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Page 4 of 11 Ghosh et al. Plast Aesthet Res 2024;11:50 https://dx.doi.org/10.20517/2347-9264.2024.70

liposuction led to the lowest. They also found significantly higher SVF concentration from the abdomen,
though ASC concentration did not differ between anatomical sites. Therefore, there is still conflicting
evidence regarding the harvest technique and location in regards to optimizing ASC yield and the donor site
should be chosen based on surgeon preference and patient body habitus.

CELL-ASSISTED LIPOTRANSFER
The majority of work on the utility of CAL has focused on increasing fat graft survival. One of the earliest
demonstrations of this was carried out in 2006 by Matsumoto et al., who augmented human fat grafts with
[48]
isolated SVF from the same samples and subsequently transplanted them into immunodeficient mice .
They found a 35% increased survival in CAL-augmented fat grafts, as well as increased microvasculature
and angiogenesis. One of the first studies in patients was conducted by Yoshimura et al. in cosmetic breast
augmentation, who showed a promising retainment of breast volume at 6 to 12 months post-transplantation
with SVF-enriched fat [49,50] . Improved graft retention in the breast with CAL has subsequently been shown
by several groups, including a prospective trial examining the use of SVF-augmented fat grafting to correct
contour defects following breast-conserving therapy (BCT) [51-54] . One of the few randomized controlled trials
in CAL fat grafting in the breast was done by Kolle et al. in 2020, which compared fat grafts alone to fat
grafts augmented with ex vivo expanded ASCs in comparable cohorts of patients . They found increased
[55]
retention with ASC augmentation compared to fat grafting alone (80.2% vs. 45.1%), as well as superior
subjective outcomes when assessed by blinded observers.

Yoshimura et al. have shown that fat retention in facial fat grafting has an improvement with SVF inclusion
and ASC inclusion . In a prospective study, Koh et al. found a resorption of 46.81% with fat grafting alone
[56]
[57]
compared to 20.59% in fat grafting with cultured ASC inclusion in patients with Parry-Romberg disease .
Improved retention with ASC or SVF supplementation in facial fat grafting in patients with hemifacial
atrophy, facial scarring, and in conjunction with facial cosmetic procedures, has subsequently also been
shown by several groups [58-63] . Another comparative study conducted by Gentile et al. compared enriched vs.
non-enriched fat grafting in 100 patients with facial scarring and soft tissue deformity, finding improved
patient satisfaction in patients treated with enriched fat grafts . A summary of clinical studies is included
[64]
in Table 1.

With the role of supplemental cells well-established within CAL, the unique properties of individual
subpopulations of ASCs have been explored in the basic science literature . Using flow cytometry gating to
[65]
remove endothelial and hemopoietic cells from the SVF (CD31-/CD235a-/CD45-), CD34+ cells were
isolated from the subset and defined as ASCs. BMPR1a+ isolates had pro-adipogenic potential [66-69] . Within
this CD34+ group, individual isolates were further identified with varying properties. Notably, CD146+ cells
were found to further augment angiogenesis via increased expression of VEGF, while CD74+ cells exhibited
antifibrogenic properties by decreasing TGF-β1 and subsequent collagen production. Although both in vivo
and in vitro data have been promising, many logistical barriers remain in attempting clinical
implementation of these results, the most salient of which involves multiple hours of laboratory isolation in
addition to flow cytometry sorting to provide enough cells for minimal volumes of cell-assisted lipofilling.

The use of CAL has also been studied in irradiated tissues. Radiation is a common adjunct to cancer
treatment and can result in skin breakdown, wound healing complications, and poor scarring, among other
complications. One of the earliest studies was conducted by Rigotti et al. in 2007, examining 20 patients who
underwent chest wall or breast radiotherapy and had clinically irreversible complications including fibrosis,
[70]
skin ulceration, and skin retraction . Injection of SVF promoted the regeneration of revascularized
radiated tissue, and led to a subjective improvement in symptoms. In 2016, Luan et al. used SVF enrichment