√ My Take As A Biologist On Us Stem Cell “Natural” Claim In Federal Court Case Endgame

It’s been less than a year since the FDA sued for a permanent injunction against a major stem cell clinic firm in Florida, but there has been much back and forth in court filings in the lawsuit between them and the firm, US Stem Cell.

Now the case is with the judge.

My prediction remains that the feds will prevail, but it seems worthwhile to look at some of US Stem Cell’s arguments. Note as a sort of disclaimer that I’m not an attorney so I’m approaching this as a stem cell scientist and I may miss some subtleties or even obvious elements of court matters.

For the purpose of examining some of US Stem’s tamat arguments, let’s look at the recent response item that I see in Pacer that the defendants filed. There are some notable arguments in there in that document which is titled, “DEFENDANTS US STEM CELL, INC., US STEM CELL CLINIC, LLC, AND KRISTIN C. COMELLA’S REPLY IN FURTHER SUPPORT OF THEIR MOTION FOR SUMMARY JUDGMENT.”

A surprisingly narrow, but important area of dispute in this case seems to be over the meaning of the word “such” as relates to the term HCT/P (human cellular and tissue product).

I’m not kidding.

The “such” language argument seems to be mostly centered on the main point about the stem cell product discussed below.

It seems to me that a key assertion by US Stem Cell is that their production of adipose stromal vascular fraction (SVF; see my drawing of how SVF is usually made and note that the way each firm including US Stem does this is somewhat different, but you get the gist) does not substantively change the material from its native state in the patient’s body. As such, US Stem claims that they are eligible for the same surgical procedure exception (SSP) that would in that hypothetical case potentially make their production and use of SVF outside the scope of FDA drug oversight authority.

For instance, US Stem writes the following in that recent court document (emphasis mine here and in all the quotes):

“The Defendants’ SVF Surgical Procedure thus fits well within the SSP Exemption. The plain language of the SSP Exemption exempts procedures that occur during a single sitting in which the human cell or tissue that is put back into the patient is not significantly altered from the form in which it naturally exists in the same patient’s body. That is what happens here; nothing more.”

In my view, US Stem is not right about this.

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 tamat SVF. Instead, SVF is a laboratory-manufactured product.

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.

US Stem writes about the purported natural state of SVF again in the same document:

“The “rinsing, cleansing, sizing, or shaping” affects only the tissue that is discarded, and not the tissue that is put back into the patient, which is what happens here. Because the SVF is unchanged from the time it is removed from the body (as part of the adipose tissue, some of which is discarded) until it is put back into the body, it remains “in the form removed from the body.” Dkt. No. 41-1 at 13. The SVF is, therefore, “such HCT/Ps.” 

And then US Stem asserts the natural state for SVF a third time, “Accordingly, the SVF cells naturally existing in an individual’s body at the time of removal constitute “such HCT/Ps” when implanted into the same individual’s body as part of the SVF Surgical Procedure.” (note the insertion of the word “cells” here, which is interesting).

In fact, the word “naturally” is used 3 times in this document.

No matter how many times it’s written, I personally don’t buy it even if some others may agree with the argument of SVF being a “natural” (minimally manipulated) product. At a very basic level one could say that if SVF was not significantly different than patient fat, if you are a stem cell clinic then why not just inject the unchanged fat?

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, secual 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.

However, I haven’t seen homologous use mentioned as much as things related to minimal manipulation overall including in this response document from the defendants. It may be that there’s some confusion over whether non-homologous use in the context of minimal manipulation could still be compatible with a SSP exception status. I’ve puzzled over that for bone marrow (see about 3/4 of the way down in this post) in the past, but my feeling was that for SVF that non-homologous use alone was sufficient to trigger drug classification based on FDA docs. It may be kind of a moot point if SVF is already a drug based on more than minimal manipulation, but adds to the basis for drug classification.

I’m curious, no matter what the verdict, how much the court will write in the judgment about the reasons behind her decision and how much biomedical science she will mention.

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√ Can Clinic Biz Us Stem Reboot After Losing Suit? Its Email To Customers More

The unproven stem cell clinic firm US Stem Cell Inc. is in a world of hurt.

If a federal judge says you can no longer sell your key commercial offering, how do you survive as a company? US Stem probably has been thinking about that possibility for months. Still, it’s not yet clear where the company goes from here now that this has become a reality.

Where do things stand looking ahead?

There’s financial pressure.

The company’s stock ($USRM) has been a penny stock for a while, but lately it’s been sub-one cent and trending downward. I’m not a stockbroker, but even I know that can’t be good.

I’m also not an attorney, but I can figure out that patient lawsuits against the company have also probably taken a toll over the last few years, mostly via confidential settlements.

The federal district judge who imposed the permanent injunction on USRM also indicated all stock of the unapproved fat stem cell drug product the company had been making, called stromal vascular fraction (SVF) must be destroyed. In my view this is another big hit to the company. Many customers appear to have paid USRM to bank and store SVF in cryofreezers for them. Now that a judge has ordered that material destroyed due to the decisions the company made, will USRM have to refund the stem cell banking fees to the customers? It seems like a possibility and if not, then there could be a lot of angry customers.

USRM sent out an email to customers about this specific kasus (see at right). My sense is that the email reflects a hope that the court might allow customers to obtain their SVF if enough complain. However, since SVF is a drug that wasn’t made in an FDA-compliant manner, to me this seems like a long shot. The court has to realize that if released to customers, some of them would be likely to have the unapproved drug injected by other physicians. Others might even try self-injection in rare instances. Is a court really going to facilitate that use of an unapproved drug product?

USRM leader Kristin Comella published an opinion piece in the conservative Washington Times a few days ago, arguing USRM’s case about the FDA and the court decision. As a stem cell biologist I disagree with a lot in the piece.

This sentence, for instance, seems to me to have some hype in it, “While no medical procedure is without risk, dozens of peer reviewed papers have demonstrated safety and efficacy. Patients are getting better; they’re getting out of wheelchairs, off pharmaceutical medications and breathing on their own.”

There is also no mention of the patients who went to USRM and apparently lost vision.

I’m wondering if USRM will appeal the court decision and perhaps spend the big money required going down that path. Or might they instead focus on reinventing their offerings? Both?

Overall, it seems that USRM may try to switch over to either bone marrow-related or other types of injections to take the place of the SVF.

Will the switch save the company?

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√ What Exactly Is Stromal Vascular Fraction (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?

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 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.

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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