Skip to main content

Advertisement

SpringerLink
Log in

Dopaminergic Neuronal Conversion from Adult Rat Skeletal Muscle-Derived Stem Cells In Vitro

  • Original Paper
  • Published:
Neurochemical Research Aims and scope Submit manuscript

Abstract

Muscle-derived stem cells reside in the skeletal muscle tissues and are known for their multipotency to differentiate toward the mesodermal lineage. Recent studies have demonstrated their capacity of neuroectodermal differentiation, including neurons and astrocytes. In this study, we investigated the possibility of dopaminergic neuronal conversion from adult rat skeletal muscle-derived stem cells. Using a neurosphere protocol, muscle-derived stem cells form neurosphere-like cell clusters after cultivation as a suspension, displaying an obvious expression of nestin and a remarkable down-regulation of myogenic associated factors desmin, MyoD, Myf5 and myogenin. Subsequently, these neurosphere-like cell clusters were further directed to dopaminergic differentiation through two major induction steps, patterning to midbrain progenitors with sonic hedgehog and fibroblast growth factor 8, followed by the differentiation to dopaminergic neurons with neurotrophic factors (glial cell line-derived neurotrophic factor) and chemicals (ascorbic acid, forskolin). After the differentiation, these cells expressed tyrosine hydroxylase, dopamine transporter, dopamine D1 receptor and synapse-associated protein synapsin I. Several genes, Nurr1, Lmx1b, and En1, which are critically related with the development of dopaminergic neurons, were also significantly up-regulated. The present results indicate that adult skeletal muscle-derived stem cells could provide a promising cell source for autologous transplantation for neurodegenerative diseases in the future, especially the Parkinson’s disease.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3
Fig. 4

Similar content being viewed by others

References

  1. Collins CA, Olsen I, Zammit PS, Heslop L, Petrie A, Partridge TA, Morgan JE (2005) Stem cell function, self-renewal, and behavioral heterogeneity of cells from the adult muscle satellite cell niche. Cell 122(2):289–301

    Article  PubMed  CAS  Google Scholar 

  2. Morgan JE, Partridge TA (2003) Muscle satellite cells. Int J Biochem Cell Biol 35(8):1151–1156

    Article  PubMed  CAS  Google Scholar 

  3. Deasy BM, Gharaibeh BM, Pollett JB, Jones MM, Lucas MA, Kanda Y, Huard J (2005) Long-term self-renewal of postnatal muscle-derived stem cells. Mol Biol Cell 16(7):3323–3333

    Article  PubMed  CAS  Google Scholar 

  4. Usas A, Maciulaitis J, Maciulaitis R, Jakuboniene N, Milasius A, Huard J (2011) Skeletal muscle-derived stem cells: implications for cell-mediated therapies. Medicina (Kaunas) 47(9):469–479

    Google Scholar 

  5. Deasy BM, Jankowski RJ, Huard J (2001) Muscle-derived stem cells: characterization and potential for cell-mediated therapy. Blood Cells Mol Dis 27(5):924–933

    Article  PubMed  CAS  Google Scholar 

  6. Huard J, Cao B, Qu-Petersen Z (2003) Muscle-derived stem cells: potential for muscle regeneration. Birth Defects Res C Embryo Today 69(3):230–237

    Article  PubMed  CAS  Google Scholar 

  7. Aguiari P, Leo S, Zavan B, Vindigni V, Rimessi A, Bianchi K, Franzin C, Cortivo R, Rossato M, Vettor R, Abatangelo G, Pozzan T, Pinton P, Rizzuto R (2008) High glucose induces adipogenic differentiation of muscle-derived stem cells. Proc Natl Acad Sci USA 105(4):1226–1231

    Article  PubMed  CAS  Google Scholar 

  8. Sun JS, Wu SY, Lin FH (2005) The role of muscle-derived stem cells in bone tissue engineering. Biomaterials 26(18):3953–3960

    Article  PubMed  CAS  Google Scholar 

  9. Ye C, Li J, He Z, Nin X, Zhang Y, Shang X, Liu R, Duan Y (2010) Multilineage differentiation of muscle-derived stem cells from GFP transgenic mice. Biotechnol Lett 32(11):1745–1752

