Human multipotent mesenchymal stromal cells from distinct sources show different in vivo potential to differentiate into muscle cells when injected in dystrophic mice.
Limb-girdle muscular dystrophies are a heterogeneous group of disorders characterized by progressive degeneration of skeletal muscle caused by the absence or deficiency of muscle proteins. The murine model of Limb-Girdle Muscular Dystrophy 2B, the SJL mice, carries a deletion in the dysferlin gene. Functionally, this mouse model shows discrete muscle weakness, starting at the age of 4-6 weeks. The possibility to restore the expression of the defective protein and improve muscular performance by cell therapy is a promising approach for the future treatment of progressive muscular dystrophies (PMD). We and others have recently shown that human adipose multipotent mesenchymal stromal cells (hASCs) can differentiate into skeletal muscle when in contact with dystrophic muscle cells in vitro and in vivo. Umbilical cord tissue and adipose tissue are known rich sources of multipotent mesenchymal stromal cells (MSCs), widely used for cell-based therapy studies. The main objective of the present study is to evaluate if MSCs from these two different sources have the same potential to reach and differentiate in muscle cells in vivo or if this capability is influenced by the niche from where they were obtained. In order to address this question we injected human derived umbilical cord tissue MSCs (hUCT MSCs) into the caudal vein of SJL mice with the same protocol previously used for hASCs; we evaluated the ability of these cells to engraft into recipient dystrophic muscle after systemic delivery, to express human muscle proteins in the dystrophic host and their effect in functional performance. These results are of great interest for future therapeutic application.
Vieira
N M
NM
Human Genome Research Center, Institute of Biosciences, University of São Paulo, Rua do Matão, n.106-Cidade Universitária, São Paulo, SP, CEP: 05508-090, Brazil.
Zucconi
E
E
Bueno
C R
CR
Secco
M
M
Suzuki
M F
MF
Bartolini
P
P
Vainzof
M
M
Zatz
M
M
D050156:Adipogenesis / Q000502:physiology; D000818:Animals; D015153:Blotting, Western; D002454:Cell Differentiation / Q000502:physiology*; D002478:Cells, Cultured; D020219:Chondrogenesis / Q000502:physiology; D006801:Humans; D016130:Immunophenotyping; D051379:Mice; D039902:Multipotent Stem Cells / Q000166:cytology*; D009136:Muscular Dystrophies / Q000628:therapy*; D010012:Osteogenesis / Q000502:physiology; D017154:Stromal Cells / Q000166:cytology*; D014183:Transplantation, Heterologous
Stem Cells. 2008 Jan;26(1):146-50
17932423
J Transl Med. 2009 Jun 18;7:46
19538712
Stem Cells Dev. 2010 Mar;19(3):395-402
19290805
Virchows Arch Pathol Anat Physiol Klin Med. 1963 Aug 8;336:564-9
14136150
Nat Cell Biol. 2010 Feb;12(2):143-52
20081842
Stem Cell Rev Rep. 2009 Dec;5(4):387-401
20058202
Neuromuscul Disord. 2008 Jan;18(1):17-8
18155523
Nat Rev Immunol. 2008 Sep;8(9):726-36
19172693
J Cereb Blood Flow Metab. 1998 Oct;18(10):1099-106
9778186
J Dent Res. 2002 Aug;81(8):531-5
12147742
Nat Cell Biol. 2010 Feb;12(2):153-63
20081841
J Clin Invest. 2007 Oct;117(10):2903-12
17853947
Clin Immunol. 2001 Feb;98(2):235-43
11161980
Stem Cells. 2008 Sep;26(9):2391-8
18583542
Nature. 2006 Nov 30;444(7119):574-9
17108972
Stem Cells. 2004;22(6):981-93
15536189
J Cell Sci. 2000 Jun;113 ( Pt 12):2299-308
10825301
Tissue Eng. 2001 Apr;7(2):211-28
11304456
J Transl Med. 2009 Jan 14;7:6
19144182
Cell. 2006 Dec 29;127(7):1304-6
17190595
Am J Hum Genet. 1995 Mar;56(3):725-31
7887428
Lancet. 2008 May 10;371(9624):1579-86
18468541
Exp Hematol. 2002 Jan;30(1):42-8
11823036
Stem Cells. 2005 Jun-Jul;23(6):828-33
15917478
Nature. 1989 Jan 12;337(6203):176-9
2643055
Proc Natl Acad Sci U S A. 2000 Dec 5;97(25):13625-30
11087820
Biol Cell. 2008 Apr;100(4):231-41
17997718
Stem Cells. 2007 Apr;25(4):875-84
17185606
Neuromuscul Disord. 2002 Feb;12(2):167-73
11738359
Blood. 2004 Mar 1;103(5):1669-75
14576065
Neurobiol Dis. 1996 Apr;3(2):137-47
9173921
J Biomed Sci. 2005;12(1):47-57
15864738
Stem Cells. 2004;22(4):617-24
15277707
Nat Genet. 1999 Oct;23(2):141-2
10508505
Nature. 2010 Sep 16;467(7313):285-90
20644535
J Neurosci. 2004 Feb 25;24(8):1987-95
14985441
Nature. 1999 Sep 23;401(6751):390-4
10517639
Scand J Immunol. 2003 Jan;57(1):11-20
12542793