100
potential of these adult MSCs. Their presence was fi rst reported by the works of
Friedenstein and colleagues in which stromal bone marrow tissue was found to contain
colonies of cells with a spindle-like fi broblastic appearance in vitro (Friedenstein et al.
1968 , 1974 , 1970 ). These cells were found to adhere effectively to plastic in culture,
enabling non-adherent cells that were not MSCs to be fi ltered out. These cells also
showed that after a lag phase of 2–4 days, they have the ability to rapidly proliferate
in vitro, demonstrating their potential to differentiate down mesenchymal lineages into
osteoblasts, adipocytes and chrondrocytes in vitro and following heterotopic transplan-
tation (Friedenstein et al. 1966 ; Friedenstein 1980 ). Further work by others confi rmed
the multipotential nature of mesenchymal stem cells from bone marrow as well as from
many other tissue sites of the human body, such as from skeletal muscle, synovium,
periosteum, adipose tissue and fat pad (Sakaguchi et al. 2005 ; Khan et al. 2012 ).
Adult mesenchymal stem cells are found in very low numbers in most adult tis-
sues, for example, satelli te cells make up only about 5 % of muscle tissue (Alison
et al. 2002 ), and only one out of every 18,000 bone marrow nucleated cells are MSCs
(Muschler et al. 2001 ). These adult MSCs lay quiescent in tissues until activated to
replace local cells that have undergone alterations due to injury, ageing or normal
tissue turnover, restoring natural function to tissues in vivo (Chen and Tuan 2008 ).
Numerous studies have commented on the ability of the use of MSCs in clinical
applications and regenerative medicine due to their ability to adhere to plastic, pro-
liferate and differentiate in vitro, and as they have a low or absent expression of
HLA-2 markers on their cell surface, they are suitable for transplantation, as they
have low immunogenic and high immunosup pressive properties (Le and Ringden
2005 ). One of the best qualities of stem cell therapy is tissue-directed differentiation.
This enables stem cells from one tissue origin to differentiate into another cell type
once transplanted. For example, Concejero and colleagues reported that they were
able to osteogenically differentiate fat-derived stem cells and use them along with
three-dimensional scaffolds to reconstruct rat palatal bone defects (Conejero et al.
2006 ). A phase one clinical trial reported that myocardial regeneration occurred in
patients who had previously had an acute transmural myocardial infarction, as well
as reporting an enhanced left ventricular function and improved tissue perfusion to
infarcted areas after transplantation of bone marrow stem cells (Stamm et al. 2003 ).
Mesenchymal stem cells have demonstrated immense capabilities for their use in
regenerative medicine and clinical applications. One question that poses doubt into
their use is how they are affected by the ageing process. With an increase in the
prevalence of cardiovascular, musculoskeletal and neurological disorders due to an
ageing population, the use of MSCs in autologous transplantation to restore tissues
to their normal function is becoming of greater importance.
5.2 Ageing
The complex progressive process of ageing causes changes in every cell of an
organism, causing a decline in its bodily functions, such as an elongated wound and
bone healing time, los s of lung elasticity and an increased susceptibility to
E. Fossett et al.