    Article  PubMed  CAS  Google Scholar 

  10. Oswald J, Boxberger S, Jorgensen B, Feldmann S, Ehninger G, Bornhauser M, Werner C (2004) Mesenchymal stem cells can be differentiated into endothelial cells in vitro. Stem Cells 22(3):377–384

    Article  PubMed  Google Scholar 

  11. Arriero M, Brodsky SV, Gealekman O, Lucas PA, Goligorsky MS (2004) Adult skeletal muscle stem cells differentiate into endothelial lineage and ameliorate renal dysfunction after acute ischemia. Am J Physiol Renal Physiol 287(4):F621–F627

    Article  PubMed  CAS  Google Scholar 

  12. Bellayr IH, Gharaibeh B, Huard J, Li Y (2010) Skeletal muscle-derived stem cells differentiate into hepatocyte-like cells and aid in liver regeneration. Int J Clin Exp Pathol 3(7):681–690

    PubMed  CAS  Google Scholar 

  13. Cao B, Zheng B, Jankowski RJ, Kimura S, Ikezawa M, Deasy B, Cummins J, Epperly M, Qu-Petersen Z, Huard J (2003) Muscle stem cells differentiate into haematopoietic lineages but retain myogenic potential. Nat Cell Biol 5(7):640–646

    Article  PubMed  CAS  Google Scholar 

  14. Farace F, Prestoz L, Badaoui S, Guillier M, Haond C, Opolon P, Thomas JL, Zalc B, Vainchenker W, Turhan AG (2004) Evaluation of hematopoietic potential generated by transplantation of muscle-derived stem cells in mice. Stem Cells Dev 13(1):83–92

    Article  PubMed  CAS  Google Scholar 

  15. Arsic N, Mamaeva D, Lamb NJ, Fernandez A (2008) Muscle-derived stem cells isolated as non-adherent population give rise to cardiac, skeletal muscle and neural lineages. Exp Cell Res 314(6):1266–1280

    Article  PubMed  CAS  Google Scholar 

  16. Kim ES, Kim GH, Kang ML, Kang YM, Kang KN, Hwang KC, Min BH, Kim JH, Kim MS (2011) Potential induction of rat muscle-derived stem cells to neural-like cells by retinoic acid. J Tissue Eng Regen Med 5(5):410–414

    Article  PubMed  CAS  Google Scholar 

  17. Alessandri G, Pagano S, Bez A, Benetti A, Pozzi S, Iannolo G, Baronio M, Invernici G, Caruso A, Muneretto C, Bisleri G, Parati E (2004) Isolation and culture of human muscle-derived stem cells able to differentiate into myogenic and neurogenic cell lineages. Lancet 364(9448):1872–1883

    Article  PubMed  CAS  Google Scholar 

  18. Kondo T, Case J, Srour EF, Hashino E (2006) Skeletal muscle-derived progenitor cells exhibit neural competence. NeuroReport 17(1):1–4

    Article  PubMed  Google Scholar 

  19. Tamaki T, Okada Y, Uchiyama Y, Tono K, Masuda M, Wada M, Hoshi A, Ishikawa T, Akatsuka A (2007) Clonal multipotency of skeletal muscle-derived stem cells between mesodermal and ectodermal lineage. Stem Cells 25(9):2283–2290

    Article  PubMed  CAS  Google Scholar 

  20. Anwar MR, Andreasen CM, Lippert SK, Zimmer J, Martinez-Serrano A, Meyer M (2008) Dopaminergic differentiation of human neural stem cells mediated by co-cultured rat striatal brain slices. J Neurochem 105(2):460–470

    Article  PubMed  CAS  Google Scholar 

  21. Cho MS, Hwang DY, Kim DW (2008) Efficient derivation of functional dopaminergic neurons from human embryonic stem cells on a large scale. Nat Protoc 3(12):1888–1894

    Article  PubMed  CAS  Google Scholar 

  22. Bjorklund LM, Sanchez-Pernaute R, Chung S, Andersson T, Chen IY, McNaught KS, Brownell AL, Jenkins BG, Wahlestedt C, Kim KS, Isacson O (2002) Embryonic stem cells develop into functional dopaminergic neurons after transplantation in a Parkinson rat model. Proc Natl Acad Sci USA 99(4):2344–2349

