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Page 2 of 11 Ghosh et al. Plast Aesthet Res 2024;11:50 https://dx.doi.org/10.20517/2347-9264.2024.70

[3,4]
accessible method of obtaining fat with minimal donor site morbidity . Further work by surgeons such as
Coleman et al. refined both the fat harvest and grafting procedure, with particular emphasis on atraumatic
[5]
harvest and small aliquot grafting to increase the viability of fat .

However, despite the best efforts of improved technology and user experience, consistency in fat grafting
results remains elusive, with resorption rates quoted between 30%-70% within the first year . This may be
[6]
attributed to technical aspects of fat harvest, processing, and injection, as well as the natural heterogeneity of
the cell population within the graft itself . Methods to increase predictability of results, and specifically
[7-9]
volume retention, have therefore been highly sought after. There are several proposed mechanisms for graft
survival. First, adipose grafts, like skin grafts, are dependent on nutrient diffusion from the recipient site
until neovascularization. The host replacement theory states that host histiocytes would eventually take the
place of grafted fat, and the cell survival theory states that a subpopulation of grafted fat is able to survive in
the new host environment . In 2001, Zuk et al. identified adult, multipotent progenitor cells within the
[10]
stroma of the adipose tissue. Subsequent work over the past few decades has deemed the cell survival theory
the predominant mechanism, with adipose-derived stem cells (ASCs) contributing substantially to mature
adipocytes in grafted fat [11,12] . In addition, the paracrine effect of these cells on the graft and surrounding
tissue continues to be uncovered.

The discovery of ASCs opened the door for a variety of adipose-derived therapeutics in regenerative
medicine. Among such applications is the concept of supplementing traditional grafts with progenitor cells
from the stromal vascular fraction (SVF), or so-called “cell-assisted lipotransfer” (CAL). Cell
supplementation has been proposed to improve graft survival or retention, but more recently set the
foundation for engineered adipose grafts in several translational applications.

CELLULAR COMPONENTS OF FAT
Adipose tissue is comprised of numerous cell populations, including adipocytes, ASCs, fibroblasts, immune
cells, and endothelial cells, among others. A 2009 study by Eto et al. examined the components of human fat
tissue, and found that mature adipocytes comprised only a small fraction of aspirated fat, while the majority
of cells were termed “vasculature-associated cells” and included ASCs, inflammatory cells, and endothelial
cells . The isolation of these latter cells from fat was first described by Rodbell et al. in 1966 and has largely
[13]
remained the same conceptually - fat harvesting, processing, collagenase digestion, and resuspension to
acquire the SVF consisting of ASCs, fibroblasts, vascular progenitor cells, pericytes, and endothelial
cells [14,15] . This SVF, when transplanted along with fat grafts, has been shown on a cellular level to actively
participate in adipogenesis and angiogenesis . ASCs can further be expanded from the SVF and are able to
[16]
differentiate into a variety of cell lineages with similar multipotency to bone marrow-derived stem cells [17,18] .
The ASC population is activated under hypoxic conditions that predominate the microenvironment of
grafted fat. The activation of ASCs contributes to both adipocyte repair through differentiation into
adipocytes and integration with surviving grafted fat, as well as angiogenesis via differentiation into
endothelial cells [19-22] . Beyond direct cellular and vascular contributions, the paracrine effects of ASCs and
the SVF increase the production of collagen and elastin, further promoting surrounding adipogenesis and
angiogenesis while reducing fibrosis [23,24] .

FAT AND SVF HARVEST TECHNIQUES
The optimal grafting technique to preserve fat viability and minimize adipocyte death is controversial. The
traditional Coleman technique emphasized fat harvest using an atraumatic process with a 3-mm cannula
attached to a 10-cc syringe, followed by centrifugation and injection of small aliquots of fat into multiple
tissue planes [25-27] . However, further research has found suction-assisted liposuction (SAL) and power-