101infections (Ho et al. 2005 ). Ageing is also seen as a refl ection of the cumulative
senescence of an organism’s component cells (Clark 1999 ). During senescence, the
replicative potential of stem cells halts, and the repairing and replacing process of
damaged cells is prevented, interfering with the function of the tissue involved.
Some studies have suggested that a decline in stem cell numbers throughout the
body may contribute to ageing and the appearance of age-related diseas e such as
osteoarthritis (Ho et al. 2005 ). Previous studies state that on average cells stop
dividing after an average of 50 cumulative population doublings and can remain
alive, unlike apoptotic cells, despite a derangement of function (Fossett and Khan
2012 ; Itahana et al. 2001 ).
Studies investigating the effect of ageing on MSCs have reported inconsistent
results, with some studies fi nding age-related changes and many fi nding no differ-
ence. How ageing affects proliferation rate, differentiation potential and cell surface
characterisation will be discussed here.
5.3 Ageing and Proliferation
It is important to researc h how age affects proliferation rate of MSCs to enable a
decision to be made as to whether MSCs from older patients are suitable for expan-
sion in vitro prior to autologous transplantation, as the need for a biological repair
of age-related diseases is increasing with the ageing population. A mixed result
from studies about the effect of age on proliferation rate has been published by
numerous authors, using various MSC sources, although as with most MSCs stud-
ies, many results have been obtained using bone marrow-derived mesenchymal
stem cell (BMSCs).
A study using BMSCs from three age groups (0–20, 21–40 and >40 years old) by
Stolzing et al. ( 2008 ) looked at the effect of age on proliferation potential. They
found that for the fi rst 5 weeks in culture, growth patterns of all three groups were
similar; however, after 5 weeks, growth of the MSCs from the group older than
40-year-olds began to decline, with the growth curve reaching a plateau compared
to the other two groups. This was investigated for 4 months in culture wi th groups
achieving 17–35 cumulative population doublings. It was also noted that signifi -
cantly lower CFU-f numbers following MNC isolation was seen in the older donors
compared to younger. This was confi rmed using multi-parameter fl ow cytometry
where the frequency of CD45lowD7-FIB + LNGFR+ cells was also found to show
an age-related decline. Shamsul and colle agues also reported a declined prolifera-
tive ability of BMSCs, as 14 out of 15 samples from donors over 40 years old failed
to proliferate compared to 16 out of 23 samples successfully proliferating from
donors younger than 40 years old (Shamsul et al. 2004 ). A more recent study stated
that the time taken for single-seeded BMSCs in 96-well plates to undergo one popu-
lation doubling in passage 3 was more than double for MSCs from older patients
than that of the younger patients (young 37.9 and old 89.4 h per population dou-
blings), providing results that are similar to previous literature (Dexheimer et al.
2011 ). An age-related increase in hours per population doubling was consistently
5 The Effects of Ageing on Proliferation Potential, Differentiation Potential...