Kim YH, Ryu JH, Woo SY and Ryu KH: Immune suppressive effects of tonsil-derived mesenchymal stem cells on mouse bone-marrow-derived dendritic cells. Stem Cells Int. 2015:1065402015. View Article : Google Scholar : PubMed/NCBI
23	Ryu KH, Kim SY, Kim YR, Woo SY, Sung SH, Kim HS, Jung SC, Jo I and Park JW: Tonsil-derived mesenchymal stem cells alleviate concanavalin A-induced acute liver injury. Exp Cell Res. 326:143–154. 2014. View Article : Google Scholar : PubMed/NCBI
24	Park YS, Hwang S, Jin YM, Yu Y, Jung SA, Jung SC, Ryu KH, Kim HS and Jo I: CCN1 secreted by tonsil-derived mesenchymal stem cells promotes endothelial cell angiogenesis via integrin α_vβ₃ and AMPK. J Cell Physiol. 230:140–149. 2015. View Article : Google Scholar
25	Mauro A: Satellite cell of skeletal muscle fibers. J Biophys Biochem Cytol. 9:493–495. 1961. View Article : Google Scholar : PubMed/NCBI
26	Chargé SBP and Rudnicki MA: Cellular and molecular regulation of muscle regeneration. Physiol Rev. 84:209–238. 2004. View Article : Google Scholar : PubMed/NCBI
27	Guide for the Care and Use of Laboratory Animals. 8th edition. National Research Council. The National Academies Press; Washington, DC: 2011
28	Cho KA, Kim JY, Kim HS, Ryu KH and Woo SY: Tonsil-derived mesenchymal progenitor cells acquire a follicular dendritic cell phenotype under cytokine stimulation. Cytokine. 59:211–214. 2012. View Article : Google Scholar : PubMed/NCBI
29	D'Hooge R, Hartmann D, Manil J, Colin F, Gieselmann V and De Deyn PP: Neuromotor alterations and cerebellar deficits in aged arylsulfatase A-deficient transgenic mice. Neurosci Lett. 273:93–96. 1999. View Article : Google Scholar : PubMed/NCBI
30	Fernagut PO, Diguet E, Labattu B and Tison F: A simple method to measure stride length as an index of nigrostriatal dysfunction in mice. J Neurosci Methods. 113:123–130. 2002. View Article : Google Scholar : PubMed/NCBI
31	Beattie GM, Lopez AD, Bucay N, Hinton A, Firpo MT, King CC and Hayek A: Activin A maintains pluripotency of human embryonic stem cells in the absence of feeder layers. Stem Cells. 23:489–495. 2005. View Article : Google Scholar : PubMed/NCBI
32	Carpenter MK, Rosler ES, Fisk GJ, Brandenberger R, Ares X, Miura T, Lucero M and Rao MS: Properties of four human embryonic stem cell lines maintained in a feeder-free culture system. Dev Dyn. 229:243–258. 2004. View Article : Google Scholar : PubMed/NCBI
33	Nakatake Y, Fukui N, Iwamatsu Y, Masui S, Takahashi K, Yagi R, Yagi K, Miyazaki J, Matoba R, Ko MS and Niwa H: Klf4 cooperates with Oct3/4 and Sox2 to activate the Lefty1 core promoter in embryonic stem cells. Mol Cell Biol. 26:7772–7782. 2006. View Article : Google Scholar : PubMed/NCBI
34	Ropka-Molik K, Eckert R and Piórkowska K: The expression pattern of myogenic regulatory factors MyoD, Myf6 and Pax7 in postnatal porcine skeletal muscles. Gene Expr Patterns. 11:79–83. 2011. View Article : Google Scholar
35	García-Pelagio KP, Bloch RJ, Ortega A and González-Serratos H: Biomechanics of the sarcolemma and costameres in single skeletal muscle fibers from normal and dystrophin-null mice. J Muscle Res Cell Motil. 31:323–336. 2011. View Article : Google Scholar : PubMed/NCBI
