What is stromal vascular fraction or SVF?

When 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 2021.

What’s in this article

What is Stromal Vascular Fraction or SVF?  |   What cells are in SVF?   |   What about MSCs in SVF?   |   Lipogems vs. SVF   |   Is stromal vascular fraction a natural product?   |   Homologous use of stromal vascular fraction?   |   Looking ahead on stromal vascular fraction

What is Stromal Vascular Fraction or SVF?

SVF, stromal vascular fraction
SVF or stromal vascular fraction production methods. Knoepfler image.

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. They are very harsh.

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 both 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 (more below).

While most likely all the cells in SVF did mostly exist in the body fat from which they were extracted, 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 in a sense new kinds of cells with novel properties, whether good or bad.

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 stromal 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.”

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 they haven’t been proven safe and effective for particular applications in rigorous clinical trials. Nonetheless many clinics are selling unproven and non-FDA compliant SVF and other stromal vascular fraction therapy.

Meanwhile, in coming months in 2021 the FDA is poised to crack down more on the firms selling SVF injections.

References

25 thoughts on “What is stromal vascular fraction or SVF?”

  1. Gerard Malanga

    This post today,July 4, 2020 looks like a rerun on this same topic a year ago.
    We are now a study site for 2 FDA approved studies using SVF. One for knee IA and another for rotator cuff tear. This is in addition to 2 studies using MFAT in RTC tears in WC dependent spinal cord patients and a meniscal tear study. There appears to be great potential benefit in these treatments !

  2. Paul, great topic and questions. Glad to see fellow UC Davis researcher (UCD DVM and MPVM 1982)! I am a veterinarian with 35 year contract research experience doing human and veterinary research for FDA submissions. In veterinary medicine, we are in our final phase 3 FDA GCP clinical pivotal studies for an adipose stem cell product in dogs. As Dr. Rogers mentioned, we have used our veterinary data (collected since 2003) as preclinical support, including many GLP, GCP, and GTP studies and last week received IND approval for our first study of SVF in knee osteoarthritis in human. We are trying very hard to follow the pathway that FDA has provided. I have personally over 15 peer-reviewed regen med papers and book chapters and will continue to collect quality data with help from quality investigators like Dr. Rogers and Dr. Malanga. We support FDA continued crackdown on illegal clinics in the US.

  3. Gerard A malanga

    Regarding the those other clinics, I bet most THINK that they are fine, so yes they are likely continuing on their merry way. We need to find the best method to get those that are not compliant to be halted. I think the FDA has started on this hoping their actions will scare these other clinics into compliance. Those that are working with the FDA as Chris has noted should be the guide for anyone else hoping to use SVF. In addition, I have been a strong proponent of a national database registry and have started a company with Chris Rodgers to this: DataBiologics.com.

  4. Gerard A malanga

    Paul:

    It would be nice if you high-lighted the centers that are trying to do the right thing in this area i.e. clinical research. There has been some disparaging words written about “even Academic centers” getting involved in stem cell treatments. Shouldn’t we encourage these centers to properly determine the safety and efficacy of these treatments ?

    gm

    1. @Gerald, My impression is that very few are going the FDA compliant route. I’m currently looking into those that might be and if I can document that then I may do a post on it.

  5. Two issues here:

    1) I never have processed SVF in my clinic, although I have used MFAT for 3.5 years with good results to be published soon. FDA has regulated (and enforced with recent legal action) that processed SVF in the clinic is a biologic drug and must go through the IND process.

    2) I am medical director for a company that has received IND approval to study GMP processed SVF under an FDA / IRB approved clinical trial. Two other clinics in the US have received IDE from FDA to study SVF (not processed in GMP facility) under FDA / IRB approved clinical trials (Mayo clinic and Emory University).

    1. Thanks for clarifying that. For the MFAT, is that similar or roughly equivalent to lipo gems? Do you feel the stem cell component of the microfragments of fat tissue are the most important?

      1. Interesting question, but not enough evidence to answer, yet.

        There is evidence that MFAT (equivalent to Lipogems) contains pericytes, adventitial cells, adipose stem cells and others. The clinical challenge with MFAT is that we can not characterize the biologic in the office (cell count, secretome, viability, etc). With GMP processed SVF, we can do cell count, CD markers, viability, etc. This data will be correlated with the outcomes in our FDA approved clinical studies to help answer the question.

