Abstract
Skeletal muscle-derived myoblasts were initially considered to be a potential source for cardiomyoplasty. These cells were expected to be able to trans-differentiate into cardiomyocytes after transplantation in the cardiac muscle environment. However, several studies have shown differentiation into multinucleated myotubes, and no differentiation into cardiomyocytes has been observed. Complete differentiation of murine skeletal muscle interstitium-derived multipotent stem cells (SKMI-DMSCs) into cardiomyocytes was recently demonstrated following engraftment into the infarcted heart muscle (left ventricle). Engrafted SKMI-DMSCs showed typical formation of gap-junctions, as well as intercalated discs and desmosomes, between donor and recipient and/or donor and donor cells in vivo. When SKMI-DMSCs were co-cultured with embryonic cardiomyocytes on a glass slide, cells typically formed sphere-like cell aggregations together in vitro. These mixed cell aggregations showed spontaneous synchronous contractions with the formation of gap-junctions between aggregated cells. Cardiomyocyte differentiation was also confirmed by the expression of cardiomyogenic transcription factors, such as GATA-4, Nkx2-5, Isl-1, Mef2 and Hand2. Vigorous expression of these factors in the SKMI-DMSCs was seen after co-culture, and lower expression of these factors was also observed in their clonal cell culture. These results indicate that SKMI-DMSCs are a potential source for practical cellular cardiomyoplasty, and that they should be isolated and transplanted in a more primitive state for milieu-dependent differentiation of stem cells.
This is a preview of subscription content, log in via an institution.
Buying options
Tax calculation will be finalised at checkout
Purchases are for personal use only
Learn about institutional subscriptionsReferences
Beauchamp JR, Heslop L, Yu DS, Tajbakhsh S, Kelly RG, Wernig A, Buckingham ME, Partridge TA, Zammit PS (2000) Expression of CD34 and Myf5 defines the majority of quiescent adult skeletal muscle satellite cells. J Cell Biol 151:1221–1234
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 122:289–301
Drowley L, Okada M, Payne TR, Botta GP, Oshima H, Keller BB, Tobita K, Huard J (2009) Sex of muscle stem cells does not influence potency for cardiac cell therapy. Cell Transplant 18:1137–1146
Fouts K, Fernandes B, Mal N, Liu J, Laurita KR (2006) Electrophysiological consequence of skeletal myoblast transplantation in normal and infarcted canine myocardium. Heart Rhythm 3:452–461
Ghostine S, Carrion C, Souza LC, Richard P, Bruneval P, Vilquin JT, Pouzet B, Schwartz K, Menasche P, Hagege AA (2002) Long-term efficacy of myoblast transplantation on regional structure and function after myocardial infarction. Circulation 106:I131–I136
Hagege AA, Carrion C, Menasche P, Vilquin JT, Duboc D, Marolleau JP, Desnos M, Bruneval P (2003) Viability and differentiation of autologous skeletal myoblast grafts in ischaemic cardiomyopathy. Lancet 361:491–492
Horackova M, Arora R, Chen R, Armour JA, Cattini PA, Livingston R, Byczko Z (2004) Cell transplantation for treatment of acute myocardial infarction: unique capacity for repair by skeletal muscle satellite cells. Am J Physiol Heart Circ Physiol 287:H1599–H1608
Hutcheson KA, Atkins BZ, Hueman MT, Hopkins MB, Glower DD, Taylor DA (2000) Comparison of benefits on myocardial performance of cellular cardiomyoplasty with skeletal myoblasts and fibroblasts. Cell Transplant 9:359–368
Joggerst SJ, Hatzopoulos AK (2009) Stem cell therapy for cardiac repair: benefits and barriers. Expert Rev Mol Med 11:e20
LaBarge MA, Blau HM (2002) Biological progression from adult bone marrow to mononucleate muscle stem cell to multinucleate muscle fiber in response to injury. Cell 111:589–601
Laflamme MA, Chen KY, Naumova AV, Muskheli V, Fugate JA, Dupras SK, Reinecke H, Xu C, Hassanipour M, Police S, O’Sullivan C, Collins L, Chen Y, Minami E, Gill EA, Ueno S, Yuan C, Gold J, Murry CE (2007) Cardiomyocytes derived from human embryonic stem cells in pro-survival factors enhance function of infarcted rat hearts. Nat Biotechnol 25:1015–1024
Leobon B, Garcin I, Menasche P, Vilquin JT, Audinat E, Charpak S (2003) Myoblasts transplanted into rat infarcted myocardium are functionally isolated from their host. Proc Natl Acad Sci USA 100:7808–7811
Menasche P (2007) Skeletal myoblasts as a therapeutic agent. Prog Cardiovasc Dis 50:7–17
Min JY, Yang Y, Converso KL, Liu L, Huang Q, Morgan JP, Xiao YF (2002) Transplantation of embryonic stem cells improves cardiac function in postinfarcted rats. J Appl Physiol 92:288–296
Murry CE, Keller G (2008) Differentiation of embryonic stem cells to clinically relevant populations: lessons from embryonic development. Cell 132:661–680
Odorico JS, Kaufman DS, Thomson JA (2001) Multilineage differentiation from human embryonic stem cell lines. Stem Cells 19:193–204
