In the last two posts (When Fat Hits the Regulatory Fan: Mechanical Disruption of Adipose Tissue with the Lipogems System Part One andWhen Fat Hits the Regulatory Fan: Mechanical Disruption of Adipose Tissue with the Lipogems System Part Two), I reviewed a situation involving a 510(k)-cleared device/kit for mechanically disrupting a patient’s adipose tissue (i.e., the Lipogems System, see (When Fat Hits the Regulatory Fan: Mechanical Disruption of Adipose Tissue with the Lipogems System Part One for a link to the clearance letter) and how I thought there was a conflict with the description of what can be done to a lipoaspirate and still have the process meet the standard of “such HCT/P” described in the recently issued Same Surgical Procedure Exception Guidance (see Same Surgical Procedure Exception Guidance: What Does “Such HCT/P” Really Mean? Part One links and additional information). I would like to turn my attention to the kit itself and the material produced by the Lipogems System—what I refer to as fuzz balls—and some things to consider before becoming a fuzz baller.
If you go to the Lipogems website (http://lipogems.eu/lipoaspiration-system.html ) and look under “System” you will find the following statements:
The Lipogems® method consists of a single-use kit for the lipoaspiration, processing and deployment of adipose tissue.
The entire process is carried out in one surgical step.
Through a minimal enzyme-free manipulation in a sealed, sterile device, there is a gradual reduction of the adipose clusters and the elimination of oily and hematic residue with a pro-inflammatory content.
The entire process is performed with immersion in a saline solution which makes it possible to minimize any trauma to the cellular products.
An important feature of the Lipogems® product is its ability to maintain intact stromal vascular niches which contain mesenchymal cells and perycites.
The Lipogems® product obtained this way is a micro-fractured non-expanded adipose tissue intended for autologous use.
The objective of the Lipogems® product is to favor the natural regenerative process of tissues and it is used in numerous pathologies.
I didn’t edit anything, so the grammatical construction/composition comes directly from Lipogems. The impression I got from reading these words is that you can use the Lipogems System for anything you might think of, since there are a number of phrases that are meant to be soothing to physicians working in the USA, including the phrases: “minimal enzyme-free manipulation”; “non-expanded”; “lipoaspiration, processing and deployment of adipose tissue”; and “The entire process is carried out in one surgical step.” In addition, we are informed that saline is used to “minimize trauma” to the “mesenchymal cells and perycites (sic)”. What self-respecting physician eager to offer adipose tissue-derived autologous therapy wouldn’t want to provide their patients with non-traumatized stem cells?
The problem is, it isn’t obvious to me that the FDA is keen on physicians using the Lipogems System for supporting the “natural regenerative process of tissues and it is used in numerous pathologies”, unless Lipogems is referring just to situations in which fat grafting is a standard of care. Notice, however, that the term “fat grafting” doesn’t appear in their statements, yet, that is what the indications for use issued in the 510(k) letter are limited to.
But let’s assume that I have lost my regulatory bearings and I want to do the rumba with my patients’ adipose tissue. What am I producing? If you explore a bit on their website, and based on their statements listed above, you will be producing de-clustered adipose tissue, which retains intact progenitor cell-containing vascular niches. The image that came to mind when I first read about the Lipogems System is one of liposomes, which are fairly well-defined bilayer vesicles produced by mechanical agitation of different fat-containing materials. But the more I thought about the “micro-fractured” fat tissue, I realized that the term liposome wasn’t really correct. So, I come up with the term fuzz ball as a more appropriate aid in visualizing what is being produced with the kit. The beat-up fat tissue yields particles, which I can’t imagine are a uniform size, although there is some filtration involved. Perhaps more importantly, the composition of the cellular components will depend on a number of factors, some of them being patient-dependent, while others will depend on how muscular the person is who is shaking the patient’s lipoaspirate. In other words, I don’t see how this system can provide much in the way of a consistent physical composition.
Despite the claims that the output of their kit contains viable progenitor cells, especially since they pay attention to the health and welfare of these stem cells by the use of saline, there really isn’t an easy way to find out about the progenitor cells present in fuzz balls. While I am familiar with a wide variety of techniques for characterizing biological materials containing cells, fuzz balls present a few obvious challenges:
- If the fuzz balls aren’t uniform in size it is hard to count the particles with any accuracy. For example, I have had a lot of experience counting cells by eye and if the fuzz balls aren’t uniformly sized a visual count will be futile.
- While I haven’t seen an electron micrograph of a fuzz ball preparation, I can’t image that the micro-fractured particles will be composed of a single particle suspension, since fat is notoriously sticky, so the fuzz balls probably will agglomerate.
- Lipoaspirate tissue contains a mix of adipocytes and connective tissue remnants, including microvascular structures. Thus, any cells present will be dispersed over the entire particle, inside and out. It probably will be very difficult to count nucleated cells when they are spread over, around and through a fuzz ball.
- Most of the stains and dyes used to assess viability of nucleated cells will partition into the tissue remnants and the lipid vesicles of intact adipocytes. Consequently, I don’t see how an accurate cell viability could be assessed on fuzz ball preparations.
One important point I would like to make, despite my reticence to tell healthcare professionals how to practice medicine, although some might consider it obvious, is that fuzz balls shouldn’t be injected intravenously. Also, you might consider not injecting fuzz balls intraosseously, given the high density of vascular structures located in bone marrow depots. As long as I am lecturing, one other concern I have with fuzz ball treatments is the presence of connective tissue remnants that could be injected into a tendon or a ligament. Why is that an issue, since it is autologous, after all? Tendons and ligaments are relatively avascular tissues, so a hunk of connective tissue embedded in a tendon might not be reabsorbed in a timely manner due to reduced vascular access for macrophages and granulocytes. The presence of this type of inclusion body might delay or limit repair and restoration to a normally functioning tendon or ligament.
I will finish my review of the Lipogems System in the next post, including what I think are the limited options physicians might have in using it in the future in the USA.