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  Discussion on Review of Equine Stem Cell Therapy
Author Message
Member:
wgillmor

Posted on Tuesday, Feb 19, 2013 - 6:12 pm:

Dr. O,

I found the following in Equine Disease Quarterly, July 2012, Volume 21, Number 3, by Dr. Wesley Sutter, Lexington Equine Surgery & Sports Medicine Lexington, Kentucky. Would you agree?

A recent television documentary about stem cell fraud in human medicine posed this question: “Are stem cells the ‘snake oil’ of the 21st century?” The documentary focused on the growing, highly lucrative business of fake stem cell cures that reportedly resulted in a federal investigation. With public awareness of failures in stem cell therapy newly heightened, it is important to reflect on our situation in equine medicine.

Stem cell treatments for horses have been available since at least 2005. They have become a relatively common treatment for many equine musculoskeletal injuries, often promoted as a panacea for bone, cartilage, and tendon healing. Internet testimonials and videos claiming miraculous cures in individual patients with neurologic and laminitic conditions have fueled often irrational exuberance and extravagant expectations. To date, no published controlled clinical studies show efficacy in use of stem cell treatment for any of the conditions being treated. In fact, the two most recent studies evaluating stem cells, one in a tendonitis model and the other in a cartilage defect model, showed no significant difference with their use, either clinically or histologically, as compared to controls in which stems cells were not used.

Papers have touted stem cells’ miraculous ability in the laboratory; however, once administered to the patient, the situation changes dramatically. A multitude of poorly understood factors likely mitigate the activity of stem cells once administered. Patients have their own stem cells, and wound healing is modulated through a complex array of molecular events, including cytokine signaling. Equally important, stem cell culturing methods and source tissues (bone marrow, adipose, fetal cells, and cord blood) vary among laboratories.

Are stem cells from any source good for everything? Most scientists would agree this is unlikely, and future treatment will likely involve selection of stem cells with a particular phenotype or genetic modification in order to treat a specific disease. The most basic questions remain. How do we know that the stem cells from a particular laboratory or process are not terminally differentiated fibroblasts that have absolutely no biologic effect? How do we know they will persist in the wound environment long enough to have a biologic effect? How do we know they are of the correct phenotype? Plasticity, differentiation into the desired tissue type, and/or feeder effects may be present in the petri dish; however, mechanisms once injected into the patient have yet to be elucidated.

With a virtual absence of oversight and regulations, equine veterinary use of stem cells has dramatically increased, resulting in over a dozen university, private enterprise, and private practices culturing allogeneic and/or autologous stem cells for use in horses. Expert opinion, testimonials, and anecdotal evidence are not in short supply. When coupled with a lack of good clinical evidence or even a good understanding of potential mechanisms, they threaten to pull stem cell therapies into the abyss often occupied by nutraceuticals and supplements.

Stem cells hold promise. However, clinical acceptance has greatly outpaced the scientific evidence. That evidence needs to be supplied, with both professional organizations and those producing stem cells taking the lead. Finally, practitioners using stem cells also have a responsibility to accurately represent these therapies to their clients.

(Note: Material published in the Quarterly is not subject to copyright. Permission is therefore granted to reproduce articles, although acknowledgment of the source and author is requested.)

Thanks,
Wiley
Member:
gramsey1

Posted on Tuesday, Feb 19, 2013 - 6:42 pm:

https://www.ca.uky.edu/gluck/q/2012/jul12/Q-Jul-2012.pdf
Moderator:
DrO

Posted on Wednesday, Feb 20, 2013 - 7:33 am:

Hello Wiley,
I agree with this statement which summarizes the article and agrees with the article associated with this area:

Stem cells hold promise. However, clinical acceptance has greatly outpaced the scientific evidence. That evidence needs to be supplied, with both professional organizations and those producing stem cells taking the lead. Finally, practitioners using stem cells also have a responsibility to accurately represent these therapies to their clients.

DrO
Member:
wgillmor

Posted on Wednesday, Feb 20, 2013 - 9:14 am:

Hello DrO,

Do you agree with the statement:

To date, no published controlled clinical studies show efficacy in use of stem cell treatment for any of the conditions being treated.