    Article  PubMed  CAS  Google Scholar 

  23. Wang X, Li X, Wang K, Zhou H, Xue B, Li L (2004) Forskolin cooperating with growth factor on generation of dopaminergic neurons from human fetal mesencephalic neural progenitor cells. Neurosci Lett 362(2):117–121

    Article  PubMed  CAS  Google Scholar 

  24. Barzilay R, Kan I, Ben-Zur T, Bulvik S, Melamed E, Offen D (2008) Induction of human mesenchymal stem cells into dopamine-producing cells with different differentiation protocols. Stem Cells Dev 17(3):547–554

    Article  PubMed  CAS  Google Scholar 

  25. Sanchez-Danes A, Richaud-Patin Y, Carballo-Carbajal I, Jimenez-Delgado S, Caig C, Mora S, Di Guglielmo C, Ezquerra M, Patel B, Giralt A, Canals JM, Memo M, Alberch J, Lopez-Barneo J, Vila M, Cuervo AM, Tolosa E, Consiglio A, Raya A (2012) Disease-specific phenotypes in dopamine neurons from human iPS-based models of genetic and sporadic Parkinson’s disease. EMBO Mol Med 4(5):380–395

    Article  PubMed  CAS  Google Scholar 

  26. Swistowski A, Peng J, Liu Q, Mali P, Rao MS, Cheng L, Zeng X (2010) Efficient generation of functional dopaminergic neurons from human induced pluripotent stem cells under defined conditions. Stem Cells 28(10):1893–1904

    Article  PubMed  CAS  Google Scholar 

  27. Fong CY, Gauthaman K, Bongso A (2010) Teratomas from pluripotent stem cells: a clinical hurdle. J Cell Biochem 111(4):769–781

    Article  PubMed  CAS  Google Scholar 

  28. Kawai H, Yamashita T, Ohta Y, Deguchi K, Nagotani S, Zhang X, Ikeda Y, Matsuura T, Abe K (2010) Tridermal tumorigenesis of induced pluripotent stem cells transplanted in ischemic brain. J Cereb Blood Flow Metab 30(8):1487–1493

    Article  PubMed  Google Scholar 

  29. Romero-Ramos M, Vourc’h P, Young HE, Lucas PA, Wu Y, Chivatakarn O, Zaman R, Dunkelman N, el-Kalay MA, Chesselet MF (2002) Neuronal differentiation of stem cells isolated from adult muscle. J Neurosci Res 69(6):894–907

    Article  PubMed  CAS  Google Scholar 

  30. Rando TA, Blau HM (1994) Primary mouse myoblast purification, characterization, and transplantation for cell-mediated gene therapy. J Cell Biol 125(6):1275–1287

    Article  PubMed  CAS  Google Scholar 

  31. Shen JL, Huang YZ, Xu SX, Zheng PH, Yin WJ, Cen J, Gong LZ (2012) Effectiveness of human mesenchymal stem cells derived from bone marrow cryopreserved for 23–25 years. Cryobiology (Epub ahead of print)

  32. Tsai MS, Lee JL, Chang YJ, Hwang SM (2004) Isolation of human multipotent mesenchymal stem cells from second-trimester amniotic fluid using a novel two-stage culture protocol. Hum Reprod 19(6):1450–1456

    Article  PubMed  Google Scholar 

  33. Jackson KA, Mi T, Goodell MA (1999) Hematopoietic potential of stem cells isolated from murine skeletal muscle. Proc Natl Acad Sci USA 96(25):14482–14486

    Article  PubMed  CAS  Google Scholar 

  34. Telford WG, Bradford J, Godfrey W, Robey RW, Bates SE (2007) Side population analysis using a violet-excited cell-permeable DNA binding dye. Stem Cells 25(4):1029–1036

    Article  PubMed  CAS  Google Scholar 

  35. Asakura A, Rudnicki MA (2002) Side population cells from diverse adult tissues are capable of in vitro hematopoietic differentiation. Exp Hematol 30(11):1339–1345

    Article  PubMed  Google Scholar 

  36. Zhou S, Schuetz JD, Bunting KD, Colapietro AM, Sampath J, Morris JJ, Lagutina I, Grosveld GC, Osawa M, Nakauchi H, Sorrentino BP (2001) The ABC transporter Bcrp1/ABCG2 is expressed in a wide variety of stem cells and is a molecular determinant of the side-population phenotype. Nat Med 7(9):1028–1034

