Do stem cells for pain make any sense?

stem-cells-for-pain

stem-cells-for-painDoes it make any sense scientifically or medically to use stem cells for pain?

I’m skeptical in most cases today.

The whole idea of stem cells for pain has been on my mind for a number of reasons.

For one thing, more stem cell clinics are marketing unproven stem cell therapies at a high price specifically for pain relief lately.

People are even having conferences on this concept. See the email ad I got yesterday on one such conference below

Is there any FDA-approved stem cell-based treatment for pain? Even one? Nope.

In Leigh Turner’s and my paper last year on stem cell clinics, we found in our data analysis that marketing of stem cells for pain was the 2nd most common claimed condition (see Figure 2B below). Even though this indication is unproven as safe or effective, clinics charge thousands and sometimes tens of thousands of dollars per intervention for this

Circling back, does it even make any sense scientifically that stem cells could relieve pain specifically?

How could this work if it can?

stem-cells-for-painA damaged tissue such as a knee-joint, if repaired by stem cells, could be less painful.

Maybe it could.

But again RCTs have not been done to prove this approach is safe and effective for repair, let alone pain relief.

In theory stem cells might be able to repair or replace dysfunctional nerves themselves leading to less pain, but most commercial offerings in this area aren’t using the right kind of stem cells. It’s not clear to me how, for instance, adipose or bone marrow stem cells could repair nerves. They are not programmed to do this.stem-cell-treatments-pain

Repairing a damaged spine with stem cells could also lead to less pain. But how do you get the right stem cells to the right place in the spine and have them do the right thing (and not the wrong thing) to fix the spine in such a way to reduce pain? Not simple, but possible.

There are more than 300 clinical trials for stem cells at least somehow related to pain. Hopefully some of these will provide clarity on this hot topic.

22 Comments


  1. Any comment about why the segment of Dr. Oz Expose on Stem Cell Clinics aired
    February 14, 2017 (Season 8, Episode 102) on True Crime was taken down?
    Only the Laci Peterson Murder segment remains. All web sites that mentioned
    the segment have been removed or stripped of any reference. This is scary!
    I lead a support group for neuropathy and so far have seen no evidence that
    injecting your belly fat stem cells cures anything.


  2. Dear Paul,
    I have been given multiple infusions of autologous totipotent stem cells intranasally for CNS-associated neurological pain and multiple infusions of autologous plutipotent stem cells systemically for musculoskeletal pain generated by my Stage-IV SLE. In each instance, the neurological and musculoskeletal pain subsided for at least 2-3 months following the stem cell infusions. Granted, a sample size of 1 is not statistically significant. But it does suggest the potential for a clinical trial in this area.


    • @Edward,
      That sounds really dangerous! Pluripotent cells can form teratoma and other tumors potentially. Weren’t you concerned about that risk?
      Why would intranasal administration help with muscle or nerve pain in other parts of the body? Is there FDA approval for what you are receiving?


      • Dear Paul,
        The default state for the naturally occurring adult pluripotent stem cells used in my case is quiescence. They do not spontaneous differentiate, as do pluripotent ESCs or induced pluripotent stem cells. These naturally-occurring stem cells have been extensively studied and published in 2nd- and 3rd-tier peer-reviewed journals, both in animal models and in IRB (Institutional Review Board)-approved clinical trials, in which I am a participant. I trust the PI (principal investigator) with my life. In my case, the pluripotent stem cells were given by IV (intravenous)-infusion. The naturally-occurring totipotent stem cells, because of their uniquely small size, are the ones that were given intranasally. After deposition on the olfactory epithelium at the roof of the nose, the totipotent stem cells migrate between the olfactory epithelial cells (without the use of hyaluronidase [an enzyme that dissolves the mucus {snot}] or without the use of mannitol [that raises the local osmotic pressure to shrink the olfactory epithelial cells to create spaces between the cells]), then the totipotent stem cells migrate along the olfactory rootlets, through the cribriform plate in the skull, along the olfactory nerves into the cisterns surrounding and within the brain and spinal cord, thus bypassing the blood-brain barrier. From there they can travel to damaged tissues within the CNS (brain and spinal cord) and repair damage. In my case my spinal nerves, L1-L4 (lumbar nerves at levels 1-4 of the lumbar vertebrae), have fibrosed to my vertebral column causing excruciating lower back pain. Also, I have neuropathic pain in my lower extremities due to spontaneous muscle contractions. Both the back pain and lower extremity pain has been alleviated to some extent with multiple infusions of naturally-occurring stem cells by intranasal and systemic IV delivery. The PI is involved in IRB-approved clinical trials to generate numbers of participants sufficient to apply for IND (investigational new drug) through the FDA.


