Reduced Reactivation from Dormancy but Maintained Lineage Choice of Human Mesenchymal Stem Cells with Donor Age

被引:70
作者
Dexheimer, Verena [1 ]
Mueller, Sebastian [2 ]
Braatz, Frank [2 ]
Richter, Wiltrud [1 ]
机构
[1] Orthoped Univ Hosp Heidelberg, Res Ctr Expt Orthoped, Heidelberg, Germany
[2] Heidelberg Univ, Dept Orthoped Surg, Heidelberg, Germany
来源
PLOS ONE | 2011年 / 6卷 / 08期
关键词
HUMAN-BONE-MARROW; PROGENITOR CELLS; STROMAL CELLS; DIFFERENTIATION; SENESCENCE; EXPANSION; COLONIES; NUMBER;
D O I
10.1371/journal.pone.0022980
中图分类号
O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];
学科分类号
07 ; 0710 ; 09 ;
摘要
Mesenchymal stem cells (MSC) are promising for cell-based regeneration therapies but up to date it is still controversial whether their function is maintained throughout ageing. Aim of this study was to address whether frequency, activation in vitro, replicative function, and in vitro lineage choice of MSC is maintained throughout ageing to answer the question whether MSC-based regeneration strategies should be restricted to younger individuals. MSC from bone marrow aspirates of 28 donors (5-80 years) were characterized regarding colony-forming unit-fibroblast (CFU-F) numbers, single cell cloning efficiency (SSCE), osteogenic, adipogenic and chondrogenic differentiation capacity in vitro. Alkaline phosphatase (ALP) activity, mineralization, Oil Red O content, proteoglycan-and collagen type II deposition were quantified. While CFU-F frequency was maintained, SSCE and early proliferation rate decreased significantly with advanced donor age. MSC with higher proliferation rate before start of induction showed stronger osteogenic, adipogenic and chondrogenic differentiation. MSC with high osteogenic capacity underwent better chondrogenesis and showed a trend to better adipogenesis. Lineage choice was, however, unaltered with age. Conclusion: Ageing influenced activation from dormancy and replicative function of MSC in a way that it may be more demanding to mobilize MSC to fast cell growth at advanced age. Since fast proliferation came along with high multilineage capacity, the proliferation status of expanded MSC rather than donor age may provide an argument to restrict MSC-based therapies to certain individuals.
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页数:10
相关论文
共 40 条
[21]   Bone tissue-engineered implants using human bone marrow stromal cells: Effect of culture conditions and donor age [J].
Mendes, SC ;
Tibbe, JM ;
Veenhof, M ;
Bakker, K ;
Both, S ;
Platenburg, PP ;
Oner, FC ;
De Bruijn, JD ;
Van Blitterswijk, CA .
TISSUE ENGINEERING, 2002, 8 (06) :911-920
[22]   Mesenchymal and haematopoietic stem cells form a unique bone marrow niche [J].
Mendez-Ferrer, Simon ;
Michurina, Tatyana V. ;
Ferraro, Francesca ;
Mazloom, Amin R. ;
MacArthur, Ben D. ;
Lira, Sergio A. ;
Scadden, David T. ;
Ma'ayan, Avi ;
Enikolopov, Grigori N. ;
Frenette, Paul S. .
NATURE, 2010, 466 (7308) :829-U59
[23]   Reduced chondrogenic and adipogenic activity of mesenchymal stem cells from patients with advanced osteoarthritis [J].
Murphy, JM ;
Dixon, K ;
Beck, S ;
Fabian, D ;
Feldman, A ;
Barry, F .
ARTHRITIS AND RHEUMATISM, 2002, 46 (03) :704-713
[24]   Aspiration to obtain osteoblast progenitor cells from human bone marrow: The influence of aspiration volume [J].
Muschler, GF ;
Boehm, C ;
Easley, K .
JOURNAL OF BONE AND JOINT SURGERY-AMERICAN VOLUME, 1997, 79A (11) :1699-1709
[25]   Age- and gender-related changes in the cellularity of human bone marrow and the prevalence of osteoblastic progenitors [J].
Muschler, GF ;
Nitto, H ;
Boehm, CA ;
Easley, KA .
JOURNAL OF ORTHOPAEDIC RESEARCH, 2001, 19 (01) :117-125
[26]   CULTURE-EXPANDED HUMAN PERIOSTEAL-DERIVED CELLS EXHIBIT OSTEOCHONDRAL POTENTIAL INVIVO [J].
NAKAHARA, H ;
GOLDBERG, VM ;
CAPLAN, AI .
JOURNAL OF ORTHOPAEDIC RESEARCH, 1991, 9 (04) :465-476
[27]  
Oreffo ROC, 1998, SCAND J RHEUMATOL, V27, P415
[28]   Donor sex and age influence the chondrogenic potential of human femoral bone marrow stem cells [J].
Payne, K. A. ;
Didiano, D. M. ;
Chu, C. R. .
OSTEOARTHRITIS AND CARTILAGE, 2010, 18 (05) :705-713
[29]  
Phinney DG, 1999, J CELL BIOCHEM, V75, P424, DOI 10.1002/(SICI)1097-4644(19991201)75:3<424::AID-JCB8>3.3.CO
[30]  
2-#