Skip to main content

Advertisement

SpringerLink
Log in

Human muscular fetal cells: a potential cell source for muscular therapies

  • Original Article
  • Published:
Pediatric Surgery International Aims and scope Submit manuscript

Abstract

Myoblast transfer therapy has been extensively studied for a wide range of clinical applications, such as tissue engineering for muscular loss, cardiac surgery or Duchenne Muscular Dystrophy treatment. However, this approach has been hindered by numerous limitations, including early myoblast death after injection and specific immune response after transplantation with allogenic cells. Different cell sources have been analyzed to overcome some of these limitations. The object of our study was to investigate the growth potential, characterization and integration in vivo of human primary fetal skeletal muscle cells. These data together show the potential for the creation of a cell bank to be used as a cell source for muscle cell therapy and tissue engineering. For this purpose, we developed primary muscular cell cultures from biopsies of human male thigh muscle from a 16-week-old fetus and from donors of 13 and 30 years old. We show that fetal myogenic cells can be successfully isolated and expanded in vitro from human fetal muscle biopsies, and that fetal cells have higher growth capacities when compared to young and adult cells. We confirm lineage specificity by comparing fetal muscle cells to fetal skin and bone cells in vitro by immunohistochemistry with desmin and 5.1H11 antibodies. For the feasibility of the cell bank, we ensured that fetal muscle cells retained intrinsic characteristics after 5 years cryopreservation. Finally, human fetal muscle cells marked with PKH26 were injected in normal C57BL/6 mice and were found to be present up to 4 days. In conclusion we estimate that a human fetal skeletal muscle cell bank can be created for potential muscle cell therapy and tissue engineering.

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
Fig. 5
Fig. 6
Fig. 7
Fig. 8

Similar content being viewed by others

References

  1. Partridge T (2002) Myoblast transplantation. Neuromuscul Disord 12(Suppl 1):S3–S6

    Article  PubMed  Google Scholar 

  2. Skuk D, Tremblay JP (2000) Progress in myoblast transplantation: a potential treatment of dystrophies. Microsc Res Tech 48:213–222

    Article  PubMed  CAS  Google Scholar 

  3. Skuk D, Vilquin JT, Tremblay JP (2002) Experimental and therapeutic approaches to muscular dystrophies. Curr Opin Neurol 15:563–569

    Article  PubMed  Google Scholar 

  4. Skuk D, Tremblay JP (2003) Myoblast transplantation: the current status of a potential therapeutic tool for myopathies. J Muscle Res Cell Motil 24:285–300

    Article  PubMed  CAS  Google Scholar 

  5. Menasche P (2005) Skeletal myoblast for cell therapy. Coron Artery Dis 16:105–110

    Article  PubMed  Google Scholar 

  6. Huard J, Li Y, Fu FH (2002) Muscle injuries and repair: current trends in research. J Bone Joint Surg Am 84-A:822–832

    PubMed  Google Scholar 

  7. Partridge T (2002) Myoblast transplantation. Neuromuscul Disord 12(Suppl 1):S3–S6

    Article  PubMed  Google Scholar 

  8. Partridge TA, Grounds M, Sloper JC (1978) Evidence of fusion between host and donor myoblasts in skeletal muscle grafts. Nature 273:306–308

    Article  PubMed  CAS  Google Scholar 

  9. Menasche P (2005) Skeletal myoblast for cell therapy. Coron Artery Dis 16:105–110

    Article  PubMed  Google Scholar 

  10. Partridge TA, Grounds M, Sloper JC (1978) Evidence of fusion between host and donor myoblasts in skeletal muscle grafts. Nature 273:306–308

    Article  PubMed  CAS  Google Scholar 

  11. Skuk D, Roy B, Goulet M, Tremblay JP (1999) Successful myoblast transplantation in primates depends on appropriate cell delivery and induction of regeneration in the host muscle. Exp Neurol 155:22–30

    Article  PubMed  CAS  Google Scholar 

  12. Partridge T (2002) Myoblast transplantation. Neuromuscul Disord 12(Suppl 1):S3–S6

    Article  PubMed  Google Scholar 

  13. Skuk D, Tremblay JP (2000) Progress in myoblast transplantation: a potential treatment of dystrophies. Microsc Res Tech 48:213–222

