September 26, 2020

The Niche

Knoepfler lab stem cell blog

What exactly is stromal vascular fraction (SVF)?

SVF stromal vascular fractionWhen people discuss “fat stem cells” they usually mean something called “stromal vascular fraction” or SVF. While references to fat or adipose stem cells can sometimes mean non-SVF materials, these days adipose SVF gets the most attention. But, does anyone have a clear picture of this biologic? Fortunately, it’s starting to come more into focus in recent years and I’ve updated this post in May 2020.

What exactly is Stromal Vascular Fraction (SVF)?

In a nutshell, stromal vascular fraction is a cellular extract made in a laboratory from fat. While methods to produce the SVF extract vary, the basic idea is that the wide variety of cells within fat tissue are separated from the actual gloppy fat tissue itself. Those cells are then concentrated to make SVF.

That’s about it.

However, getting cells out of fat requires a molecular sledgehammer. This extraction process generally uses something called an enzyme, most often one called collagenase. Enzymes like these chew up proteins that run through the fat tissue and connect with cells.

Imagine your spaghetti and meatballs are stuck together in a giant web of sticky cheese. You are on a paleo diet or something so you only want the meatballs. In this analogy the enzyme used to make SVF would release the meatballs (the cells) from the spaghetti and over-abundant pounds of cheese. Except with cells within fat tissue, they are tiny and sparsely present throughout.

The end product of SVF is not a naturally occurring substance. While all the cells in SVF did mostly exist in the body fat, they weren’t together. Also the exposure of the cells to the enzyme can change their behavior and inherent nature in some ways. The stress of the process could even generate cells with new properties.

It’s not well-understood. In principle SVF could be made from almost any tissue to isolate its stromal and vascular cells. It’s basically just done almost always with fat these days.

What cells are in SVF?

Many different cells end up in SVF.

The exact numbers and types are going to vary a lot from patient to patient. Also, lab or clinic making the SVF preparation and the individual person doing it will influence what comes out of it. Overall, some cells are likely to be in every stromal vascular fraction prep. Fibroblasts will make up a good number of SVF cells too. It’s important to note that there different kinds of fibroblasts as well. There may even be some primitive fibroblasts that are more like progenitor cells.

A few fat cells or adipocytes will be there along with some fat cell progenitors called pre-adipocytes.

Blood vessel cells will also be in SVF, including endothelial cells and smooth muscle cells. Also in SVF are really interesting cells called pericytes that hug the exterior of blood vessels. They may have some stem cell like properties, perhaps being able to make smooth muscle cells and a few other types.

There are also going to be actual white blood cells in SVF too including macrophages.

The National Cancer Institute (NCI) has its own definition of stromal vascular fraction here, but I think they are a bit generous on their description of the known functional properties.

There are likely to be fragments of many cells in SVF preps too depending on how it is made and purified. Those could pose risks.

What about MSCs in SVF?

Wait a minute, you might say, what about mesenchymal stem and stromal cells (MSC)?

Often folks use the terms SVF and MSCs interchangeably. So aren’t MSCs in fat? There are some MSCs in SVF, but not as many you might think based on the rhetoric out there by some. Many “MSCs” may be more like a cross between stromal and stem cells, which is why some folks think the acronym MSC should stand for, “mesenchymal stromal and/or stem cells.”

Lipogems vs. SVF

Something called lipogems are also made from fat. They sometimes get discussed together with SVF and MSCs. Certain folks have suggested that lipogems basically functionally are fat stem cells, but that’s not clear. Here are a few articles in Pubmed on lipogems.

There are many fat products out there and some universities and large academic medical centers are starting to do trials on various preps. For example, you can see a YouTube video from Mayo above by Jay Smith, M.D. I’m not endorsing the Mayo Clinic’s regenerative medicine activities, but I think it’s an interesting video.

Is stromal vascular fraction a “natural” product?

There has been some back and forth about whether SVF is a natural product. This could have big implications because the real debate here is whether SVF as used by clinics has been more than minimally manipulated (aka not natural). I wrote a post about this in regard to the US Stem Cell federal court case and here’s a key passage from my post:

“My main reasoning is that SVF does not naturally exist in a patient’s body. Yes, fat with associated cells and vasculature, does exist in the patient’s body, but it’s not the same as the final SVF. Instead, SVF is a laboratory-manufactured product.fat quote

It might be helpful here to compare SVF to bone marrow aspirate, which is generally considered minimally manipulated as typically prepared because the marrow cells are basically the same inside the body as they are outside the body in the aspirate that is then injected into patients.”

Is there such a thing as homologous use of stromal vascular fraction?

Another issue I raised in that post is the question of homologous use of SVF.  This means using a product in a way that is similar to the original tissue inside the body. For instance, homologous use of kidney stem cells would only probably be possible to treat kidney disease. In this sense, SVF could only be used in a homologous manner to treat a disease related to fat, such as facial wasting. From my blog post:

“Beyond the more than minimal manipulation issues discussed above, there’s also the consideration of homologous use (or lack thereof). If a product is used in a non-homologous manner (e.g. SVF being used to treat non-fat-related health conditions like neurological conditions, many orthopedic issues, eye problems, sexual issues, etc.) that can also make it by definition a drug product requiring premarket approval too. It seems to me at least, that many of the reported applications of SVF are likely to be non-homologous.”

Looking ahead on stromal vascular fraction

Overall, I believe that cellular medicine products from fat have real potential, but haven’t been proven safe and effective for particular applications in rigorous clinical trials.

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