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Adipose-Derived Stem Cells and Erectile Dysfunction 321

specialized cells. Right now, the sources of ADSCs Table 1 Molecular phenotype of adipose-derived stem
include three types of adipose tissues, including cells (ADSCs)
brown adipose tissue (BAT), white adipose tissue ADSC positive cellular ADSC negative cellular
(WAT), and bone marrow adipose tissue. markers and gene markers and gene
ADSCs are virtually identical to bone marrow CD9 [16] CD11b [16]
stem cells (BMSCs) in differentiation and thera- CD10 [16] CD14 [8,16,19]
peutic potential and are much easier and safer to CD13 [16] CD19 [16]
CD29 [16]
CD31 [8,16,18]
obtain in large quantities. ADSCs therefore appear CD34 [8,16] CD45 [8,16,20]
to be a better choice for future clinical application CD44 [16] CD79a [16]
within the stem cell field [7]. Meanwhile, the CD49 [16] CD80 [16]
CD117 [16]
CD54 [16]
ADSCs have many advantages compared with CD55 [16] CD133 [16]
BMSCs, including the ability to isolate many more CD59 [16] CD144 [16]
stem cells using a minimally invasive surgical CD73 [16] HLA-DR [16]
CD90 [16,21] CD105 [16,21]
procedure for extraction of the adipose tissue. MyD88 [16] PDGFR-b/CD140 [8]
Although the isolation and characterization of CD106 [16] HLA-II [17,19]
CD146 [16] Lin [21]
ADSCs have been well documented, the in situ
CD166 [16] a-SMA [8]
localization of ADSCs in BAT/WAT is poorly HLA-I [19] Wnt5a [8]
understood. By applying an extensive scan of STRO-1 [21] b-cat [8]
Sca1 [21]
the stem cell markers with immunohistology, it
SSEA1 [8]
was shown that CD34+ cells, the well-described OCT3/4 [8]
progenitor/stem cell in adipose tissue, were clearly P75NTR [21]
Telomerase [8]
localized perivascularly [8]. Also, the isolated and
purified ADSCs have successfully differentiated
into neuron-like cells, smooth muscle cells
(SMCs), and endothelium in vitro [9–11]. Characterization and Localization of ADSCs In Situ
In recent years, there has been much interest in the Tissue
surrounding ADSCs, but the ADSC field of Despite the importance of ADSCs and many pub-
research has actually been around for a long time. lications on their characterization, the molecular
In 1964, Rodbell developed the method of isola- characterization of ADSCs is not well established.
tion of the stromal vascular fraction (SVF) from By employing flow cytometry [16], histology [8],
adipose tissue [12]. In 1978, Bjontorp [13] found and other methods [17,18], several candidate
that periadipocytes have the ability for differentia- cellular markers and genes have been screened
tion, which is defined as one of the properties of (Table 1). Meanwhile, the cellular origin of
stem cells. It was not until 2001 that Zuk et al. [4] ADSCs within adipose tissue remains unknown.
first purified and named the ADSCs. Since their Recently, Yamamoto et al. [21] used immunofluo-
official inception, the ADSCs have been exten- rescence (IF) staining of mouse adipose tissue to
sively studied from basic science to clinical identify cells expressing CD90, CD105, Sca-1,
research. In 2004, a German group successfully and/or p75NTR. The results showed widespread
transplanted ADSCs to repair the cranium of a distribution of each of these markers, suggesting
7-year-old girl [14]. In 2005, an experiment for the that they are not specific for ADSCs. In another
treatment of incontinence using the ADSCs was recent study, Zannettino et al. [19] attempted to
also implemented in a rat model [11]. In prelimi- identify ADSCs in human adipose tissue by
nary unpublished data, the ADSCs have also been employing IF staining for cellular markers 1A6.12,
shown to improve erectile function in neurogenic 1B5, STRO-1, CD146, and 3G5. While these
and diabetic animal models [15]. markers were detected in two large blood vessels of
Compared to other kinds of ASCs, such as bone unknown identity, their location in the adipose
marrow-derived mesenchymal stem cells (MSCs), tissue cannot be inferred due to the lack of adipo-
ADSCs possess a clear advantage due to easy and cytes or any other landmarks in the neighborhood
repeatable access to subcutaneous adipose tissue of these two blood vessels. Furthermore, the study
and the simple isolation procedure. Nevertheless, did not examine the small vessels (arterioles,
limitations on the purification of ADSCs and the venules, or capillaries) in adipose tissue, although
lack of knowledge regarding their cellular and the authors did acknowledge that MSCs, such as
molecular biology characterization are the major ADSCs, likely reside in specialized niches within
hindrances associated with the use of ADSCs. the microvascular networks.

J Sex Med 2009;6(suppl 3):320–327