    Article  PubMed  CAS  Google Scholar 

  37. Kachinsky AM, Dominov JA, Miller JB (1994) Myogenesis and the intermediate filament protein, nestin. Dev Biol 165(1):216–228

    Article  PubMed  CAS  Google Scholar 

  38. Lee SH, Lumelsky N, Studer L, Auerbach JM, McKay RD (2000) Efficient generation of midbrain and hindbrain neurons from mouse embryonic stem cells. Nat Biotechnol 18(6):675–679

    Article  PubMed  CAS  Google Scholar 

  39. Ye W, Shimamura K, Rubenstein JL, Hynes MA, Rosenthal A (1998) FGF and Shh signals control dopaminergic and serotonergic cell fate in the anterior neural plate. Cell 93(5):755–766

    Article  PubMed  CAS  Google Scholar 

  40. Jankovic J, Chen S, Le WD (2005) The role of Nurr1 in the development of dopaminergic neurons and Parkinson’s disease. Prog Neurobiol 77(1–2):128–138

    Article  PubMed  CAS  Google Scholar 

  41. Vourc’h P, Romero-Ramos M, Chivatakarn O, Young HE, Lucas PA, El-Kalay M, Chesselet MF (2004) Isolation and characterization of cells with neurogenic potential from adult skeletal muscle. Biochem Biophys Res Commun 317(3):893–901

    Article  PubMed  Google Scholar 

  42. Wu X, Wang S, Chen B, An X (2010) Muscle-derived stem cells: isolation, characterization, differentiation, and application in cell and gene therapy. Cell Tissue Res 340(3):549–567

    Article  PubMed  Google Scholar 

  43. Baek YS, Kang SH, Park JS, Kim S, Yoo BS, Lee JY, Ghil SH (2009) Long-term cultured skeletal muscle-derived neural precursor cells and their neurogenic potentials. NeuroReport 20(12):1109–1114

    PubMed  Google Scholar 

  44. Lawson-Smith MJ, McGeachie JK (1998) The identification of myogenic cells in skeletal muscle, with emphasis on the use of tritiated thymidine autoradiography and desmin antibodies. J Anat 192(Pt 2):161–171

    Article  PubMed  Google Scholar 

  45. Gal-Levi R, Leshem Y, Aoki S, Nakamura T, Halevy O (1998) Hepatocyte growth factor plays a dual role in regulating skeletal muscle satellite cell proliferation and differentiation. Biochim Biophys Acta 1402(1):39–51

    Article  PubMed  CAS  Google Scholar 

  46. Irintchev A, Zeschnigk M, Starzinski-Powitz A, Wernig A (1994) Expression pattern of M-cadherin in normal, denervated, and regenerating mouse muscles. Dev Dyn 199(4):326–337

    Article  PubMed  CAS  Google Scholar 

  47. Cooper RN, Tajbakhsh S, Mouly V, Cossu G, Buckingham M, Butler-Browne GS (1999) In vivo satellite cell activation via Myf5 and MyoD in regenerating mouse skeletal muscle. J Cell Sci 112(Pt 17):2895–2901

    PubMed  CAS  Google Scholar 

  48. Lendahl U, Zimmerman LB, McKay RD (1990) CNS stem cells express a new class of intermediate filament protein. Cell 60(4):585–595

    Article  PubMed  CAS  Google Scholar 

  49. Shefer G, Wleklinski-Lee M, Yablonka-Reuveni Z (2004) Skeletal muscle satellite cells can spontaneously enter an alternative mesenchymal pathway. J Cell Sci 117(Pt 22):5393–5404

    Article  PubMed  CAS  Google Scholar 

  50. Svendsen CN, ter Borg MG, Armstrong RJ, Rosser AE, Chandran S, Ostenfeld T, Caldwell MA (1998) A new method for the rapid and long term growth of human neural precursor cells. J Neurosci Methods 85(2):141–152

    Article  PubMed  CAS  Google Scholar 

  51. Kim JH, Auerbach JM, Rodriguez-Gomez JA, Velasco I, Gavin D, Lumelsky N, Lee SH, Nguyen J, Sanchez-Pernaute R, Bankiewicz K, McKay R (2002) Dopamine neurons derived from embryonic stem cells function in an animal model of Parkinson’s disease. Nature 418(6893):50–56

