Stem Cell Therapy - the improved diagnostics available to treat lameness

Article by Jackie Zions (interviewing Dr. Koenig)

Prevention is the ideal when it comes to lameness, but practically everyone who has owned horses has dealt with a lay-up due to an unforeseen injury at some point. The following article will provide tools to sharpen your eye for detecting lameness, review prevention tips and discuss the importance of early intervention. It will also begin with a glimpse into current research endeavouring to heal tendon injuries faster, which has obvious horse welfare benefits and supports horse owners eager to return to their training programs. Dr. Judith Koenig of Ontario Veterinary College (OVC) spends half of her time as a surgeon and teacher with a strong interest in equine sports medicine and rehabilitation, and the other half as a researcher at the OVC.

Lameness is a huge focus for Koenig, whose main interest is in tissue healing. “I think over the past 20 or 30 years we have become very, very good at diagnosing the cause of lameness,” says Koenig. “In the past, we had only radiographs and ultrasound as a diagnostic tool, but by now most referral centres also have MRI available; and that allows us to diagnose joint disease or tendon disease even more. We are much better now [at] finding causes that previously may have been missed with ultrasound.” 
Improvements in diagnostics have resulted in increased ability to target treatment plans. With all the different biologics on the market today, Koenig sees a shift in the management of joint disease with more people getting away from steroids as a treatment.

The following list is excerpted from Equine Guelph’s short course on lameness offered on TheHorsePortal.ca. It outlines the different diagnostics available:

When asked for the latest news on research she has been involved in, Koenig proclaims, “I'm most excited about the fact that horses are responding well to stem cell treatment—better than I have seen any response to any other drug we have tried so far!”

Koenig has investigated the use of many different modalities to see if they accelerate tissue healing and has studied which cellular pathways are affected. Two recent collaborative studies have produced very exciting findings, revealing future promise for treating equine osteoarthritis with stem cell therapy.  

In a safety study, Koenig and her team at the Ontario Veterinary College have shown equine pooled cryopreserved umbilical cord blood, (eCB) MSC, to be safe and effective in treatment of osteoarthritis.  

“These cells are the ones harvested from umbilical cord blood at the time of foaling and then that blood is taken to the lab and the stem cells are isolated out of it,” explains Koenig. The stem cells are then put through a variety of tests to make sure they are free of infectious diseases. Once given a clean bill of health, they are expanded and frozen. 
The stem cells harvested from multiple donors of equine umbilical cord blood [eCB, (kindly provided by eQcell), MSC] were compared to saline injections in research horses. “This type of cells is much more practical if you have a cell bank,” says Koenig. “You can treat more horses with it, and it’s off the shelf.” There were no systemic reactions in the safety study. Research has also shown no different reactions from sourcing from one donor or multiple donors.  

In the second study, 10 million stem cells per vial were frozen for use in healing OA from fetlock chips in horses that were previously conditioned to be fit. After the fetlock chip was created, exercise commenced for six more weeks, and then osteoarthritis was evaluated by MRI for a baseline. Half the horses were treated with the pooled MSC stem cells, and the control group received saline before another month of exercise. Then MRI and lameness exams were repeated, and arthroscopy was repeated to score the cartilage and remove the chip.

Lameness was decreased and cartilage scores were improved in the group that received stem cell therapy at the time of the second look with arthroscopy.

Many diagnostics were utilised during this study. MRIs, X-rays, ultrasounds and weekly lameness evaluations all revealed signs of osteoarthritis in fetlock joints improved in the group treated with (eCB) MSCs. After six weeks of treatment, the arthroscopic score was significantly lower (better cartilage) in the MSC group compared to the control group. 

“Using the MRI, we can also see a difference that the horses treated with stem cells had less progression of osteoarthritis, which I think is awesome,” says Koenig. “They were less lame when exercised after the stem cell therapy than the horses that received saline.”

This research group also just completed a clinical trial in client-owned horses diagnosed with fetlock injuries with mild to moderate osteoarthritis changes. The horses were given either 10 million or 20 million stem cells and rechecked three weeks and six weeks after the treatment. Upon re-evaluation, the grade of lameness improved in all the horses by at least one. Only two horses presented a mild transient reaction, which dissipated after 48 hours without any need for antibiotics. The horse’s joints looked normal, with any filling in the joint reduced.
There was no difference in the 18 horses, with nine given 10 million stem cells and the other nine 20 million stem cells; so in the next clinical trial, 10 million stem cells will be used.

The research team is very happy with the results of this first-of-its-kind trial, proving that umbilical cord blood stem cells stopped the progression of osteoarthritis and that the cartilage looked better in the horses that received treatment. The future of stem cell therapy is quite promising!
Rehabilitation
Research has shown adhering to a veterinary-prescribed rehabilitation protocol results in a far better outcome than paddock turn out alone. It is beneficial for tendon healing to have a certain amount of controlled stimulation. “These horses have a much better outcome than the horses that are treated with just being turned out in a paddock for half a year,” emphasises Koenig. “They do much better if they follow an exercise program. Of course, it is important not to overdo it.”