    Article  PubMed  CAS  Google Scholar 

  14. Partridge T (2002) Myoblast transplantation. Neuromuscul Disord 12(Suppl 1):S3–S6

    Article  PubMed  Google Scholar 

  15. Smythe GM, Hodgetts SI, Grounds MD (2000) Immunobiology and the future of myoblast transfer therapy. Mol Ther 1:304–313

    Article  PubMed  CAS  Google Scholar 

  16. Beauchamp JR, Pagel CN, Partridge TA (1997) A dual-marker system for quantitative studies of myoblast transplantation in the mouse. Transplantation 63:1794–1797

    Article  PubMed  CAS  Google Scholar 

  17. Beauchamp JR, Morgan JE, Pagel CN, Partridge TA (1999) Dynamics of myoblast transplantation reveal a discrete minority of precursors with stem cell-like properties as the myogenic source. J Cell Biol 144:1113–1122

    Article  PubMed  CAS  Google Scholar 

  18. Fan Y, Maley M, Beilharz M, Grounds M (1996) Rapid death of injected myoblasts in myoblast transfer therapy. Muscle Nerve 19:853–860

    Article  PubMed  CAS  Google Scholar 

  19. Hodgetts SI, Beilharz MW, Scalzo AA, Grounds MD (2000) Why do cultured transplanted myoblasts die in vivo? DNA quantification shows enhanced survival of donor male myoblasts in host mice depleted of CD4+ and CD8+ cells or Nk1.1+ cells. Cell Transplant 9:489–502

    PubMed  CAS  Google Scholar 

  20. Hodgetts SI, Spencer MJ, Grounds MD (2003) A role for natural killer cells in the rapid death of cultured donor myoblasts after transplantation. Transplantation 75:863–871

    Article  PubMed  Google Scholar 

  21. Qu Z, Balkir L, van Deutekom JC, Robbins PD, Pruchnic R, Huard J (1998) Development of approaches to improve cell survival in myoblast transfer therapy. J Cell Biol 142:1257–1267

    Article  PubMed  CAS  Google Scholar 

  22. Rando TA, Pavlath GK, Blau HM (1995) The fate of myoblasts following transplantation into mature muscle. Exp Cell Res 220:383–389

    Article  PubMed  CAS  Google Scholar 

  23. Sammels LM, Bosio E, Fragall CT, Grounds MD, van Rooijen N, Beilharz MW (2004) Innate inflammatory cells are not responsible for early death of donor myoblasts after myoblast transfer therapy. Transplantation 77:1790–1797

    Article  PubMed  Google Scholar 

  24. Fan Y, Maley M, Beilharz M, Grounds M (1996) Rapid death of injected myoblasts in myoblast transfer therapy. Muscle Nerve 19:853–860

    Article  PubMed  CAS  Google Scholar 

  25. Hodgetts SI, Beilharz MW, Scalzo AA, Grounds MD (2000) Why do cultured transplanted myoblasts die in vivo? DNA quantification shows enhanced survival of donor male myoblasts in host mice depleted of CD4+ and CD8+ cells or Nk1.1+ cells. Cell Transplant 9:489–502

    PubMed  CAS  Google Scholar 

  26. Tambara K, Sakakibara Y, Sakaguchi G, Lu F, Premaratne GU, Lin X, Nishimura K, Komeda M (2003) Transplanted skeletal myoblasts can fully replace the infarcted myocardium when they survive in the host in large numbers. Circulation 108(Suppl 1):II259–II263

    PubMed  Google Scholar 

  27. Qu Z, Balkir L, van Deutekom JC, Robbins PD, Pruchnic R, Huard J (1998) Development of approaches to improve cell survival in myoblast transfer therapy. J Cell Biol 142:1257–1267

    Article  PubMed  CAS  Google Scholar 

  28. Pavlath GK, Rando TA, Blau HM (1994) Transient immunosuppressive treatment leads to long-term retention of allogeneic myoblasts in hybrid myofibers. J Cell Biol 127:1923–1932

    Article  PubMed  CAS  Google Scholar 

  29. Guerette B, Skuk D, Celestin F, Huard C, Tardif F, Asselin I, Roy B, Goulet M, Roy R, Entman M, Tremblay JP (1997) Prevention by anti-LFA-1 of acute myoblast death following transplantation. J Immunol 159:2522–2531