36	Hass R, Kasper C, Böhm S and Jacobs R: Different populations and sources of human mesenchymal stem cells (MSC): a comparison of adult and neonatal tissue-derived MSC. Cell Commun Signal. 9:122011. View Article : Google Scholar : PubMed/NCBI
37	Böttcher-Haberzeth S, Biedermann T, Klar AS, Pontiggia L, Rac J, Nadal D, Schiestl C, Reichmann E and Meuli M: Tissue engineering of skin: human tonsil-derived mesenchymal cells can function as dermal fibroblasts. Pediatr Surg Int. 30:213–222. 2014. View Article : Google Scholar
38	Choy L, Skillington J and Derynck R: Roles of autocrine TGF-beta receptor and Smad signaling in adipocyte differentiation. J Cell Biol. 149:667–682. 2000. View Article : Google Scholar : PubMed/NCBI
39	Ignotz RA and Massagué J: Type beta transforming growth factor controls the adipogenic differentiation of 3T3 fibroblasts. Proc Natl Acad Sci USA. 82:8530–8534. 1985. View Article : Google Scholar : PubMed/NCBI
40	Centrella M, Horowitz MC, Wozney JM and McCarthy TL: Transforming growth factor-beta gene family members and bone. Endocr Rev. 15:27–39. 1994.PubMed/NCBI
41	Olson EN: Proto-oncogenes in the regulatory circuit for myogenesis. Semin Cell Biol. 3:127–136. 1992. View Article : Google Scholar : PubMed/NCBI
42	Massagué J, Cheifetz S, Endo T and Nadal-Ginard B: Type beta transforming growth factor is an inhibitor of myogenic differentiation. Proc Natl Acad Sci USA. 83:8206–8210. 1986. View Article : Google Scholar : PubMed/NCBI
43	Olson EN, Sternberg E, Hu JS, Spizz G and Wilcox C: Regulation of myogenic differentiation by type beta transforming growth factor. J Cell Biol. 103:1799–1805. 1986. View Article : Google Scholar : PubMed/NCBI
44	Sordella R, Jiang W, Chen GC, Curto M and Settleman J: Modulation of Rho GTPase signaling regulates a switch between adipogenesis and myogenesis. Cell. 113:147–158. 2003. View Article : Google Scholar : PubMed/NCBI
45	Schiaffino S and Mammucari C: Regulation of skeletal muscle growth by the IGF1-Akt/PKB pathway: insights from genetic models. Skelet Muscle. 1:42011. View Article : Google Scholar : PubMed/NCBI
46	Zdanowicz MM, Moyse J, Wingertzahn MA, O'Connor M, Teichberg S and Slonim AE: Effect of insulin-like growth factor I in murine muscular dystrophy. Endocrinology. 136:4880–4886. 1995.PubMed/NCBI
47	Jones JI and Clemmons DR: Insulin-like growth factors and their binding proteins: biological actions. Endocr Rev. 16:3–34. 1995.PubMed/NCBI
48	Bassaglia Y and Gautron J: Fast and slow rat muscles degenerate and regenerate differently after whole crush injury. J Muscle Res Cell Motil. 16:420–429. 1995. View Article : Google Scholar : PubMed/NCBI
49	Dedkov EI, Kostrominova TY, Borisov AB and Carlson BM: Reparative myogenesis in long-term denervated skeletal muscles of adult rats results in a reduction of the satellite cell population. Anat Rec. 263:139–154. 2001. View Article : Google Scholar : PubMed/NCBI
50	Politi PK, Havaki S, Manta P and Lyritis G: Bupivacaine-induced regeneration of rat soleus muscle: ultrastructural and immunohistochemical aspects. Ultrastruct Pathol. 30:461–469. 2006. View Article : Google Scholar : PubMed/NCBI
51	Merritt EK, Hammers DW, Tierney M, Suggs LJ, Walters TJ and Farrar RP: Functional assessment of skeletal muscle regeneration utilizing homologous extracellular matrix as scaffolding. Tissue Eng Part A. 16:1395–1405. 2010. View Article : Google Scholar