    Article  PubMed  CAS  Google Scholar 

  52. Laywell ED, Kukekov VG, Steindler DA (1999) Multipotent neurospheres can be derived from forebrain subependymal zone and spinal cord of adult mice after protracted postmortem intervals. Exp Neurol 156(2):430–433

    Article  PubMed  CAS  Google Scholar 

  53. Neumeister B, Grabosch A, Basak O, Kemler R, Taylor V (2009) Neural progenitors of the postnatal and adult mouse forebrain retain the ability to self-replicate, form neurospheres, and undergo multipotent differentiation in vivo. Stem Cells 27(3):714–723

    Article  PubMed  Google Scholar 

  54. Caldwell MA, He X, Wilkie N, Pollack S, Marshall G, Wafford KA, Svendsen CN (2001) Growth factors regulate the survival and fate of cells derived from human neurospheres. Nat Biotechnol 19(5):475–479

    Article  PubMed  CAS  Google Scholar 

  55. Vescovi AL, Parati EA, Gritti A, Poulin P, Ferrario M, Wanke E, Frolichsthal-Schoeller P, Cova L, Arcellana-Panlilio M, Colombo A, Galli R (1999) Isolation and cloning of multipotential stem cells from the embryonic human CNS and establishment of transplantable human neural stem cell lines by epigenetic stimulation. Exp Neurol 156(1):71–83

    Article  PubMed  CAS  Google Scholar 

  56. Chen X, Mao Z, Liu S, Liu H, Wang X, Wu H, Wu Y, Zhao T, Fan W, Li Y, Yew DT, Kindler PM, Li L, He Q, Qian L, Fan M (2005) Dedifferentiation of adult human myoblasts induced by ciliary neurotrophic factor in vitro. Mol Biol Cell 16(7):3140–3151

    Article  PubMed  CAS  Google Scholar 

  57. Riazi AM, Lee H, Hsu C, Van Arsdell G (2005) CSX/Nkx2.5 modulates differentiation of skeletal myoblasts and promotes differentiation into neuronal cells in vitro. J Biol Chem 280(11):10716–10720

    Article  PubMed  CAS  Google Scholar 

  58. Smidt MP, Burbach JP (2007) How to make a mesodiencephalic dopaminergic neuron. Nat Rev Neurosci 8(1):21–32

    Article  PubMed  CAS  Google Scholar 

  59. Prakash N, Wurst W (2006) Development of dopaminergic neurons in the mammalian brain. Cell Mol Life Sci 63(2):187–206

    Article  PubMed  CAS  Google Scholar 

  60. Simon HH, Bhatt L, Gherbassi D, Sgado P, Alberi L (2003) Midbrain dopaminergic neurons: determination of their developmental fate by transcription factors. Ann NY Acad Sci 991:36–47

    Article  PubMed  CAS  Google Scholar 

  61. Schultz SS, Lucas PA (2006) Human stem cells isolated from adult skeletal muscle differentiate into neural phenotypes. J Neurosci Methods 152(1–2):144–155

    Article  PubMed  CAS  Google Scholar 

Download references

Acknowledgments

This work was supported by grants from the Chinese National Basic Research 973 Program (2011CB504100, 2010CB944801) and National Science Foundation of Beijing (5102010). We thank Dr. Yang Li for critical reading of the manuscript.

Author information

Authors and Affiliations

  1. Key Laboratory for Neurodegenerative Disease of Education Ministry, Department of Physiology and Neurobiology, Capital Medical University, 10# Youanmen, Beijing, 100069, People’s Republic of China

    Jian Yang, Xuan Wang, Yue Wang, Zi-Xuan Guo, Ding-Zhen Luo, Jun Jia & Xiao-Min Wang

Authors
  1. Jian Yang
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Xuan Wang
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Yue Wang
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Zi-Xuan Guo
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Ding-Zhen Luo
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Jun Jia
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Xiao-Min Wang
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Xiao-Min Wang.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Yang, J., Wang, X., Wang, Y. et al. Dopaminergic Neuronal Conversion from Adult Rat Skeletal Muscle-Derived Stem Cells In Vitro. Neurochem Res 37, 1982–1992 (2012). https://doi.org/10.1007/s11064-012-0819-9

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s11064-012-0819-9

Keywords

Search

Navigation