    PubMed  CAS  Google Scholar 

  30. Dellavalle A, Sampaolesi M, Tonlorenzi R, Tagliafico E, Sacchetti B, Perani L, Innocenzi A, Galvez BG, Messina G, Morosetti R, Li S, Belicchi M, Peretti G, Chamberlain JS, Wright WE, Torrente Y, Ferrari S, Bianco P, Cossu G (2007) Pericytes of human skeletal muscle are myogenic precursors distinct from satellite cells. Nat Cell Biol 9:255–267

    Article  PubMed  CAS  Google Scholar 

  31. Maurel A, Azarnoush K, Sabbah L, Vignier N, Le Lorc’h M, Mandet C, Bissery A, Garcin I, Carrion C, Fiszman M, Bruneval P, Hagege A, Carpentier A, Vilquin JT, Menasche P (2005) Can cold or heat shock improve skeletal myoblast engraftment in infarcted myocardium? Transplantation 80:660–665

    Article  PubMed  Google Scholar 

  32. Qu Z, Balkir L, van Deutekom JC, Robbins PD, Pruchnic R, Huard J (1998) Development of approaches to improve cell survival in myoblast transfer therapy. J Cell Biol 142:1257–1267

    Article  PubMed  CAS  Google Scholar 

  33. Jankowski RJ, Haluszczak C, Trucco M, Huard J (2001) Flow cytometric characterization of myogenic cell populations obtained via the preplate technique: potential for rapid isolation of muscle-derived stem cells. Hum Gene Ther 12:619–628

    Article  PubMed  CAS  Google Scholar 

  34. Huard J, Verreault S, Roy R, Tremblay M, Tremblay JP (1994) High efficiency of muscle regeneration after human myoblast clone transplantation in SCID mice. J Clin Invest 93:586–599

    PubMed  CAS  Google Scholar 

  35. Torrente Y, Tremblay JP, Pisati F, Belicchi M, Rossi B, Sironi M, Fortunato F, El Fahime M, D’Angelo MG, Caron NJ, Constantin G, Paulin D, Scarlato G, Bresolin N (2001) Intraarterial injection of muscle-derived CD34(+)Sca-1(+) stem cells restores dystrophin in mdx mice. J Cell Biol 152:335–348

    Article  PubMed  CAS  Google Scholar 

  36. Vats A, Bielby RC, Tolley NS, Nerem R, Polak JM (2005) Stem cells. Lancet 366:592–602

    Article  PubMed  CAS  Google Scholar 

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

    Article  PubMed  CAS  Google Scholar 

  38. Orlic D, Kajstura J, Chimenti S, Jakoniuk I, Anderson SM, Li B, Pickel J, McKay R, Nadal-Ginard B, Bodine DM, Leri A, Anversa P (2001) Bone marrow cells regenerate infarcted myocardium. Nature 410:701–705

    Article  PubMed  CAS  Google Scholar 

  39. De Coppi P, Bartsch G Jr, Siddiqui MM, Xu T, Santos CC, Perin L., Mostoslavsky G, Serre AC, Snyder EY, Yoo JJ, Furth ME, Soker S, Atala A (2007) Isolation of amniotic stem cell lines with potential for therapy. Nat Biotechnol 25:100–106

    Article  PubMed  CAS  Google Scholar 

  40. Gang EJ, Jeong JA, Hong SH, Hwang SH, Kim SW, Yang IH, Ahn C, Han H,Kim H (2004) Skeletal myogenic differentiation of mesenchymal stem cells isolated from human umbilical cord blood. Stem Cells 22:617–624

    Article  PubMed  Google Scholar 

  41. De Coppi P, Bartsch G Jr, Siddiqui MM, Xu T, Santos CC, Perin L., Mostoslavsky G, Serre AC, Snyder EY, Yoo JJ, Furth ME, Soker S, Atala A (2007) Isolation of amniotic stem cell lines with potential for therapy. Nat Biotechnol 25:100–106

    Article  PubMed  CAS  Google Scholar 

  42. Barry FP, Murphy JM (2004) Mesenchymal stem cells: clinical applications and biological characterization. Int J Biochem Cell Biol 36:568–584

    Article  PubMed  CAS  Google Scholar 

  43. Bullard KM, Longaker MT, Lorenz HP (2003) Fetal wound healing: current biology. World J Surg 27:54–61

    Article  PubMed  Google Scholar 

  44. Bhattacharya N (2004) Fetal cell/tissue therapy in adult disease: a new horizon in regenerative medicine. Clin Exp Obstet Gynecol 31:167–173

