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Ghosh et al. Plast Aesthet Res 2024;11:50 https://dx.doi.org/10.20517/2347-9264.2024.70 Page 7 of 11

[89]
significant impact on cancer recurrence . Another study conducted by Mazur et al. compared 3-year
recurrence in 56 patients undergoing ASC-supplemented fat grafting with 252 matched patients who did
[90]
not undergo breast reconstruction and found no difference between the two groups . A recent systematic
review by Al Qurashi et al. found an oncologic recurrence incidence of 29/583 in non-irradiated
mastectomy patients and 41/517 in breast conservation patients, suggesting overall safety of fat grafting after
[91]
oncologic surgery . As the use of ASCs and CAL broadens, more refined data are likely to emerge.
Beyond questions of oncologic safety, there has also been codification by the United States Food and Drug
Administration (FDA) acknowledging the use of adipose-derived stem cell isolation and supplementation as
beyond “minimally manipulated” and therefore requiring specific pre-market approval, based on a ruling by
the Southern District of Florida in 2019 [57,92,93] . The report cites the processing of structural tissue and its
transformation into a product that “alter(s) the original relevant characteristics of the tissue relating to the
tissue’s utility for reconstruction, repair, or replacement” as beyond the scope of surgical reconstruction.
The only currently FDA-approved use of stem cells relates to hematopoietic progenitor cells, thus making
regular clinical use of CAL a legal boundary for most providers. The European Medicines Agency has come
[94]
up with similar guidelines and restrictions for the use of ADSCs in the European Union .

FUTURE DIRECTIONS
As clinical use of CAL continues to increase, more rigorous, large cohort studies are needed to both validate
safety and ensure no increased risk of tumorigenesis. Further studies will need to answer questions
regarding the optimal timing of CAL in relation to adjuvant chemotherapy or radiation, as well as ascertain
the expected volumetric clinical survival in these patients. The ratio of stromal vascular fraction to fat in the
clinical setting needs to be further elucidated, as well as if there is a dose-dependent response as seen in
laboratory models. Additionally, isolation of ADC sub-populations and their implementation may be a
potential tool to optimize this technique, although significant logistical barriers remain prevalent. Just as
there has been the development of multiple systems or devices to streamline standard fat grafting, we
anticipate an increase in products to streamline the isolation of progenitor cells from lipoaspirate so as to
keep the cell supplementation within the same surgical procedure and obviate the need for additional
manipulation, culture-expansion, or procedures for CAL.

CONCLUSION
Adipose-derived therapies, such as CAL and engineered tissues, are a burgeoning field that shows promise
in both cosmetic and reconstructive practice. To date, there have been several, mostly retrospective, studies
regarding fat harvest, SVF isolation, and indications for the use of CAL. However, large cohort prospective
trials remain to be done. In addition to currently known uses, the concept of cryopreserved SVF has been an
area of increased study in mouse models [95-97] in an attempt to alleviate the logistical burdens SVF isolation
requires, which in turn may also provide an avenue for ASC subpopulation use in the future. With future
studies and further refinements in technique, engineered adipose therapeutics have the potential to increase
the consistency of survival of grafted fat and thus become a standard approach in the reconstructive
armamentarium.

DECLARATIONS
Authors’ contributions
Made substantial contributions to the conception and writing of the review: Ghosh K, Patel RA, Hanson SE