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groups were also statistically indifferent. In another similar study, by Dexheimer
and colleagues (Dexheimer et al. 2011 ), MSCs were isolated from iliac crest bone
marrow aspirates and comparisons were made of culture outcomes of MSCs from
donors ranging from 5 to 80 years of age. No signifi cant correlation was found
between age and number of colony-forming unit-fi broblasts (CFU-F). It is, how-
ever, suggested that the number of stem cells that can be aspirated per millilitre are
hugely variable (Muschler et al. 1997 ), and therefore, CFU-F data may not be a
reliable outcome variable in these studies. In addition, there are known stages in
bone marrow stem cells numbers: there is continual bone growth until the age of 18
years (Whiting et al. 2004 ) then there is steady decline until the age of 40 years
(D’Ippolito et al. 1999 ), followed by a plateau.
There are authors who have found diffi culties in isolating and/or expanding stem
cells from older aged donors. Bertram et al. ( 2005 ) cultured MSCs isolated from
iliac crest of 21 donors (aged 11–76 years) and from 32 donors of cancellous bone
grafting material (aged 18–34 years). The failure rate for culture was 55.6 % in
donors over 60 years of age, whereas it was up to 22.2 % in donors under 60 years
of age. Age, however, had no signifi cant infl uence on specifi cally isolating MSCs
amongst the different age groups. Shamsul et al. ( 2004 ) isolated MSC from the bone
marrow of 38 donors aged 10–70 years. Fourteen of the 15 samples from donors
over 40 years failed to proliferate. whereas only seven of the 23 samples from the
younger donors failed. It is possible that these were anomalies as culturing of stem
cells from older donors is generally possible by the vast majority of authors.
Where culturing is largely successful , it is observed that during each expansion of
MSC populations, there is increased population doubling (PD) time as donor age
increases. Passage 3 in one study (Dexheimer et al. 2011 ) had a positive correlation
between age and PD time of R 2 = 0.669 ( p < 0.001). Stenderup et al. ( 2003 ) compared
rates of PD between two groups of population ages. Again, using MSCs from bone mar-
row, the mean PD rate was 0.05/day compared to cells from younger donors at 0.09/day.
Others have also examined proliferation rate and have observed a slower rate with cells
from older donors (Mendes et al. 2002 ; Stolzing et al. 2008 ; Chen et al. 2011 ).
Another property to look at is the differentiation potential. Commonly, osteo-
genic potential has been investigated as mineralisation or AP+ cultures can be mea-
sured. De Girolamo and colleagues (de Girolamo et al. 2009 ) isolated adipose-derived
MSCs from two groups of donors: those younger than 35 years and those older than
45 years. They found that the osteoblastic differentiation potential from older donors
was signifi cantly reduced, whereas there was little difference on adipogenic differ-
entiation. Chen et al. ( 2011 ) extracted adipose-derived stem cells (ADSC) and
MSCs from each of their patients of two groups: young (mean 36 years) and elderly
with osteoporotic fractures (mean 71 years). Apart from ADSC displaying no
changes in PD time with age, osteogenic differentiation measured from matrix min-
eralisation also displayed no signifi cant difference between the two groups.
However, BMSC from the elderly group showed much less mineralisation com-
pared to the young donors. Others have also found that there is a loss of osteogenic
potential with increased age (Roura et al. 2006 ).
H.D. Tailor et al.