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
Pagani FD, DerSimonian H, Zawadzka A, Wetzel K, Edge AS, Jacoby DB, Dinsmore JH, Wright S, Aretz TH, Eisen HJ, Aaronson KD (2003) Autologous skeletal myoblasts transplanted to ischemia-damaged myocardium in humans. Histological analysis of cell survival and differentiation. J Am Coll Cardiol 41:879–888
Pouzet B, Vilquin JT, Hagege AA, Scorsin M, Messas E, Fiszman M, Schwartz K, Menasche P (2000) Intramyocardial transplantation of autologous myoblasts: can tissue processing be optimized? Circulation 102:III210–III215
Reinecke H, Zhang M, Bartosek T, Murry CE (1999) Survival, integration, and differentiation of cardiomyocyte grafts: a study in normal and injured rat hearts. Circulation 100:193–202
Reinecke H, Poppa V, Murry CE (2002) Skeletal muscle stem cells do not transdifferentiate into cardiomyocytes after cardiac grafting. J Mol Cell Cardiol 34:241–249
Seale P, Sabourin LA, Girgis-Gabardo A, Mansouri A, Gruss P, Rudnicki MA (2000) Pax7 is required for the specification of myogenic satellite cells. Cell 102:777–786
Takahashi K, Tanabe K, Ohnuki M, Narita M, Ichisaka T, Tomoda K, Yamanaka S (2007) Induction of pluripotent stem cells from adult human fibroblasts by defined factors. Cell 131:861–872
Tamaki T, Akatsuka A, Ando K, Nakamura Y, Matsuzawa H, Hotta T, Roy RR, Edgerton VR (2002) Identification of myogenic-endothelial progenitor cells in the interstitial spaces of skeletal muscle. J Cell Biol 157:571–577
Tamaki T, Akatsuka A, Okada Y, Matsuzaki Y, Okano H, Kimura M (2003) Growth and differentiation potential of main- and side-population cells derived from murine skeletal muscle. Exp Cell Res 291:83–90
Tamaki T, Uchiyama Y, Okada Y, Ishikawa T, Sato M, Akatsuka A, Asahara T (2005) Functional recovery of damaged skeletal muscle through synchronized vasculogenesis, myogenesis, and neurogenesis by muscle-derived stem cells. Circulation 112:2857–2866
Tamaki T, Okada Y, Uchiyama Y, Tono K, Masuda M, Wada M, Hoshi A, Akatsuka A (2007a) Synchronized reconstitution of muscle fibers, peripheral nerves and blood vessels by murine skeletal muscle-derived CD34(-)/45 (-) cells. Histochem Cell Biol 128:349–360
Tamaki T, Okada Y, Uchiyama Y, Tono K, Masuda M, Wada M, Hoshi A, Ishikawa T, Akatsuka A (2007b) Clonal multipotency of skeletal muscle-derived stem cells between mesodermal and ectodermal lineage. Stem Cells 25:2283–2290
Tamaki T, Akatsuka A, Okada Y, Uchiyama Y, Tono K, Wada M, Hoshi A, Iwaguro H, Iwasaki H, Oyamada A, Asahara T (2008a) Cardiomyocyte formation by skeletal muscle-derived multi-myogenic stem cells after transplantation into infarcted myocardium. PLoS One 3:e1789
Tamaki T, Okada Y, Uchiyama Y, Tono K, Masuda M, Nitta M, Hoshi A, Akatsuka A (2008b) Skeletal muscle-derived CD34+/45- and CD34-/45- stem cells are situated hierarchically upstream of Pax7+ cells. Stem Cells Dev 17:653–667
Tamaki T, Uchiyama Y, Okada Y, Tono K, Masuda M, Nitta M, Hoshi A, Akatsuka A (2010) Clonal differentiation of skeletal muscle-derived CD34(-)/45(-) stem cells into cardiomyocytes in vivo. Stem Cells Dev 19:503–512
Tamaki T, Tono K, Uchiyama Y, Okada Y, Masuda M, Soeda S, Nitta M, Akatsuka A (2011) Origin and hierarchy of basal lamina-forming and -non-forming myogenic cells in mouse skeletal muscle in relation to adhesive capacity and Pax7 expression in vitro. Cell Tissue Res 344:147–168
Taylor DA, Atkins BZ, Hungspreugs P, Jones TR, Reedy MC, Hutcheson KA, Glower DD, Kraus WE (1998) Regenerating functional myocardium: improved performance after skeletal myoblast transplantation. Nat Med 4:929–933
van Laake LW, Passier R, Monshouwer-Kloots J, Verkleij AJ, Lips DJ, Freund C, den Ouden K, Ward-van Oostwaard D, Korving J, Tertoolen LG, van Echteld CJ, Doevendans PA, Mummery CL (2007) Human embryonic stem cell-derived cardiomyocytes survive and mature in the mouse heart and transiently improve function after myocardial infarction. Stem Cell Res 1:9–24
Winitsky SO, Gopal TV, Hassanzadeh S, Takahashi H, Gryder D, Rogawski MA, Takeda K, Yu ZX, Xu YH, Epstein ND (2005) Adult murine skeletal muscle contains cells that can differentiate into beating cardiomyocytes in vitro. PLoS Biol 3:e87
Author information
Authors and Affiliations
Corresponding author
Editor information
Editors and Affiliations
Rights and permissions
Copyright information
© 2012 Springer Science+Business Media B.V.
About this chapter
Cite this chapter
Tamaki, T. (2012). Skeletal Muscle-Derived Stem Cells: Role in Cellular Cardiomyoplasty. In: Hayat, M. (eds) Stem Cells and Cancer Stem Cells, Volume 2. Stem Cells and Cancer Stem Cells, vol 2. Springer, Dordrecht. https://doi.org/10.1007/978-94-007-2016-9_35
Download citation
DOI: https://doi.org/10.1007/978-94-007-2016-9_35
Published:
Publisher Name: Springer, Dordrecht
Print ISBN: 978-94-007-2015-2
Online ISBN: 978-94-007-2016-9
eBook Packages: Biomedical and Life SciencesBiomedical and Life Sciences (R0)