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Orgun et al. Regenerative mechanisms of adipose-derived stem cells

researchers to channel their effort to understand this effects on vascular diseases, angiogenesis, radiation
phenomenon and the discovery of stem cells. After the injury and chronic wounds including diabetic ulcers.
discovery of mesenchymal stem cells (MSCs) in the Interaction of ASCs with cells of the immune system
bone marrow by Becker et al. in the 1960s, a new was also investigated. Articles with detailed information
[1]
discipline called regenerative medicine has emerged. on ASCs’ molecular interactions with other cells were
Many stem cell lines have been discovered since, eligible for inclusion. Duplicate/similar studies and
but information about most of these is limited due studies without information on ASCs’ effects at the
to problems of availability, viability or potential risks. molecular level were excluded.
However, adipose tissue has proved to be an abundant
and easily accessible source of multipotent stem cells. THE IMMUNOPHENOTYPIC PROPERTIES
This cell population, named adipose-derived stem cells OF ASCS
(ASCs) has been demonstrated to be widely available,
viable and safe. The potential of ASCs administration The immunophenotyping and isolation protocols
has gained much interest for the conditions with limited for the ASCs are still not standardized. Without
or pathological repair of tissue damage caused by a universal protocol, comparison of experimental
various insults. data and future advances are difficult. In order to
achieve a consensus for isolating ASCs, International
Since the discovery of ASCs more than 10 years ago, [2] Federation for Adipose Therapeutics and Science and
their intrinsic properties suggesting similarity to other International Society for Cell Therapy have published
known MSCs such as bone marrow MSCs (BM-MSCs) a joint statement about the phenotypic properties of
were demonstrated, and currently ASCs are accepted these cells as well as SVF cells. [8]
to be MSCs. The abundance of these cells in fat tissue
and the relative simplicity of harvesting fat from patients SVF is a substance which consists not only of ASCs
with procedures such as liposuction have made these but also endothelial cells, erythrocytes, fibroblasts,
cells a primary interest for plastic surgeons. There is a lymphocytes, monocyte/macrophages and pericytes.
[9]
tremendous focus on using stromal vascular fraction The substance of cells in SVF is usually named as “SVF
(SVF) or isolated ASCs as a regenerative therapy cells”. These SVF cells are identified as being negative
method for chronic wounds or for the reconstruction for CD235a and sometimes CD31, yet positive for
of tissue defects after oncological tumor resection, as CD34 or CD45. Further passaging depletes most of the
well as to achieve effective fat grafting or as a skin hematopoietic cells and alters the immunophenotype
rejuvenating product in aesthetic surgical practice. of the remaining cell population, which are mostly
There are active clinical trials investigating the effects ASCs. These culture expanded ASCs are positive
of ASC or SVF administration on several pathological for CD34 (could be negative in further expansions),
conditions. [3,4] This clinical activity is predicted to CD44, CD73, CD90 and CD105 like other MSCs and
expand in the future. negative for CD31 and CD45 [Figure 1]. [10,11] ASCs are
different from BM-MSCs since they are positive for
It is becoming more acknowledged that ASCs have a CD36 (GPIIIb) and negative for CD106 (vascular cell
promising therapeutic potential for a broad spectrum of adhesion molecule-1). [12,13]
medical conditions. We have previously reviewed the
literature on the properties of ASCs and their capacity It is also known that ASCs lose CD34 expression over
as a tool of regenerative medicine. [5-7] Recently, a new time with consecutive passaging. [14] Additionally, ASCs
debate on the regenerative effects of these cells has eventually senesce with consecutive passaging due
been introduced. It is still not clear if ASCs show their to the low telomerase activity. [15] This might lead the
main effects directly by differentiating into mature cells researcher to acquire inaccurate results if senescent
(e.g. osteocytes) at the site of implantation, or by their cells of latter passages are used. For the reliability and
paracrine arsenal of many prominent growth factors standardization of the experiments, it is also advised that
to promote regeneration/remodeling and modulate the ASCs’ multilineage (i.e. adipocytes, chondrocytes
inflammation in the tissue. We have performed a and osteoblasts) differentiation potential should be
literature review of basic and clinical science regarding demonstrated, which is now a common practice.
this subject using the PubMed and Cochrane
databases using “ASCs” and “phenotype” or “isolation” ISOLATION OF ASCS
or “angiogenesis” or “wound healing” or “radiation
injury” or “immune regulation”. A total of 118 articles Since the application of ASCs/SVF is becoming
were reviewed regarding ASCs’ immunophenotypical increasingly common, there is focused interest on
properties and methods of isolation, as well as their efficient isolation and preparation of ASCs from
Plastic and Aesthetic Research ¦ Volume 4 ¦ March 22, 2017 33