        1. Thanks for the info. Do you also find white blood cells including macrophages? I’m wondering how these cells might either be helpful or potentially cause issues after deployment of the MFAT.

          1. Limited published evidence on MFAT content, but there are some anti-inflammatory properties.

            Here are two articles worth reading:

            Long-Lasting Anti-Inflammatory Activity of Human Microfragmented Adipose Tissue.
            Sara Nava
            https://doi.org/10.1155/2019/5901479

            Higher Pericyte Content and Secretory Activity of Microfragmented Human Adipose Tissue Compared to Enzymatically Derived Stromal Vascular Fraction
            Bianca Vezzani
            https://doi.org/10.1002/sctm.18-0051

  6. Gerard A malanga

    SVF treatments are NOT compliant with FDA guidance and therefore not used by clinicians like Dr. Rodgers or at my center here in NJ.

    1. @Gerard,
      I wouldn’t be so sure. There are/were 100s of clinics deploying SVF on a daily basis. I doubt they all suddenly stopped.
      Do you think all those 100s did cease?
      Paul

  7. Christopher Rogers

    It’s important to understand the differences between: Adipose tissue, Lipoaspirate, Microfragmented adipose tissue (MFAT, such as Lipogems), GMP lab processed Stromal Vascular Fraction (SVF) and Cultured Adipose Stem/Stromal Cells (ASC).

    Each has a different cellular content, biologic effect and FDA regulation requirements.

    I recently wrote a review of the published peer-reviewed scientific evidence for SVF in orthopedic conditions.

    You can email me at [email protected] for a copy.

    1. Dear Dr. Rogers, I noticed you mentioned, GMP lab processed SVF, but do the clinics that use SVF really go through a GMP procdure to obtain GMP-grade material? I checked some clinics but I cannot find a reference to this anywhere – all I see is patients in their outdoor clothes having the adipose aspiration and then the SVF being prepared in a standard lab (but this could be for the cameras). Is there a database of approved GMP facilities in the US so that we can check for the clinics that have one?

    2. Does anyone know how many MSCs are in 50ccs of fat on average? I got quoted anywhere from 100,000 cells to 100 million cells, big difference!

      1. Both those numbers sound too extreme on either end.
        Depends on method, patient and location isolated from, but figures I’ve seen suggest yield is 0.5-1.0 million total cells/10cc of fat.
        However, most are not really MSCs and many will either die or are already dead so living cell #’s are lower.
        Someone who regularly does the procedure (I’ve never done it of course) may have a better sense.

        1. With our isolation procedure, we usually isolate 250.000 cells per g fat (~1,15 cc). This highly depends on the donor and the individual processing. It can vary from 10.000 to 1 Mio depending on lab and procedure.

          And, I agree with Paul, these total cells are a variable mixture. The amount of MSC really depends on your definition of MSC (at this point in time). If you follow minimum standards, e.g. triple staining for CD73, 90, 105, you end up at a max. of 1-5% MSC by flow cytometry. However, if you culture the cells afterwards, many of the non-triple positive become triple positive. We have not analyzed them after 1 day in culture, so I can’t say how many adherent cells you generate from the total cells.

          Besides, you also have to distinguish between lipoaspirate, fat phase and fat. Lipoaspirate is an emulsion that settles with time. The longer it stands, the more fat and buffer separate. Afterwards, the fat phase is usually washed and then the volume of isolated fat becomes smaller by approx. factor 2. So the questions is what others compare or what they relate the numbers to.

          Nicole

          1. Thanks for these details Nicole. I am particularly interested in the change in phenotype of the stem cells after isolation versus the phenotype in the tissue. From what you say I guess the cells have entered the cell cycle from quiescence (and have a very different transcriptome presumably).

            So after expansion in culture do you wait for them to become confluent and growth arrested before administration to patients or are the proliferating cells injected?

            Thanks for any help.

  8. Gerard Malanga

    Dr. Christopher Rodgers has provided a detailed lecture on the various Adipose terms that have been used and scientific evidence for them in the treatment of Orthopedic and other conditions. This lecture was given at the annual meeting of the Interventional Orthopedic Foundation. I encourage everyone to review this lecture and/or PDF of the lecture.

Leave a Reply