BackgroundDegenerative diseases are a major public health concern for the aging population and mesenchymal stem cells (MSCs) have great potential for treating many of these diseases. However, the quantity and quality of MSCs declines with aging, limiting the potential efficacy of autologous MSCs for treating the elderly population.MethodsHuman bone marrow (BM)-derived MSCs from young and elderly donors were obtained and characterized using standard cell surface marker criteria (CD73, CD90, CD105) as recommended by the International Society for Cellular Therapy (ISCT). The elderly MSC population was isolated into four subpopulations based on size and stage-specific embryonic antigen-4 (SSEA-4) expression using fluorescence-activated cell sorting (FACS), and subpopulations were compared to the unfractionated young and elderly MSCs using assays that evaluate MSC proliferation, quality, morphology, intracellular reactive oxygen species, β-galactosidase expression, and adenosine triphosphate (ATP) content.ResultsThe ISCT-recommended cell surface markers failed to detect any differences between young and elderly MSCs. Here, we report that elderly MSCs were larger in size and displayed substantially higher concentrations of intracellular reactive oxygen species and β-galactosidase expression and lower amounts of ATP and SSEA-4 expression. Based on these findings, cell size and SSEA-4 expression were used to separate the elderly MSCs into four subpopulations by FACS. The original populations (young and elderly MSCs), as well as the four subpopulations, were then characterized before and after culture on tissue culture plastic and BM-derived extracellular matrix (BM-ECM). The small SSEA-4-positive subpopulation representing ~ 8% of the original elderly MSC population exhibited a “youthful” phenotype that was similar to that of young MSCs. The biological activity of this elderly subpopulation was inhibited by senescence-associated factors produced by the unfractionated parent population. After these “youthful” cells were isolated and expanded (three passages) on a “young microenvironment” (i.e., BM-ECM produced by BM cells from young donors), the number of cells increased ≈ 17,000-fold to 3 × 109 cells and retained their “youthful” phenotype.ConclusionsThese results suggest that it is feasible to obtain large numbers of high-quality autologous MSCs from the elderly population and establish personal stem cell banks that will allow serial infusions of “rejuvenated” MSCs for treating age-related diseases.Electronic supplementary materialThe online version of this article (doi:10.1186/s13287-017-0688-x) contains supplementary material, which is available to authorized users.

CH 3 ) 2 Pt(µ-SMe 2 )] 2 catalyzes the formation of aryl methyl ethers Via selectiVe C-F bond actiVation of polyfluoroarylimines. This reaction is functional group tolerant and proceeds in good to excellent yields. The optimization and preliminary substrate scope of this process are described.The activation of strong carbon-element bonds remains a significant challenge in organometallic chemistry. In recent years, platinum-based complexes have shown increasing potential for selective carbon-atom bond activation. Detailed mechanistic investigations of these transformations have brought new understanding to the range of reactivity accessible. Significant advances in platinum chemistry include carbon-hydrogen 1 and carbon-halogen bond activation, 2 complexes of heavier element species, 3 reductive elimination from both Pt(II) 4 and Pt(IV) species, 5 dehydrogenation, 6 and a range of applications such as sensors for SO 2 and other gases, 7 biosensors, 8 and photochemical products. 9 Moreover, the use of Pt(II)/Pt(IV) redox cycles in catalysis is becoming increasingly common. In particular, we have been interested in using Pt(II) complexes to catalyze the activation and subsequent functionalization of aryl C-F bonds. Although several examples of stoichiometric 1a,r,2b,10 and catalytic C-F activation have been reported, 11 only limited examples for the catalytic cross-coupling of polyfluoroarenes have emerged. 12 We recently reported that [(CH 3 ) 2 Pt(µ-SMe 2 )] 2 catalyzes the methylation of a wide range of fluorinated aryl Crespo, M.; Granell, J.; Vizcarro, A.; Zafrilla, J.; Font-Bardia, M.; Solans, X. Albrecht, M.; Lutz, M.; Schreurs, A. M. M.; Lutz, E. T. H.; Spek, A. L.; van Koten, G. Dalton Trans. 2000, 3797-3804. (c) Albrecht, M.; Lutz, M.; Spek, A. L.; van Koten, G. Nature (London) 2000, 406, 970-974. (d) Albrecht, M.; Gossage, R. A.; Lutz, M.; Spek, A. L.; van Koten, G.

Mesenchymal stem cells (MSCs) are highly responsive to cues in the microenvironment (niche) that must be recapitulated ex vivo to study their authentic behavior. In this study, we hypothesized that native bone marrow (BM)- and adipose (AD)-derived extracellular matrices (ECM) were unique in their ability to control MSC behavior. To test this, we compared proliferation and differentiation of bone marrow (BM)-derived MSCs when maintained on native decellularized ECM produced by BM versus AD stromal cells (i.e. BM- versus AD-ECM). We found that both ECMs contained similar types of collagens but differed in the relative abundance of each. Type VI collagen was the most abundant (≈60% of the total collagen present), while type I was the next most abundant at ≈30%. These two types of collagen were found in nearly equal proportions in both ECMs. In contrast, type XII collagen was almost exclusively found in AD-ECM, while types IV and V were only found in BM-ECM. Physically and mechanically, BM-ECM was rougher and stiffer, but less adhesive, than AD-ECM. During 14 days in culture, both ECMs supported BM-MSC proliferation better than tissue culture plastic (TCP), although MSC-related surface marker expression remained relatively high on all three culture surfaces. BM-MSCs cultured in osteogenic (OS) differentiation media on BM-ECM displayed a significant increase in calcium deposition in the matrix, indicative of osteogenesis, while BM-MSCs cultured on AD-ECM in the presence of adipogenic (AP) differentiation media showed a significant increase in Oil Red O staining, indicative of adipogenesis. Further, culture on BM-ECM significantly increased BM-MSC-responsiveness to rhBMP-2 (an osteogenic inducer), while culture on AD-ECM enhanced responsiveness to rosiglitazone (an adipogenic inducer). These findings support our hypothesis and indicate that BM- and AD-ECMs retain unique elements, characteristic of their tissue-specific microenvironment (niche), which promote retention of MSC differentiation state (i.e. “stemness”) during expansion and direct cell response to lineage-specific inducers. This study provides a new paradigm for precisely controlling MSC fate to a desired cell lineage for tissue-specific cell-based therapies.