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A Big Fat Blow for the Stem Cell Literature: Major Paper Withdrawn

POSTED ON IN Latest News BY Chris Centeno

fat stem cell research

This past year, I was actually excited to add fat stem cells to my big annual review of the orthopedic stem cell literature. While a few small papers had been published, a big part of that literature was a huge data set by Michalek out of Eastern Europe, which purported to show that fat stem cells used for knee arthritis worked great. While I was a critic of the paper because the results seemed too good to be true, I felt it needed to be included in the discussion over bone marrow versus fat. However, this past week I learned that the paper had been withdrawn, which decimates the fat stem cell research literature.

The Back Story on Bone Marrow vs. Fat

While we have chiropractic-clinic stem cell seminar scams popping up all over, promising to regrow new knees with zombie (living-dead) amniotic tissue, real doctors who do this work have been arguing back and forth for the last decade about whether bone marrow or fat was better for orthopedic purposes. The fat-stem-cell crowd has argued that fat has more stem cells (please see video below as this is largely untrue) and that a liposuction is less invasive than a bone marrow aspirate (again untrue). Having said that, there has been a paucity of clinical studies on fat stem cells to date compared to much more on the use of bone marrow concentrate in orthopedics.

The Study That Seemed to Alter the Fat-Stem-Cell-Research Calculus

In 2015, a massive data set of knee and hip arthritis patients treated with both types of fat stem cell therapies (stromal vascular fraction, or SVF, which is illegal in the U.S.) and a fat graft was published by Michalek. This fat-stem-cell paper looked a bit strange to me, so I pointed out a few problems with the research methods. What was wrong?

First, the follow-up rate was ridiculously high. In any study, certain patients will be lost to follow-up, meaning that after a time, they fail to respond. This is unavoidable, but if the study is small, you can usually minimize the number of patients that don’t respond to your questionnaires. However, once the study gets to more than 100 patients, this can be tough. If the study gets to several hundred patients, it’s almost impossible. This study had more than a thousand patients, and the follow-up rate was much higher than you would expect. In fact, without involving the local police and SWAT unit to hunt people down who failed to fill out their outcome forms, it seemed suspiciously high.

Second, the results seemed too good. The study reported that a very high number of patients had fantastic results. In fact, that 91% of patients were classified as having greater than 50% improvement at one year after the injection. These numbers were much higher than any other publication on any published stem cell procedure. When digging into the paper, it wasn’t hard to see how this sleight of hand was accomplished. The physician authors got to make up 60% of the final outcome, while only 40% of the input came from the patient.

The Study Is Withdrawn

This past week, I went to look for the study to cite it in another work, and I found this:

micalek fat stem cell paper

Was the paper pulled from the journal for the problems I had identified, or was it something else? It’s likely we may never know for sure.

What I can say is that the withdrawal of this paper from the fat-stem-cell literature punches a huge gaping hole in the research base. For example, my 2017 version of the summary of fat-stem-cell research had 10,018 patients who had their results reported for any stem cell type to treat orthopedic injuries. Of that, 8,533 were patients treated with bone marrow stem cells. A whopping 1,128 of the 1,485 patients treated with other cell types were from the Michalek study. Subtract those patients, and the totality of non-bone-marrow-treated patients falls to 357 compared to 8,533 for bone marrow. In summary, take out the Michalek study, and the research on stem cells other than bone marrow used to treat orthopedic problems is almost insignificant.

The upshot? The withdrawal of the Michalek paper is a huge blow for the research on fat stem cells in orthopedics. Hopefully, more research will be published quickly to bridge the huge chasm of research support for fat stem cells compared to bone marrow!

9/12/17-I was contacted by the author of the above paper and it was republished here after being withdrawn by the editor of the initial publisher: . While the author and I disagree on outcome measurement, I do feel that this paper is a key one for the orthopedic adipose stem cell literature.



    Bob Eberhardt says

    Dr. Centeno,
    Local doctor (Western New York) has this on his website:
    Stem Cell Therapy is relatively new. Stem cells are unspecialized (undifferentiated) cells that are characteristically of the same family type (lineage). They retain the ability to divide throughout life and give rise to cells that can become highly specialized and take the place of cells that die or are lost. Stem cells can both renew themselves and create new cells of whatever tissue they belong to. Stem Cell Therapy is capable of regeneration, repairing, replacing and maintaining or enhancing organ function that has been lost due to:

    Congenital Abnormalities
    These stem cells for therapeutic use in humans most commonly come from bone marrow or adipose (fat) tissue. Some studies are showing fat cells are better than bone marrow cells in regenerating damaged cartilage such as seen in osteoarthritis of joints and degenerative discs. Stem cells, from your own fat has been shown in recent studies to facilitate cartilage growth in knee joints better that bone marrow derived stem cells (1).

    The newest use of stem cells from the patient’s own fat is a unique procedure using Lipogems, which is a fat harvest and then a fat transfer to the involved joint. This allows blood vessels to be maintained in the fat that have Pericytes on them which are the precursors to all stem cells. When injected in a joint the Pericytes are released from the blood vessels and produce stem cells with are then activated into regenerative stem cell that can call on cells from around the patient’s body to bring the healing cells necessary to stimulate the healing process.

    These stem cells have 2 main functions, immunologic and regenerative. Currently if you go to there are at least 426 studies underway for all types of diseases.

    If you are considering Stem Cell Therapy, remember that larger studies need to be done to determine if the outcomes justify the cost. Dr. Geraci completed a pilot study as the principal investigator looking at the efficacy and safety of Stem Cell Therapy in peripheral joints for osteoarthritis. This study was completed in October, 2015 and showed that it was both safe and efficacious in regenerating cartilage growth in the knee at 6 months on an MRI compared to the MRI done before treatment. MRI scans will be done at 1 and 2 years post treatment.
    1. Bean AC, et al: Chondrogenesis using MSC from bone marrow and fat. TERMIS, 2011.

    What's your take on this? Thanks! (I've had a Regenexx PRP procedure on my lumbar spine and it has definitely been an improvement.)


    Chris Centeno says

    Glad to hear there has been improvement! The biggest issue with the procedure being used on the website you shared is that Lipogems is not a stem cell procedure, it's a fat graft. This explains the difference: We actually couldn't find a paper published with the title listed. It may have been presented at a Conference and not published or published with a different title. We would certainly agree that MSC's are chondrogenic, but again the issue with this procedure is that it's not a stem cell procedure, so not chondrogenic.


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    About the Author

    Chris Centeno

    Christopher J. Centeno, M.D. is an international expert and specialist in regenerative medicine and the clinical use of mesenchymal stem cells in orthopedics. He is board certified in physical medicine as well as rehabilitation and in pain management through The American Board of Physical Medicine and Rehabilitation.…

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