Page 5 - Sexual Health Treatments

324 Lin et al.

pharmacologic agents. From their results, it has has also been successfully demonstrated in animal
been demonstrated that the adipose-derived cells models but has not reached clinical trials [29–31].
have the potential to differentiate into functional On the other hand, recent studies have shifted to
SMCs and thus, adipose tissue can be a useful cell-based therapies, such as using progenitor and
source of cells for treatment of injured tissues stem cells [32–34].
where smooth muscle plays an important role. It has been previously shown that ADSCs were
Furthermore, Lee et al. [27] explored the regu- localized within the vasculature of adipose tissue
lation of SMC marker a-SMA during the dif- [8] and displayed multipotency, as witnessed by the
ferentiation of ADSCs to SMCs. The ADSCs ability of ADSCs to differentiate into endothelial
differentiated toward the SMC lineage under the cells. It has been hypothesized that ADSCs could
exogenous biochemical stimulation. The immun- be used to restore the endothelial function in vas-
ofluorescence staining and Western blot analysis culogenic ED.
detected protein expression of the early SMC
marker a-SMA in both control and experiment
groups. Expression of a-SMA in ADSCs signifi- Mechanism of the Differentiation of ADSCs
cantly increased when treated with transforming A central question in stem cell research is how
growth factor-b1, while a-SMA expression only stem cells maintain the ability to self-renew and
slightly increased in the presence of retinoic replicate while producing differentiated daughter
acid (RA), b-mercaptoethanol, and ascorbic acid. cells, in addition to which signaling events con-
Treatment with platelet-derived growth factor- trol stem cell proliferation and differentiation
BB, RA, and dibutyryl-cyclic adenosine mono- [1,3,7,35,36]. Meanwhile, much research effort has
phosphate decreased the expression of a-SMA been implemented in manipulating stem cells into
significantly. desired cell types for use in clinical application.
More interestingly, in 2008, Andersen et al. [20] Studies have revealed that stem cells use evolution-
found a non-hematopoietic “side population” of arily conserved molecular pathways and machinery
CD45(-) cells within ADSCs possessing the ability for their differentiation and self-renewal. Genes
to differentiate into SMCs. Simultaneous quantita- that participate in these events are regulated at
tive reverse transcriptase polymerase chain reaction different levels, such as transcription, translation,
(qRT-PCR) of 64 genes revealed that the freshly and protein modification.
isolated CD45(-) was highly enriched for cells Recently, it has been demonstrated that transla-
expressing genes related to stem cells, the Notch tional regulation of fibroblast growth factor 2
pathway, and early vascular precursors. Notably, (FGF2) plays a critical role in maintaining self-
the expression of SMA, C-met, and CD34 together renewal and differentiation of ADSCs [37–40]. It
with Angpt2, Flk1, VE-cadherin, and CD31 sug- was also noted that FGF2 is the key molecule for
gested a phenotypic resemblance to pericytes. It has maintenance of stemness in ADSCs [41]. In this
been observed in vitro myogenic specification of regard, FGF2 appears to be of similar importance
CD45(-) cells when cocultured with myoblasts. for hADSCs self-renewal as leukemia inhibitory
Furthermore, immediate intramuscular engraft- factor (LIF) is for mouse ESCs. However, currently
ment of non-cultured CD45(-) cells gave rise to the mechanism is far from well being understood.
myofibers and cells lining blood vessels.

Endothelium Differentiation
Application of Stem Cells/ADSCs
Endothelial dysfunction is a prominent feature of a
wide variety of diseases including ED, and thera- Stem Cell-Based Therapy for ED
peutic angiogenesis is one of the strategies that A cavernous nerve injured rodent animal model
have been considered for the restoration of endo- has been successfully applied in the research
thelial function. It has been reported that ED was for experimental ED [42]. In 2003, Deng et al.
improved by increasing circulating endothelial showed that BMSCs transduced with eNOS were
progenitor cells [28]. Earlier efforts of this thera- able to improve the erectile function of aged rats
peutic strategy largely focused on injection of [43]. In 2004, Bochinski et al. showed that ESC
proangiogenic proteins or vectors expressing such transfected with brain-derived neurotrophic factor
proteins. These efforts were fruitful in preclinical (BDNF) could restore the erectile function of
studies but encountered obstacles in clinical trials. rats whose cavernous nerves were experimentally
Gene transfer and growth factor therapy for ED damaged [34]. Bivalacqua et al. [32,33] showed

J Sex Med 2009;6(suppl 3):320–327