Rescuing replication and osteogenesis of aged mesenchymal stem cells by exposure to a young extracellular matrix.
This study aimed to determine whether aging negatively affects MSC replication and osteogenesis and whether these features could be altered by exposure to an extracellular matrix (ECM) generated by marrow cells from young or old mice. A cell-free ECM was prepared from cultured femoral marrow cells from either 3- or 18-mo-old C57BL/6 mice (young-ECM or old-ECM, respectively). The replication and osteogenesis of young or old MSCs maintained on young-ECM vs. old-ECM as well as plastic were examined in vitro and in vivo. We found that the frequency of MSCs in marrow from old mice, measured by colony-forming cells, was only marginally lower than that of young mice. In contrast, defects in the self-renewal and bone formation capacity of old MSCs were remarkable. These defects were corrected by provision of a young-ECM but not old-ECM. In parallel cultures maintained on a young-ECM, the intracellular levels of reactive oxygen species from both old and young mice were reduced 30-50% compared to those maintained on old-ECM or plastic. We concluded that aging negatively affects the formation of an ECM that normally preserves MSC function, and aged MSCs can be rejuvenated by culture on a young-ECM.
Division of Research, Department of Comprehensive Dentistry, The University of Texas Health Science Center at San Antonio, San Antonio, Texas 78229-3900, USA.
Yun
Y
Sun
Weiping
W
Li
Zhengding
Z
Lu
Richard
R
Chen
Jian
J
Ling
Qitao
Q
Ran
Robert L
RL
Jilka
Xiao-Dong
XD
Chen
D000818:Animals; D018929:Cell Culture Techniques / Q000379:methods*; D002454:Cell Differentiation / Q000502:physiology; D002478:Cells, Cultured; D005109:Extracellular Matrix / Q000378:metabolism*; D005260:Female; D059630:Mesenchymal Stem Cells / Q000166:cytology* / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D010012:Osteogenesis / Q000502:physiology; D017382:Reactive Oxygen Species / Q000378:metabolism
D017382:Reactive Oxygen Species
Tissue Eng. 2007 Feb;13(2):385-91
17518571
Endocrinology. 2005 Apr;146(4):1983-90
15618351
Curr Protoc Cell Biol. 2001 May;Chapter 10:Unit 10.4
18228298
Stem Cells. 2004;22(5):823-31
15342946
J Bone Miner Res. 2007 Dec;22(12):1943-56
17680726
Aging Cell. 2007 Jun;6(3):371-82
17381551
Cell. 2006 Aug 25;126(4):677-89
16923388
Cell. 2005 Feb 25;120(4):437-47
15734677
J Biol Chem. 2004 Dec 31;279(53):55137-46
15496407
Bone. 2006 Sep;39(3):513-22
16616713
Stem Cells. 2006 Apr;24(4):1054-64
16322639
Cell. 2005 Feb 25;120(4):483-95
15734681
Cell Res. 2008 Jul;18(7):725-32
18574498
Nat Biotechnol. 2007 Jul;25(7):803-16
17572666
Blood. 2000 Dec 1;96(12):3763-71
11090058
Science. 2006 Mar 31;311(5769):1880-5
16574858
Mech Dev. 2003 Nov;120(11):1327-36
14623441
Biomaterials. 2000 Jun;21(11):1103-14
10817262
J Biol Chem. 1969 Nov 25;244(22):6049-55
5389100
Cell. 2004 Mar 19;116(6):769-78
15035980
Blood. 2007 Feb 15;109(4):1743-51
17062733
Free Radic Biol Med. 1999 Nov;27(9-10):951-65
10569628
Ageing Res Rev. 2006 Feb;5(1):91-116
16310414
Science. 1999 May 14;284(5417):1168-70
10325227
Transplantation. 1997 Apr 27;63(8):1059-69
9133465
J Clin Invest. 2001 Apr;107(7):803-12
11285299
Cell. 2007 Jan 26;128(2):325-39
17254970
Cell. 2005 Feb 25;120(4):513-22
15734683
Bone. 2004 Jul;35(1):83-95
15207744
Transfusion. 2008 Apr;48(4):620-8
18194385
Free Radic Biol Med. 2003 Feb 15;34(4):496-502
12566075
J Biol Chem. 2005 Aug 26;280(34):30481-9
15964849
Matrix Biol. 1998 Apr;17(1):1-19
9628249
Stem Cells Dev. 2010 Jul;19(7):1095-107
19737070
Science. 1999 Apr 2;284(5411):143-7
10102814
J Biol Chem. 1969 Nov 25;244(22):6056-63
4981789
EMBO J. 1983;2(12):2355-61
6141938