Abstract
BackgroundBone marrow-derived mesenchymal stem cells (BMSCs) are a widely researched adult stem cell population capable of differentiation into various lineages. Because many promising applications of tissue engineering require cell expansion following harvest and involve the treatment of diseases and conditions found in an aging population, the effect of donor age and ex vivo handling must be understood in order to develop clinical techniques and therapeutics based on these cells. Furthermore, there currently exists little understanding as to how these two factors may be influenced by one another.ResultsDifferences in the adipogenic, chondrogenic, and osteogenic differentiation capacity of murine MSCs harvested from donor animals of different age and number of passages of these cells were observed. Cells from younger donors adhered to tissue culture polystyrene better and proliferated in greater number than those from older animals. Chondrogenic and osteogenic potential decreased with age for each group, and adipogenic differentiation decreased only in cells from the oldest donors. Significant decreases in differentiation potentials due to passage were observed as well for osteogenesis of BMSCs from the youngest donors and chondrogenesis of the cells from the oldest donors.ConclusionBoth increasing age and the number of passages have lineage dependent effects on BMSC differentiation potential. Furthermore, there is an obvious interplay between donor age and cell passage that in the future must be accounted for when developing cell-based therapies for clinical use.
Highlights
Bone marrow-derived mesenchymal stem cells (BMSCs) are a widely researched adult stem cell population capable of differentiation into various lineages
Work by Kirkland et al found that advanced age in rats results in decreased levels of mRNA associated with adipogenic differentiation in preadipocytes [19], a change that has since been linked to decreased expression of CCAAT/enhancer binding protein (C/EBP)-α [20], caused by overexpression of C/EBP homologous protein, and increased release of TNFα [21]
There was a 4.9 ± 0.2 fold increase in cell number in cultures of postnatal BMSCs after 8 days compared to cell number after 24 hours, and confluence in these cultures was reached by day 6
Summary
Bone marrow-derived mesenchymal stem cells (BMSCs) are a widely researched adult stem cell population capable of differentiation into various lineages. As hinted by the role of stem cell senescence and dysfunction in natural aging [4,5,6,7], donor or patient age will be a critical factor that must be accounted for in clinical and laboratory evaluations of stem cell based technology. There is currently little consensus and in many cases conflicting reports regarding the effect of donor age and cell processing on adult mesenchymal stem cell (MSC) function. Studies have found an age related decrease in osteoblastic but not adipogenic differentiation in BMSCs from rats [22] and humans [23,24]. Numerous other studies have found significantly decreased differentiation capability with increasing BMSC donor age, for osteogenic [25,26,27], chondrogenic [28], and myogenic [29] differentiation
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