Cell-Assisted Autologous Fat Grafting

The contention that cell-assisted lipotransfer confers some kind of advantage over the conventional method of transplanting autologous fatty-tissue aspirates has very few high-quality studies to support it. This is the conclusion that Soraya Grabin and colleagues reach in their comprehensive and thorough study (described on the following pages), on the basis of a systematic literature review and a critical assessment of the current evidence regarding the “;cell-assisted” procedure (1).

Only a few informative studies

Since its description in 2001 by Patricia Zuk and colleagues (2), the use of processed lipoaspirates has aroused much interest not only among clinical and basic-science researchers, but also among practicing physicians who do not perform research. The reason for this enthusiastic reception is that, unlike stem-cell fractions derived from bone marrow, processed lipoaspirates can be acquired easily and in large quantities. The widespread but ill-considered promotion of this technique, rightly criticized by Grabin et al., must be seen in the light of the very small number of published clinical trials yielding any useful information about its efficacy.

No reliable data are available about the safety of cell-assisted lipotransfer in patients who have been treated for cancer. Because such patients often have soft-tissue defects, they make up a large percentage of the target population for reconstructive procedures on the soft tissues (3).

For more than three decades now, autologous fat transplantation (lipotransfer, sometimes called “;lipofilling”) has been an established method in plastic surgery (4). It is used to fill in small tissue defects, e.g., after breast reconstruction or in the treatment of other kinds of scars. In 2006, Matsumoto et al. reported higher survival rates for transplanted lipoaspirates after stem-cell enrichment in a xenogenic murine model (5).

In Germany, cell-assisted lipotransfer is not currently part of routine clinical practice for regulatory reasons, because the fatty-tissue isolates that it employs have not yet been definitively classified. The important questions affecting the regulatory classification are, first, whether the process of generating these isolates should be designated as industrial or as insufficiently known, and, second, whether the process involves a substantial alteration of the tissue. Moreover, the properties of the tissue isolates that are to be transplanted need to be further defined; they would most fittingly be designated as “;advanced therapy medical products” (ATMP), as they consist of cells that are supposed to have beneficial autocrine and paracrine effects at the implantation site, rather than act as adipocytes themselves (Article 2 [1] a [EC] No. 1394/2007).

Intense interaction of stem-cell fractions with tumor cells

The potential stimulating effects of stem cells on the formation of connective, epidermal, and stromal tissue, and their potential modulating effects on inflammation and angiogenesis, need to be further studied in clinical trials under controlled conditions. This is because the efficacy of cell-assisted lipotransfer has not yet been adequately documented; the findings of the basic studies performed to date, involving animal experimentation, do not suffice for this purpose (6).

Oncological safety must become a major focus of clinical research on cell-assisted lipotransfer, because the available experimental data suggest that stem-cell fractions interact intensely with tumor cells (7).

For now, therefore, stem-cell fractions should be used in combination with lipoaspirates only under the controlled conditions of clinical trials. Even more importantly, further high-quality trials need to be performed on lipotransfer itself (without any stem cells added) and on the use of stromal fatty-tissue isolates in reconstructive surgery.

To meet the twin goals of safety and efficacy, both of these techniques and any potential future combinations should be required, even now, to meet the standards of established stem-cell therapy.

A further problem

The report by Grabin et al., from the Cochrane Center and the Department of Plastic Surgery at the University Medical Center Freiburg (Germany), illustrates a further problem hindering the generation of robust data in reconstructive surgery. Amid a multitude of heterogeneous applications, Grabin and colleagues identified only a single randomized, dual-armed, blinded trial on 18 patients with craniofacial microsomia, which yielded grade II–III evidence (8). No long-term outcomes have ever been reported. Small patient numbers for highly restricted indications are a deficiency that has been criticized in reconstructive surgical trials in the past and that can only be overcome with randomized, multicenter trials. These, in turn, can only be conducted with adequate financial support.

The outlook for patient safety

The medical devices that enable cell-assisted lipotransfer through automated tissue processing should not just be required to have CE certification; a further precondition for their approval ought to be the documented clinical efficacy of the technique. The current reality is different, unfortunately, as Grabin et al. rightly point out. The safety of future uses of adipogenic stem cells therefore still lies in the hands of clinical researchers, who must work diligently to develop more effective and less burdensome reconstructive techniques. Persistent risks lie in the gray area in which cell-assisted lipotransfer is aggressively promoted and performed for commercial reasons only.