Thanks,
Wiley
Moderator:
DrO

Posted on Thursday, Feb 21, 2013 - 6:52 pm:

No Wiley, the statement is incorrect. If you will use the National Library of Medicine button in the article you will find supportive studies. Currently I remain unconvinced of the cost / benefit and do not routinely recommend the procedure.
DrO
Member:
wgillmor

Posted on Thursday, Feb 21, 2013 - 7:56 pm:

Hello DrO,

Sorry to be a pest, but I searched the abstracts for the word "controlled" looking for controlled studies. Here is what I found:

J Transl Med. 2009 Apr 24;7:29. doi: 10.1186/1479-5876-7-29.
Non-expanded adipose stromal vascular fraction cell therapy for multiple sclerosis.
Riordan NH, Ichim TE, Min WP, Wang H, Solano F, Lara F, Alfaro M, Rodriguez JP, Harman RJ, Patel AN, Murphy MP, Lee RR, Minev B.
Source
Medistem Inc, San Diego, CA, USA.
...The effectiveness of stem cell-based therapies and most tissue engineering concepts has not been demonstrated sufficiently in controlled clinical trials in equine patients to be regarded as evidence-based medicine...Controlled, well-designed studies are needed to move this new equine research field forward.

Can Vet J. 2008 Oct;49(10):1009-17.
Concepts for the clinical use of stem cells in equine medicine.
Koch TG, Berg LC, Betts DH.
Source
Department of Biomedical Sciences, University of Guelph, Guelph, Ontario N1G 2W1.
...Controlled, well-designed studies of the basic biologic characteristics and properties of these cells are needed to move this new equine research field forward. Stem cell research in the horse has exciting equine specific and comparative perspectives that will most likely benefit the health of horses and, potentially, humans.

Disabil Rehabil. 2008;30(20-22):1752-8. doi: 10.1080/09638280701788241.
Mesenchymal stem cell therapy for equine tendinopathy.
Smith RK.
Source
Department of Veterinary Clinical Sciences, The Royal Veterinary College, North Mymms, Hatfield, Hertfordshire, UK.
...Autologous implantation of mesenchymal stem cells into tendon injuries may therefore improve clinical outcome although definitive proof of efficacy, which is still lacking, will require randomized controlled trials.

The last of these is probably the most positive reference I've found, but is admittedly not a controlled trial. Can you point me to anything I missed? If you want to tell me I'm being lazy and should go and read the relevant articles rather than relying on a key word search of the abstracts, that's OK too.

My motive in this is that my Trakehner gelding has a torn medial collateral ligament (diagnosed by blocking and ultra-sound) and has not come sound on stall rest. (Not surprising since it is almost impossible to keep him quiet.) My vet mentioned stem cell therapy as a possibility (without much enthusiasm.) I'm trying to find out if it is likely to do anything besides lighten my wallet and make me feel I've tried everything.

Thanks,
Wiley
Member:
mdelton

Posted on Thursday, Feb 21, 2013 - 10:00 pm:

For what it's worth, my horse had a badly torn medial meniscus and had arthroscopic surgery at Cornell. They suggested stem cells so I went ahead and had them drawn and cultured and injected during the surgery. These were from the sternum.

That was 8 months ago and he was U/S at 6 months and the meniscus still had a lot of missing material. He was not the best patient in terms of rearing up in his stall during the stall confinement and bucking and rearing in the very small turnout at 3 months. Also, he got away from me twice on hand walks and was only 2/5 lame before and 3-4/5 lame after.

The good news at 8 months is that I don't see him resting the "bad" leg (before, he would rest that leg a lot). He isn't yet sound but he is in a larger, yet small turnout and will run around a bit and that extra movement doesn't make him any less sound. I'm certainly not convinced that the stem cells have played any positive role, nor do I think they hurt anything but my wallet. And as you say, Wiley, at least I feel I tried "everything" but if I had it to do over, I would have insisted on using the adipose derived stem cells rather than the bone marrow ones. There was an interesting discussion in a webinar from The Horse:

https://www.thehorse.com/videos/webcasts/31255/stem-cell-therapy-for-orthopedic-i njuries

in which Dr Ross Rich discusses Stem Cell Therapy

I'm still hoping that Mother Nature will help my horse recover enough to be trail ridden.

