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322                                                                                  Lin et al.

               Actually, several lines of evidence suggest that
             ADSCs are vascular precursor cells. Many studies
             have shown that SVF contains progenitor cells
             that are able to differentiate into endothelial cells
             and participate in blood vessel formation. Also, a
             recent study demonstrated that SVF cells express-
             ing both pericyte and mesenchymal markers reside
             in a periendothelial location and stabilize endot-
             helial networks [22]. Another recent study showed
             that ADSCs transplanted into ischemic cortex
             preferentially migrate toward microvessels where
             they differentiate into vascular SMCs [2]. By
             extensive histology, flow cytometric assay, it was
             shown that smooth muscle actin (SMA) and CD31
             localized within smooth muscle and endothelial
             cells, respectively, in all blood vessels examined.
             CD34 localized to both the intima (endothelium)  Figure 1 A hypothetical scheme of the adipose-derived
             and adventitia, neither of which expressed SMA.  stem cells niche consists of four components: cap cells-
             The niche marker Wnt5a was confined exclusively  endothelial cells, basal membrane, supporting cells-
             to the vascular wall, within mural SMCs. Surpris-  pericytes, and stem cells.
             ingly, the widely accepted MSC marker STRO-1
             was expressed exclusively in the endothelium of
             capillaries and arterioles but not in the endothe-  metric sorting, these ADSCs have been shown to
             lium of arteries. The ESC marker SSEA1 localized  share many of the same cellular markers with the
             to a pericytic location in capillaries and in certain  BMSCs, such as CD9, CD10, CD13, CD29,
             SMCs of arterioles. Cells expressing the ESC    CD117, CD34, CD90, CD105, and STRO-1
             markers telomerase and OCT4 were rare and       (Table 1).
             observed only in capillaries. Tang et al. also    The ADSCs display multipotency by retaining
             identified the progenitor cells in WAT within    the ability to differentiate into cell types of differ-
             the adipose vasculature [18]. Notably, Rodeheffer  ent lineages, including neurogenic, chondrogenic,
             et al. reported a similar result by employing a  osteogenic, adipogenic, myogenic, cardiomyo-
             variety of approaches [17]. Based on these findings  genic, vascular/endothelial, hepatic, and pan-
             and evidence gathered from the existing literature,  creatic differentiation (Figure 2). In the current
             it has been proposed that ADSCs are vascular pre-  review, we mainly focus on neurogenic differentia-
             cursor (stem) cells at various stages of differentia-  tion, smooth muscle differentiation, and endothe-
             tion [8]. These studies serve to solidify the idea  lial differentiation, which encompass the dominant
             that ADSCs are in fact derived from the adipose  differentiation pathways for functional cells
             vasculature where the stem cells reside in a    located within the penile erectile tissue.
             microenvironment that has been hypothetically
             named as the ADSC niche (Figure 1).             Neuron Differentiation
                                                             It has been shown that ADSCs can be induced by
                                                             isobutylmethylxanthine (IBMX) to differentiate
             The Isolation and Differentiation of ADSCs In Vitro
                                                             into neuron-like cells in vitro [5,10,25]. This
             In recent years, the ADSCs as a new source of   IBMX-induced neuronal differentiation was medi-
             ASCs have been extensively explored [14,23,24].  ated by the IGF-I signaling pathway. The signifi-
             The ADSCs can be developed with a series of steps  cance of these studies is that ADSCs have the
             including isolation, sorting, culture, differentia-  potential to treat degenerative neurological dis-
             tion, and application. Firstly, the adipose tissue was  eases including neurogenic erectile dysfunction
             digested with collagenase type IA, sorted by a cell  (ED), which frequently occurs in patients who
             strainer and specific stem cell markers [4]. These  have undergone pelvic floor surgeries or radiation.
             cells can be cultured in regular culture medium   Due to the fact that future clinical applica-
             and can be induced into different cell types using  tions will likely use these ASCs in an autologous
             induction medium. Afterward, the cells can be   fashion, ADSCs could be induced to differentiate
             used for many different purposes. Using flow cyto-  into neuron-like cells which expressed neuronal

             J Sex Med 2009;6(suppl 3):320–327
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