Fat Grafting Supplemented by Adipose-Derived Stem Cells for Breast Augmentation



Fig. 36.1
Historical trends in fat grafting. (a) Schematic of traditional fat grafting. Bolus injection results in central necrosis due to lack of blood supply and subsequent oil cyst formation and subcutaneous indurations. (b) Schematic of “Coleman technique.” Multiple injection with small volume of the fat results in receiving more blood supply from the surrounding tissue and subsequent less resorption. (c) Schematic of the so-called cell-assisted lipotransfer (CAL). Fat grafting by Coleman technique together with adipose-derived stem cells obtained from another adipose tissue is considered to be more stable for graft efficacy in terms of angiogenesis and adipogenesis



CAL has been widely used, particularly in the field of aesthetic surgery and reconstructive surgery [34, 35]. The theoretical key benefits of CAL include the direct differentiation of ASCs into adipocytes as a reservoir for adipose tissue turnover; the direct differentiation of ASCs into endothelial cells and the subsequent increase in blood supply to the grafted fat tissue, thereby decreasing the rate of graft resorption; the release of angiogenic growth factors by ASCs and the induction of angiogenesis; protection of the graft from ischemic reperfusion injury by ASCs; and the acceleration of wound healing at the recipient site. ASCs secrete potent growth factors such as vascular endothelial growth factor (VEGF), hepatocyte growth factor (HGF), basic fibroblast growth factor (bFGF), and insulin-like growth factor 1 (IGF-1) [36, 37]. The secretion of VEGF, HGF, or both by ASCs can be induced by the exposure of the cells to hypoxia [37], differentiation factor [38], or tumor necrosis factor α [39]. ASCs have also been shown to enhance tissue survival [40] and protect tissue from ischemia-reperfusion injury [41].

Early studies have demonstrated that CAL may be superior to standard fat grafting in terms of volume retention, with fewer lipofilling sessions required in partial breast reconstruction and the correction of either congenital or acquired facial tissue defect [34, 42]; however, there is no comparison study between CAL and standard fat grafting for breast augmentation. It should also be noted that despite the potential benefits of combined therapy, many aspects of the mechanism of injected fat survival, the way to control the differentiation of ASCs, and the fate of ASCs remain unknown.



36.4 Unresolved Issues in the Application of Fat Grafting with ASCs to the Breasts


Although there has been no comparison study between CAL and standard fat grafting for cosmetic breast augmentation, murine studies have demonstrated that CAL may be superior compared with fat grafting alone, with CAL producing a lower graft absorption rate, higher capillary density, lower tissue cyst formation, and less necrosis [9, 43]. However, the concentration of stem cells in the murine grafts was supraphysiological, with concentrations of 6,250 and 1,250 times physiological levels, respectively [44]. By contrast, in human clinical trials for breast augmentation, the concentration of ASCs in graft material may be increased two- to fivefold compared with non-manipulated lipoaspirates [32, 44]. Although there are many reports stating the clinical versatility of CAL for breast augmentation, none of these studies have employed a control group. Considering the previous studies, there is a lack of definitive evidence that fat grafting combined with ASCs is clinically efficacious for reducing the rate of resorption of the graft although the amount of liposuction needs to be twice compared with the standard fat grafting.

Another major issue of concern is oncogenic potential, although this may be more likely to be associated with breast reconstruction after mastectomy than cosmetic breast augmentation. Traditionally, postoperative calcification following fat grafting to the breast has been thought to compromise breast cancer screening; however, several studies have shown that there is no clear evidence that autologous fat transfer affects the efficacy of breast cancer screening or results in a delay of breast cancer diagnosis [45, 46]. Recent scientific attention has turned to whether fat grafting including ASCs could potentially convey an increased risk of breast cancer or cancer recurrence, although there has been no direct evidence with regard to fat grafting to the breast and an increased risk of cancer. Perrot et al. [47] presented a case report of a late, local recurrence of osteosarcoma following autologous fat grafting. In this case, the patient had the original surgical resection and neoadjuvant chemotherapy at 17 years of age for an osteosarcoma of the proximal humerus. Thirteen years after the initial treatment and 18 months following three sessions of autologous fat grafting to reconstruct the post-surgical defect, she presented with a tumor recurrence at the site of reconstruction. Although such a case, where the patient was thought to be in complete remission, might be rare, the growth of active tumor cells, not resting tumor cells, has been shown to be enhanced by ASCs [48]. Therefore, reconstructive procedures, including those for cosmetic purposes, utilizing CAL, should be postponed until there is no evidence of active disease, despite the fact that most studies have indicated that there is no correlation between fat grafting to the breast and an increased incidence of breast cancer or cancer recurrence [4951]. This recommendation is also supported by the ASPS Task Force stating that clinicians should “exercise caution when considering high risk patients” for autologous fat grafting to the breast (i.e., those with past personal or family history of breast cancer, BRCA-1 and BRCA-2) [5].


36.5 Future Directions


Clinical data have suggested that fat grafting to the breast, with or without ASCs, offers satisfactory results for patients undergoing cosmetic breast augmentation and correction following partial mastectomy. Basic science and clinical investigators are currently actively engaged in the field of adipose tissue and ASCs. Research suggests that ASC supplementation may be an effective clinical tool in the future, but additional data are needed to ensure that fat grafting or lipoinjection is performed in a safe and effective manner [52]. To optimize and validate fat grafting procedures, evidence-based studies that incorporate randomized controlled, prospective, multicenter trials are required to elucidate which factors positively influence clinical outcomes.


References




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Zhu M, Zhou Z, Chen Y, Schreiber R, Ransom JT, Fraser JK, Hedrick MH, Pinkernell K, Kuo HC. Supplementation of fat grafts with adipose-derived regenerative cells improves long-term graft retention. Ann Plast Surg. 2010;64(2):222–8.PubMedCrossRef


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Mar 20, 2016 | Posted by in General Surgery | Comments Off on Fat Grafting Supplemented by Adipose-Derived Stem Cells for Breast Augmentation

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