Mary
Member:
gramsey1

Posted on Friday, Feb 22, 2013 - 5:44 am:

We have a horse boarding at our place, with a badly torn suspensory. She was injured at another barn and injected March or 2012. Moved here in May, she is a model patient. I have been transporting her to the clinic every 6-8 weeks since. Things were looking better for awhile. Then, improvements seemed to stop or reverse. Her owner is paying for a second round . . .
Owners are hoping for a return to the hunter ring. I am unconvinced that it is helping. I hope for pasture sound, which she seemed to be six months ago.
https://www.vetmed.ucdavis.edu/ceh/docs/special/Pubs-SuspBrochure-bkm-sec.pdf
It is difficult for both the horse and the owner. She is a pretty little Quarterhorse.
Member:
rtrotter

Posted on Friday, Feb 22, 2013 - 9:04 am:

I have been reading this thread with interest because I know the subject of stem cells has been around for a while. And as far as I can see the jury is still out. I had a horse I was racing several years ago and decided against stem cells because of the cost and the uncertainty of whether or not they would work in her specific case. Her tendon was very badly damaged and the prognosis was not good on getting her back to the races.

The first thing I did, when it happened was research everything I could find on rehabbing seriously bowed tendons and the treatments to heal them. I thought this mare was talented enough to deserve as long as it took to get her well.

After all the research and reading, I decided to try Tom Ivers approach to the bowed tendon problem. In case you do not know Tom Ivers, He was the father of Interval training for all types of horses, his writing, based on scientific studies, is written so anybody can understand it. He utilizes sports medicine principles(people and horses)in his works.

I used his information to heal my horses tendon.

Some of the things I did, were based on my mare's personality and the fact that she had always spent her nights outside and that she would have kicked the walls down if I left her inside. I felt that was counterproductive to her healing.

So, out she went. She stayed much quieter, did not run around and because her routine stayed basically the same, except for jogging everyday for the first week or so. She moved at her own speed.

Other than right after the initial injury, she was not given any anti-inflammatories. The fill in her tendon was almost gone after a week or so( the injury was still there, which was monitored every month)

Based on the information from Tom Ivers. I used a tens machine during the six or so hours she was in her stall during the day. The electrodes are attached above the knee and affect the nerves that run down through the leg and through the tendons and simulate constant movement and keeping the scar tissue from forming in a way that retards the healing. In other words as the leg healed the tendon began to not show(based on the ultrasounds)the typical defects that one would see with scar tissue across the injury site. It instead looked healed and healthy.

As far as her exercise protocol went. This mare went back to work( very slowly) about a week after the injury. First walking and then limited jogging/towing until she was back up to 5 sound miles a day took about 6 weeks. Still on the tens machine every day. If she showed any signs of lameness( she showed very little). I backed off to where she was comfortable. I understood that it was the reformation(tearing and healing) of the scar tissue that caused this. She started back training and made it back to the races 8 months after the original injury( Sound!) with the tendon 98% healed. Not sure I could have gotten 100% healed based on the severity of the injury to begin with.

To sum up.
1) Horse was not kept on stall rest, but was kept moving
2) Used a tens machine
3) Did not have time off, was kept turned out during rehab
4) Used controlled exercise
5) backed off small amounts when lameness was observed.
6) Build back up to normal work over a long period of time

For those of you that have tried it all and do not want to go with surgery or stem cells, you should look into Tom Ivers research on these problems. Also for suspensories the name of the machine used was an EMS machine, does the same thing as a Tens machine but for larger areas. Both these machines are also used on people.

Dr. O please feel free to move this under alternative therapies if necessary.

Thanks
Rachelle
Member:
wgillmor

Posted on Friday, Feb 22, 2013 - 11:51 am:

I had a look at the video Mary mentions above (https://www.thehorse.com/videos/webcasts/31255/stem-cell-therapy-for-orthopedic-i njuries)

The video provides one of the best examples I've seen as to why we need controlled studies. The same information could as well have been presented to advocate a particular rehab regimen with a side note that all cases where the owner did not accept stem cell therapy were excluded from the study. Instead it was advocacy for stem cells with all horses where the owner did not accept the rehab regimen excluded. A controlled study would have helped us sort out what was cause and what was incidental.

That is not to say that Dr. Ross should have done anything but what he did. He's a practicing veterinarian and is obligated to give horses under his care what he believes is the best treatment with consideration of the owner's resources and wishes.
Moderator:
DrO

Posted on Saturday, Feb 23, 2013 - 1:26 pm:

Wiley all of your references above are 4 to 5 years old. Did you look at the Pub Med site? You will find controlled studies there.
DrO
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