    PubMed  CAS  Google Scholar 

  45. Hohlfeld J, De Buys Roessingh AS, Hirt-Burri N, Chaubert P, Gerber S, Scaletta C, Hohlfeld P, Applegate LA (2005) Tissue engineered fetal skin constructs for paediatric burns. The Lancet 366:840–842

    Article  Google Scholar 

  46. Montjovent MO, Burri N, Mark S, Federici E, Scaletta C, Zambelli PY, Hohlfeld P, Leyvraz PF, Applegate LA, Pioletti DP (2004) Fetal bone cells for tissue engineering. Bone 35:1323–1333

    Article  PubMed  CAS  Google Scholar 

  47. De Buys Roessingh AS, Hohlfeld J, Scaletta C, Hirt-Burri N, Gerber S, Hohlfeld P, Gebbers JO,Applegate LA (2006) Development, characterization, and use of a fetal skin cell bank for tissue engineering in wound healing. Cell Transplant 15:823–834

    PubMed  Google Scholar 

  48. Crombleholme TM, Langer JC, Harrison MR, Zanjani ED (1991) Transplantation of fetal cells. Am J Obstet Gynecol 164:218–230

    PubMed  CAS  Google Scholar 

  49. Gabbianelli M, Boccoli G, Petti S, Cianetti L, La Valle R, Ferbus D, Mastroberardino G, Testa U, Peschle C (1987) Expression and in-vitro modulation of HLA antigens in ontogenic development of human hemopoietic system. Ann N Y Acad Sci 511:138–147

    Article  PubMed  CAS  Google Scholar 

  50. Clarkson ED (2001) Fetal tissue transplantation for patients with Parkinson’s disease: a database of published clinical results. Drugs Aging 18:773–785

    Article  PubMed  CAS  Google Scholar 

  51. Bachoud-Levi AC, Gaura V, Brugieres P, Lefaucheur JP, Boisse MF, Maison P, Baudic S, Ribeiro MJ, Bourdet C, Remy P, Cesaro P, Hantraye P, Peschanski M (2006) Effect of fetal neural transplants in patients with Huntington’s disease 6 years after surgery: a long-term follow-up study. Lancet Neurol 5:303–309

    Article  PubMed  Google Scholar 

  52. Peterson CM, Jovanovic-Peterson L, Formby B, Gondos B, Monda LM, Walker L, Rashbaum W, Williams K (1989) Human fetal pancreas transplants. J Diabet Complications 3:27–34

    Article  PubMed  CAS  Google Scholar 

  53. Pioletti DP, Montjovent MO, Zambelli PY, Applegate LA (2006) Bone tissue engineering using foetal cell therapy. Swiss Med Wkly 136:557–560

    PubMed  Google Scholar 

  54. Montjovent MO, Burri N, Mark S, Federici E, Scaletta C, Zambelli PY, Hohlfeld P, Leyvraz PF, Applegate LA, Pioletti DP (2004) Fetal bone cells for tissue engineering. Bone 35:1323–1333

    Article  PubMed  CAS  Google Scholar 

  55. Quintin A, Hirt-Burri N, Scaletta C, Schizas C, Pioletti DP, Applegate LA (2007) Consistency of fetal cell banks for research and clinical use. Cell Transplant (in press)

  56. Montjovent MO, Burri N, Mark S, Federici E, Scaletta C, Zambelli PY, Hohlfeld P, Leyvraz PF, Applegate LA, Pioletti DP (2004) Fetal bone cells for tissue engineering. Bone 35:1323–1333

    Article  PubMed  CAS  Google Scholar 

  57. Walsh FS, Ritter MA (1981) Surface antigen differentiation during human myogenesis in culture. Nature 289:60–64

    Article  PubMed  CAS  Google Scholar 

  58. Schafer R, Knauf U, Zweyer M, Hogemeier O, de Guarrini F, Liu X, Eichhorn HJ, Koch FW, Mundegar RR, Erzen I, Wernig A (2006) Age dependence of the human skeletal muscle stem cell in forming muscle tissue. Artif Organs 30:130–140

    Article  PubMed  Google Scholar 

  59. Schafer R, Knauf U, Zweyer M, Hogemeier O, de Guarrini F, Liu X, Eichhorn HJ, Koch FW, Mundegar RR, Erzen I, Wernig A (2006) Age dependence of the human skeletal muscle stem cell in forming muscle tissue. Artif Organs 30:130–140