    • Edward, could you clarify – what cells are you calling autologous totipotent stem cells”? I thought only the zygote and the first few cells of the blastomere were totipotent.


        • Hi Paul, the possibility that it was VSELs also crossed my mind, but how could any clinician propose to administer such things, when they haven’t been isolated, characterized or cultured? Edward posts very clear descriptions of his responses to treatments and I thought he might give us a clue to exactly what the cells are – if autologous adult stem cells, then they are not likely to be totipotent, unless manipulated in culture.


      • Dear Archie Cochran,
        The PI (principal investigator) identified totipotent stem cells as a lineage-uncommitted stem cell that would form ALL somatic cells of the body and will also form the gametes, such as spermatogonia. He defines pluripotent stem cells as a lineage-uncommitted stem cell that will form ALL somatic cells of the body, but will NOT form the gametes. He has also defined germ layer lineage stem cells, i.e., ectodermal stem cells as a stem cell that has committed to the ectodermal germ layer lineage and will only form cells of ectodermal origin, mesodermal stem cells as a stem cell that has committed to the mesodermal germ layer lineage and will only form cells of mesodermal origin, and endodermal stem cell as a stem cell that has committed to the endodermal germ layer lineage and will only form cells of endodermal origin. His lab has identified these endogenous stem cells in amphibians (adult terrestrial salamanders), reptiles (Komodo dragon), avians (chickens and Waddel crane), non-human mammals (mouse, rat, rabbit, cats, dogs, sheep, goat, pigs, spotted bear, cow, horse), and humans. They have derived clonal populations of cells derived from a single cell in avians, mice, and rats and performed extensive characterization analyses. They developed animal model systems for Parkinson’s disease, cardiovascular disease, pulmonary disease, and artificial pancreatic islet organoids. They performed an IRB-approved clinical trial for Parkinson’s disease. Representative publications from his lab are: Anat Rec 276A:75-102, 2004; Cell Biochem Biophys 40:1-80, 2004; J Neurological Disorders, 2:1, 2013; and MOJ Orthop Rheumatol 1(4): 00019, 2014. He is listed on http://www.researchgate.com. All his publications are downloadable as pdfs.


      • Dear Archie Cochran,
        The principal investigator has never been associated with Maurice Ratajczak’s laboratory (VSELs) that I can tell from his publication list. The totipotent stem cells that are used have been induced to form 67 different identifiable differentiated cell types across all three primary germ layer lineages and have been induced to form spermatogonia (MOJ Orthop Rheumatol 1(4): 00019, 2014). While 68 is not close to the 220 different cell types located in the body, I believe the number of differentiated cells they induced from their totipotent stem cells (68) is based more on the number of individual objective assays in their laboratory rather than the absolute differentiative potential of the stem cells. I am inclined to believe that if they had objective assays for more differentiated cell types then more cell types would be identified being formed from their totipotent stem cells, pluripotent stem cells, and germ layer lineage stem cells. The endogenous autologous stem cells used for human treatments (i.e., totipotent stem cells, pluripotent stem cells, and mesodermal stem cells) are fresh isolates that have never been cultured. In fact, from harvest to infusion of segregated stem cells takes just 2-4 hours processing time (J Neurological Disorders, 2:1, 2013).


        • @Edward,
          I’m not at all convinced these cells are a real thing. The papers are not conclusive. It also makes no sense from a developmental biology perspective that the adult human body would have pluripotent or totipotent stem cells in it. In adult mice (admittedly not the same as humans) inducing pluripotency causes tumors and death.


