Comparison of growth and differentiation of fetal and adult rhesus monkey mesenchymal stem cells.
The goal of this study was to compare the growth and differentiation potential of fetal and adult rhesus monkey (Macaca mulatta) mesenchymal stem cells (rhMSCs). rhMSCs were obtained from healthy early third-trimester fetal (n = 3) and adult (n = 3) rhesus monkey bone marrow. Fetal rhMSCs were plated at 10, 50, 100, or 1,000 cells/cm(2) in medium containing 10% or 20% infant monkey serum (IMS) or fetal bovine serum (FBS). Fetal rhMSCs grown at 1,000 cells/cm(2) in 20% FBS showed faster growth rates and differentiation toward adipogenic, chondrogenic, and osteogenic lineages when compared to other culture conditions and to adult cells (p < 0.05). Fetal rhMSC showed higher population doubling times (11.3 +/- 0.5) when compared to adult cells (7.3 +/- 0.8) during the first three passages. Adult rhMSC did not grow beyond the third passage under all culture conditions, including those supplemented with insulin-like growth factor (IGF)-I, IGF-II, platelet-derived growth factor (PDGF), and fibroblast growth factor-2 (FGF-2). After the third passage, adult rhMSC cultures were observed with large syncytia and with evidence of apoptosis. Cells obtained from these cultures tested positive for simian foamy virus (SFV) by PCR, RT-PCR, and immunofluorescent assay. Adult rhMSCs cultured with 10 microM tenofovir, an antiviral agent, showed normal growth and differentiation for over 20 population doublings. These findings suggest that: (1) fetal rhMSCs possess greater self-renewal and differentiation potential when compared to adult cells; and (2) SFV can inhibit proliferation of adult rhMSCs in culture, whereas the addition of tenofovir can successfully suppress SFV replication in vitro and result in resumed growth.
Lee
C Chang I
CC
California National Primate Research Center, University of California, Davis, 95616, USA.
Ye
Fang
F
Tarantal
Alice F
AF
D000225:Adenine / Q000031:analogs & derivatives / Q000494:pharmacology; D017667:Adipocytes / Q000166:cytology; D000818:Animals; D001854:Bone Marrow Cells / Q000166:cytology* / Q000187:drug effects / Q000821:virology; D002454:Cell Differentiation / Q000187:drug effects / Q000502:physiology*; D049109:Cell Proliferation / Q000187:drug effects*; D002478:Cells, Cultured; D019902:Chondrocytes / Q000166:cytology; D003470:Culture Media / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D005333:Fetus / Q000166:cytology; D016222:Fibroblast Growth Factor 2 / Q000494:pharmacology; D007334:Insulin-Like Growth Factor I / Q000494:pharmacology; D007335:Insulin-Like Growth Factor II / Q000494:pharmacology; D008253:Macaca mulatta; D059630:Mesenchymal Stem Cells / Q000166:cytology* / Q000187:drug effects / Q000821:virology; D063065:Organophosphonates / Q000494:pharmacology; D010006:Osteoblasts / Q000166:cytology; D010982:Platelet-Derived Growth Factor / Q000494:pharmacology; D018894:Reverse Transcriptase Inhibitors / Q000494:pharmacology; D016092:Spumavirus / Q000235:genetics / Q000302:isolation & purification; D000068698:Tenofovir; D013997:Time Factors
D003470:Culture Media; D063065:Organophosphonates; D010982:Platelet-Derived Growth Factor; D018894:Reverse Transcriptase Inhibitors; D016222:Fibroblast Growth Factor 2; D007334:Insulin-Like Growth Factor I; D007335:Insulin-Like Growth Factor II; D000068698:Tenofovir; D000225:Adenine