    Article  PubMed  Google Scholar 

  60. Hodgetts SI, Beilharz MW, Scalzo AA, Grounds MD (2000) Why do cultured transplanted myoblasts die in vivo? DNA quantification shows enhanced survival of donor male myoblasts in host mice depleted of CD4+ and CD8+ cells or Nk1.1+ cells. Cell Transplant 9:489–502

    PubMed  CAS  Google Scholar 

  61. Fan Y, Beilharz MW, Grounds MD (1996) A potential alternative strategy for myoblast transfer therapy: the use of sliced muscle grafts. Cell Transplant 5:421–429

    Article  PubMed  CAS  Google Scholar 

  62. Tambara K, Sakakibara Y, Sakaguchi G, Lu F, Premaratne GU, Lin X, Nishimura K, Komeda M (2003) Transplanted skeletal myoblasts can fully replace the infarcted myocardium when they survive in the host in large numbers. Circulation 108(Suppl 1):II259–II263

    PubMed  Google Scholar 

  63. Sakai T, Li RK, Weisel RD, Mickle DA, Jia ZQ, Tomita S, Kim EJ, Yau TM (1999) Fetal cell transplantation: a comparison of three cell types. J Thorac Cardiovasc Surg 118:715–724

    Article  PubMed  CAS  Google Scholar 

  64. Decary S, Mouly V, Hamida CB, Sautet A, Barbet JP, Butler-Browne GS (1997) Replicative potential and telomere length in human skeletal muscle: implications for satellite cell-mediated gene therapy. Hum Gene Ther 8:1429–1438

    Article  PubMed  CAS  Google Scholar 

  65. Skuk D, Roy B, Goulet M, Chapdelaine P, Bouchard JP, Roy R, Dugre FJ, Lachance JG, Deschenes L, Helene S, Sylvain M, Tremblay JP (2004) Dystrophin expression in myofibers of Duchenne muscular dystrophy patients following intramuscular injections of normal myogenic cells. Mol Ther 9:475–482

    Article  PubMed  CAS  Google Scholar 

  66. Skuk D, Goulet M, Roy B, Piette V, Cote CH, Chapdelaine P, Hogrel JY, Paradis M, Bouchard JP, Sylvain M, Lachance JG, Tremblay JP (2007) First test of a “high-density injection” protocol for myogenic cell transplantation throughout large volumes of muscles in a Duchenne muscular dystrophy patient: eighteen months follow-up. Neuromuscul Disord 17:38–46

    Article  PubMed  Google Scholar 

Download references

Acknowledgment

We wish to thank the Dr. med. h.c. Erwin Braun Foundation for financing, in part, this study. We would thank A. Giraudeau-Christinat and O. Burri for their technical assistance.

Author information

Authors and Affiliations

  1. Pediatric Surgery Laboratory, University Hospital Lausanne, CHUV, CI/02/60, 1011, Lausanne, Switzerland

    Nathalie Hirt-Burri, Anthony S. de Buys Roessingh & Judith Hohlfeld

  2. Orthopedic Cell Therapy Unit, University Hospital Lausanne, Lausanne, Switzerland

    Corinne Scaletta & Lee Ann Applegate

  3. Department of Obstetrics, University Hospital Lausanne, Lausanne, Switzerland

    Stefan Gerber

  4. Laboratoire de Biomécanique en Orthopédie (EPFL-HORS), Institut de Biomécanique Translationnelle, Ecole Polytechnique Fédérale de Lausanne, Lausanne, Switzerland

    Corinne Scaletta, Dominique P. Pioletti & Lee Ann Applegate

Authors
  1. Nathalie Hirt-Burri
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Anthony S. de Buys Roessingh
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Corinne Scaletta
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Stefan Gerber
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Dominique P. Pioletti
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Lee Ann Applegate
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Judith Hohlfeld
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Nathalie Hirt-Burri.

Additional information

N. Hirt-Burri and A. S. de Buys Roessingh contributed equally to this work.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Hirt-Burri, N., de Buys Roessingh, A.S., Scaletta, C. et al. Human muscular fetal cells: a potential cell source for muscular therapies. Pediatr Surg Int 24, 37–47 (2008). https://doi.org/10.1007/s00383-007-2040-5

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00383-007-2040-5

Keywords

Search

Navigation