CARDIOVASCULAR JOURNAL OF AFRICA • Vol 22, No 3, May/June 2011
150
AFRICA
supplied with specialised free fatty acids by the perinodal adipo-
cytes, and dendritic cells from the lymph nodes are able to modu-
late lipolysis of the surrounding adipose tissue.
86
Furthermore,
the adipokine, leptin has been shown to have effects on immune
system functionality. Subjects with a leptin gene mutation have
very low serum leptin levels and reduced numbers of CD
4
+
T
cells and low T-cell proliferation rates. All these defects are
normalised by administration of exogenous leptin.
87
Fat as a source of stem cells
Our perception of adiposity has recently changed again. In addi-
tion to being an energy store, a major protagonist in the develop-
ment of insulin resistance and a modulator of satiety, adipose
tissue has been found to be an abundant store of stem cells.
Adipose tissue may therefore be seen more positively, given that
these cells may be used to treat a multitude of diseases.
Originally, Young
et al
.
88
isolated stem cells by digesting the
connective tissue in fat and cultured the liberated cells, which
they labelled the stromal vascular fraction (SVF). This was
an unpurified population containing stromal cells, endothe-
lial progenitor cells, fibroblasts and haematopoietic stem cells,
89
which were used to produce neo-vascular cells. The multipoten-
tial mesenchymal precursor cells that are harboured within the
SVF may not only be differentiated into adipocytes,
90-92
but also
bone-forming osteoblasts,
90,93,94
muscle myoblasts,
93,95
cardiomyo-
cytes
96
and cartilage-forming chondrocytes.
90,93
Consequently,
there is considerable interest in these adipose-derived stromal
cells (ADSCs)
93,94
for regenerative medicine. This is not only for
the replacement of damaged fat,
97
bone,
98-100
muscle
101
and carti-
lage,
102
for it has been found that ADSCs also secrete cytokines,
such as VEGF, HGF and SDF-19,
103,104
which stimulate angio-
genesis. These cells may therefore be used to treat ischaemic
disease,
105
such as fibrosis and osteoradionecrosis, which are
late complications of radiotherapy.
106
It has also been found
that the growth factors that ADSCs secrete stimulate fibroblast
and keratinocyte growth and therefore ADSCs have been used
to aid skin repair.
107
Unlike bone marrow-derived stromal cells
(BMSCs), a prominent redeeming feature of ADSCs is their ease
of isolation.
108
ADSCs and fat transplantation have been successfully used
after trauma and surgical resection such as mastectomy,
109,110
where ADSCs help to abrogate problems with angiogenesis and
the long-term viability of grafts.
111-113
ADSCs have also been
used to treat lipodystrophy,
114
which has become common due
to side effects of antiretroviral therapies (ART) in HIV-positive
patients.
115,116
These ADSCs are expanded in number
in vitro
and
differentiated into mature adipocytes using a cocktail including
insulin, the cAMP inducer IBMX, a PPAR
g
agonist indometh-
ecin and a low concentration of a glucocorticoid such as dexa-
methasone.
117,118
The use of different cocktails enables ADSCs
to be differentiated into osteoblasts, myocytes or chondrocytes.
Lee
et al
.
119
was the first to demonstrate that ADSCs could be
differentiated into bone-forming osteoblasts and these cells were
used to heal critically sized calvarial defects in mice. In a direct
comparison during this investigation, ADSCs were found to have
the same efficacy as BMSCs. It was established, using genetic
analysis that 96% of the new bone was from the female donor
rather than from the male recipient.
120
As both adults and chil-
dren over the age of two years are unable to correct large cranial
defects due to inadequate ossification, this application has direct
relevance in man and was first used to correct a 120-cm
2
defect
in a seven-year-old girl with a severe head injury.
121
The differentiation of ADSCs into myocytes is relatively
inefficient and gives a low yield and low reproducibility.
89
Glucocorticoids and 5% horse serum are used to supplement
the growth media to stimulate the fusion of cells to form
multi-nucleated myotubes which express myocyte markers.
90,93,122
Although
in vitro
differentiation is far from optimal, these cells
have been used to correct defects in the tibialis anterior muscle in
a mouse model for Duchennes’s muscular dystrophy.
The differentiation of ADSCs into chondrocytes is also
inefficient. Insulin, TGF
β
1 and ascorbic acid
122,123
are used to
stimulate chondogenesis in ADSCs, which takes two weeks, but
unfortunately the yield is far less than when using BMSCs.
123
As cartilage repair
in vivo
is often difficult and slow, the use of
ADSCs to treat traumatised and arthritic joints and to aid joint
reconstruction still warrants further research
102
and promises to
improve therapy for cartilage repair in the future.
Adult mesenchymal stem cells isolated from the adipose
tissue of rabbits are able to differentiate into cardiomyocytes
when treated with 5-azacytidine.
96
This process has also been
observed in human ADSCs cultured in the presence of dimethyl-
sulfoxide.
124
Furthermore, such cells were used to improve
cardiac function and increase survival rate in a rodent model of
myocardial infarction.
124
Similar results were obtained in experi-
ments in which undifferentiated ADSCs were transplanted into
rodent
125,126
and porcine
127
infarcted hearts. These data suggest
that at least in non-human models of myocardial infarction,
ADSCs may be used to repair damaged cardiac tissue, although
their utility in humans is still not known and requires further
investigation.
Fat and the future
The future certainly looks secure for fat. The prevalence of
obesity in the developing world shows no sign of abating,
although recent data from the USA shows evidence of plateau-
ing.
128
The rising levels of obesity in Africa were expected to
result in an increase in the prevalence of obesity-related disor-
ders, which seems to be the case.
71,129
Africa is also the centre
of an HIV/AIDS epidemic and is therefore suffering a double
burden of communicable and non-communicable diseases.
Studies have shown that HIV infection and ART can both lead to
cardiovascular disease
130
and this will further enhance the current
epidemic of obesity-related diseases on the African continent.
Consequently, the use of ART has converted our view of HIV
infection from a certain death sentence to a chronic disease,
and this is leading to the development of health service infra-
structures that can be used for HIV diagnosis, ART roll out and
patient follow up. Such infrastructure could also be utilised for
the diagnosis and monitoring of non-communicable diseases in
both HIV-positive and HIV-negative subjects.
131
There are a number of interesting aspects of obesity in
African populations that deserve continued investigation. The
more diabetogenic than atherogenic nature of adiposity in
African compared to European subjects is not well understood
and unravelling the molecular mechanisms involved in such
ethnic differences may well uncover new aetiological pathways
of obesity-related diseases. The difference in body fat distribu-
tion between population groups is also worthy of further study,
particularly as African subjects have less visceral fat than
