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Page 2 of 10 Evans et al. Plast Aesthet Res 2020;7:28 I http://dx.doi.org/10.20517/2347-9264.2019.53

for researchers to utilize a cell with similar pluripotency but with the lack of embryonic moral concerns
relating to embryonic stem cells [21-30] . However, concerns on genetic modification along with tumorigenic
potential has led to caution for clinical indications [31-56] .

Adult stem cells, although not as robust as embryonic stem cells, carry significant potential in regenerative
medicine and, with their abundance in fat, carry great significance to plastic surgeons [18,19,37,39,54,56] . They are
capable of transforming into a limited number of cellular phenotypes within a given family and there is
some thought that they may induce further local transformation of cells in a microenvironment through
[13]
paracrine influences. In 2001, Zuk et al. reported a source of mesenchymal stem cells in abundance in
one particular tissue - that being fat. During processing with collagenase, they found an abundance of
cells known as the stromal vascular fraction (SVF) that includes red and white blood cells, immune cells,
endothelial cells, and stem cell precursors [56-80] . Their process of isolation and determination of unique
physical identifiers known as clusters of differentiation allowed the identification of a variety of cells that
with multipotent potential. Various processing techniques have been utilized to isolate these cells. Collagen
isolation is perhaps the most efficient but concerns with the FDA on the use of collagen in the clinical
environment and regulations on minimal manipulation have led to the search for alternative options such
as other processing techniques, filtering or drying, washing, or centrifugation.

While SVF may contribute to regeneration by its different components, it may also use a paracrine
signaling as a means for regeneration based on cross-talk between different cell populations [11,12] . Co-
culture of SVF with adipocytes has yielded induced progenitor preadipocyte formations. SVF can also
promote angiogenesis and neovascularization. We believe that this has great opportunities in the clinical
setting for promoting wound healing, particularly in patients with diabetes and other chronic diseases.
Co-implantation of SVF with endothelial progenitor cells and adipose derived stem cells (ADSCs)
[11]
resulted in improved neovascularization potential . With lipotransfer there is often significant volume
loss but combining with SVF has demonstrated enrichment of fat revascularization, probably through
this mechanism of promoting secretion of a diverse array of cytokines. SVF can also be used to create
highly vascularized tissue engineered human dermo-epidermal skin substitutes for burn wounds. Rigotti
postulated a common sequence of events occurring when SVF is transplanted to radiation-damaged tissue
that ultimately results in tissue reperfusion and recovery of some of the damaged skin [50,81-92] .

Many of therapeutic studies have also described an initial decrease in inflammation and immune response
at the site of SVF injection. When applied to certain disease models, it also tends to decrease inflammatory
cytokines and growth factors [92-117] .

SVF also has a regenerative capacity, probably through the release of cytokines. SVF increases proliferation
of fibroblasts when injected in diabetic foot ulcers. There is also some evidence that it might promote nerve
[21]
regeneration . Diabetic foot disease is a multibillion dollar drain to the health care system, thus utilization
of options that could prevent or improve wound healing would be monumental.

Once isolated from adipose tissue, the stromal cell populations represent a diverse collection of cell types.
The key concept however is that they are free of lipid and one can mark the cell types with numerous CD
(cluster of differentiation) markers. Endothelial precursors are distinctive for bearing the CD 31 antigen
and comprise approximately 25%-30% of the mixture of cells. It should be noted however that endothelial
precursors bear more markers than just CD 31. Cells for CD 34 markers are considered early multipotent
progenitor cells and are considered the true “pre-adipocyte”. Further “pericytes” are thought to give rise
to many of the stromal cell populations. Stem cells sense and respond through differentiation to various
mechanical cues, growth factors adhesive ligand density, and other factors. It is not only cell differentiation
but also cell proliferation, angiogenesis, and cell signaling that are affected by these factors. The rest of this
manuscript considers the use of these cells in the clinical setting [11,12] .