          • Dear Paul,
            You need to converse with the principal investigator (PI) directly with respect to the validity of his research. I believe he answered a few of the ten questions you posted concerning stem cells, so you already have his contact information. Also, I would suggest checking out all of his research on http://www.researchgate.com. I may not have provided the appropriate references to give you a better understanding of the scope of his research. He started his research in 1975 studying limb regeneration in adult terrestrial salamanders, where he discovered the adult stem cells. And why does it not make any sense for the adult human body to harbor these stem cells? From what I have read there are 220 differentiated cell types in the human body. It would make more sense from a logistics and engineering standpoint to have one or two cell types located within every tissue in the body that have the potential to regenerate, replace, and/or repair those tissues. To the best of my limited knowledge, the cells identified and isolated by the PI are naturally occurring endogenous stem cells. These cells are normally quiescent in the body and only become involved in regeneration, replacement, and repair after overt tissue damage. While induction of differentiated cells with Yamanaka’s embryonic gene constructs can cause them to become pluripotent, one wonders if all the regulatory controls have also been added to the cells during the induction process. Your comment concerning the induction of pluripotency causing tumors and death, suggests maybe not. So personally, I would rather receive stem cells that naturally occur in my body rather than cells that have been genetically manipulated in the laboratory, at least until scientists have worked out all the problems associated with the induced pluripotent stem cells.


  3. Mesoblast is running a Phase III clinical trial for back pain due to disc degeneration and it is placebo controlled: http://www.mesoblast.com/product-candidates/spine-orthopedic-disorders/chronic-discogenic-low-back-pain I’m skeptical they will get good results.

    When it comes to pain, everybody should read the work of Dr. John Sarno, a genius, IMHO, who started out as an orthopedic surgeon but couldn’t see how what he was doing with conventional orthopedic medicine was actually helping patients with pain. He also was puzzled by why there was no consistent correlation between patient pain and what showed up on an x-ray or MRI. This lead him to the concept of TMS or Tension Myositis Syndrome. The pain is real but the cause is psychological and curable once understood. https://en.m.wikipedia.org/wiki/John_E._Sarno Many who have been helped by him including Howard Stern and a friend of mine who avoided back surgery. All should be aware of his theory of pain and read at least one of his books.


    • @WST,
      I think you are likely right about Mesoblast’s trial, but could you say more about why you think this?
      I wasn’t familiar with Sarno’s work so I’m going to take a look.
      Thanks as always for your comments. – Paul


      • I didn’t think the Phase II results were impressive and if you understand and believe Dr. Sarno’s work on pain you will understand that much of pain is mentally based even if the pain is real. TMS involves the brain’s removal of oxygen from tissue as mental defense system causing the pain as a distraction. Once you understand the MOH of TMS the pain disappears. For these reasons, not even mentioning the placebo effect, I think Mesoblast will have a difficult time showing efficacy for back pain. Too many variables to pain. Read up on SARNO!!


  4. You wrote: “A damaged tissue such as a knee-joint, if repaired by stem cells, could be less painful…But again RCTs have not been done to prove this approach is safe and effective for repair, let alone pain relief.”

    Happily, an RCT (n=30) studying the effects of MSCs on knee repair was published in the Journal of Translational Medicine in August of last year.

    https://www.ncbi.nlm.nih.gov/pubmed/27565858

    “CONCLUSIONS:
    The single intraarticular injection of in vitro expanded autologous BM-MSCs together with HA is a safe and feasible procedure that results in a clinical and functional improvement of knee OA, especially when 100 × 10(6) cells are administered. These results pave the way for a future phase III clinical trial.”

    This isn’t necessarily the only published RCT of its kind, just an example of one that a very minimum amount of effort turned up.


  5. This is a very misleading article. Let’s take one of the most common knee surgeries (knee arthroscopic meniscectomy). Patient presents to an orthopedist with knee pain. The cause of the pain is determined to be caused by a torn meniscus. The torn piece is removed in surgery, and the knee pain resolves. By your rationale, the surgery repaired the nerve damage?

    Maybe the mechanical issue resolved by removal of the tear, and the adult synovial fluid derived stem cells improved the inflammation. These same stem cells derived from the bone marrow. It is also not true to state there Is no science behind Bone Marrow or Adipose derived stem cells.


    • Maybe you are claiming these things because you represent Induced Pluripotent Stem Cells which has a financial incentive to debase other stem cell derivatives.


    • Agreed, there is science behind bone marrow and adipose-derived stem cells. One only has to read articles by Arnold Caplan, Catherine Verfaillie, and Maurice Ratajczak for bone marrow-derived stem cells and Adam Katz for adipose-derived stem cells to see that is the case.


    • You’re wrong – adult synovial fluid derived stem cells are not the same stem cells as those from bone marrow – the clue is in the name 😉

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