Publication: Defining adipose tissue-derived
stem cells in tissue and in culture
Authors
Lin, Ching-Shwun ; Xin, Zhong-Cheng ; Deng, Chun-Hua ; Ning, Hongxiu ; Lin, Guiting ; Lue, Tom F.
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Publisher
Murcia: F. Hernández
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DOI
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info:eu-repo/semantics/article
Description
Abstract
Adipose tissue-derived stem cells (ADSC)
are routinely isolated from the stromal vascular fraction
(SVF) of homogenized adipose tissue. Similar to other
types of mesenchymal stem cells (MSC), ADSC remain
difficult to define due to the lack of definitive cellular
markers. Still, many types of MSC, including ADSC,
have been shown to reside in a perivascular location, and
increasing evidence shows that both MSC and ADSC
may in fact be vascular stem cells (VSC). Locally, these
cells differentiate into smooth muscle and endothelial
cells that are assembled into newly formed blood vessels
during angiogenesis and neovasculogenesis.
Additionally, MSC or ADSC can also differentiate into
tissue cells such as adipocytes in the adipose tissue.
Systematically, MSC or ADSC are recruited to injury
sites where they participate in the repair/regeneration of
the injured tissue. Due to the vasculature’s dynamic
capacity for growth and multipotential nature for
diversification, VSC in tissue are individually at various
stages and on different paths of differentiation.
Therefore, when isolated and put in culture, these cells
are expected to be heterogeneous in marker expression,
renewal capacity, and differentiation potential. Although
this heterogeneity of VSC does impose difficulties and
cause confusions in basic science studies, its impact on
the development of VSC as a therapeutic cell source has
not been as apparent, as many preclinical and clinical
trials have reported favorable outcomes. With this
understanding, ADSC are generally defined as
CD34+CD31- although loss of CD34 expression in
culture is well documented. In adipose tissue, CD34 is
localized to the intima and adventitia of blood vessels
but not the media where cells expressing alpha-smooth
muscle actin (SMA) exist. By excluding the intima, which contains the CD34+CD31+ endothelial cells, and
the media, which contains the CD34-CD31- smooth
muscle cells, it leaves the adventitia as the only possible
location for the CD34+ ADSC. In the capillary, CD34
and CD140b (a pericyte marker) are mutually
exclusively expressed, thus suggesting that pericytes are
not the CD34+ ADSC. Many other cellular markers for
vascular cells, stem cells, and stem cell niche have also
been investigated as possible ADSC markers.
Particularly the best-known MSC marker STRO-1 has
been found either expressed or not expressed in cultured
ADSC. In the adipose tissue, STRO-1 appears to be
expressed exclusively in the endothelium of certain but
not all blood vessels, and thus not associated with the
CD34+ ADSC. In conclusion, we believe that ADSC
exist as CD34+CD31-CD104b-SMA- cells in the
capillary and in the adventitia of larger vessels. In the
capillary these cells coexist with pericytes and
endothelial cells, both of which are possibly progenies of
ADSC (or more precisely VSC). In the larger vessels,
these ADSC or VSC exist as specialized fibroblasts
(having stem cell properties) in the adventitia.
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