For example, Koenig cautions against skipping hand-walking if it has been advised.  It can be so integral to stimulating healing, as proven in recent clinical trials. “The people that followed the rehab instructions together with the stem cell treatment in our last study—those horses all returned to racing,” said Koenig.  

“It is super important to follow the rehab instructions when it comes to how long to rest and not to start back too early.”

Another concern when rehabilitating an injured horse would be administering any home remedies that you haven't discussed with your veterinarian. Examples included blistering an area that is actively healing or applying  shockwave to mask pain and then commence exercise.

Prevention and Training Tips
While stating there are many methods and opinions when it comes to training horses, Koenig offered a few common subjects backed by research. The first being the importance of daily turnout for young developing horses.  

Turnout and exercise
Many studies have looked at the quality of cartilage in young horses with ample access to turn out versus those without. It has been determined that young horses that lack exercise and are kept in a stall have very poor quality cartilage.
Horses that are started early with light exercise (like trotting short distances and a bit of hill work) and that have access to daily paddock turnout, had much better quality of cartilage. Koenig cited research from Dr. Pieter Brama and similar research groups.

Another study shows that muscle and tendon development depend greatly on low grade exercise in young horses.  Evaluations at 18 months of age found that the group that had paddock turnout and a little bit of exercise such as running up and down hills had better quality cartilage, tendon and muscle.  

Koenig provides a human comparison, with the example of people that recover quicker from injury when they have been active as teenagers and undergone some beneficial conditioning. The inference can be made that horses developing cardiovascular fitness at a young age stand to benefit their whole lives from the early muscle development.

Koenig says it takes six weeks to regain muscle strength after injury, but anywhere from four to six months for bone to develop strength. It needs to be repeatedly loaded, but one should not do anything too crazy! Gradual introduction of exercise is the rule of thumb.

Rest and Recovery
“Ideally they have two rest days a week, but one rest day a week as a minimum,” says Koenig. “I cannot stress enough the importance of periods of rest after strenuous work, and if you notice any type of filling in the joints after workout, you should definitely rest the horse for a couple of days and apply ice to any structures that are filled or tendons or muscles that are hard.” 

Not purporting to be a trainer, Koenig does state that two speed workouts a week would be a maximum to allow for proper recovery. You will also want to make sure they have enough access to salt/electrolytes and water after training.

During a post-Covid interview, Koenig imparted important advice for bringing horses back into work methodically when they have experienced significant time off.
“You need to allow at least a six-week training period for the athletes to be slowly brought back and build up muscle mass and cardiovascular fitness,” says Koenig.  “Both stamina and muscle mass need to be retrained.”

Watch video: “Lameness research - What precautions do you take to start training after time off?” https://www.youtube.com/watch?v=zNHba_nXi2k

The importance was stressed to check the horse’s legs for heat and swelling before and after every ride and to always pick out the feet. A good period of walking is required in the warmup and cool down; and riders need to pay attention to soundness in the walk before commencing their work out.

Footing and Cross Training
With a European background, Koenig is no stranger to the varying track surfaces used in their training programs. Statistics suggest fewer injuries with horses that are running on turf. 

Working on hard track surfaces has been known to increase the chance of injury, but delving into footing is beyond the scope of this article.

“Cross training is very important,” says Koenig. “It is critical for the mental and proper musculoskeletal development of the athlete to have for every three training days a day off, or even better provide cross-training like trail riding on these days." 

Cross-training can mitigate overtraining, giving the body and mind a mental break from intense training. It can increase motivation and also musculoskeletal strength. Varied loading from training on different terrain at different gaits means bone and muscle will be loaded differently, therefore reducing repetitive strain that can cause lameness.

Hoof care
Whether it is a horse coming back from injury, or a young horse beginning training, a proficient farrier is indispensable to ensure proper balance when trimming the feet. In fact, balancing the hoof right from the start is paramount because if they have some conformational abnormalities, like abnormal angles, they tend to load one side of their joint or bone more than the other. This predisposes them to potentially losing bone elasticity on the side they load more because the bone will lay down more calcium on that side, trying to make it stronger; but it actually makes the bone plate under the cartilage brittle.  

Koenig could not overstate the importance of excellent hoof care when it comes to joint health and advises strongly to invest in a good blacksmith. Many conformational issues can be averted by having a skilled farrier right from the time they are foals. Of course, it would be remiss not to mention that prevention truly begins with nutrition. “It starts with how the broodmare is fed to prevent development of orthopaedic disease,” says Koenig. Consulting with an equine nutritionist certainly plays a role in healthy bone development and keeping horses sound.

Assessment of historical worldwide fracture & fatality rates and their implications for thoroughbred racing’s social licence

Article by Ian Wright MRCVS

Racing’s social licence is a major source of debate and is under increasing threat. The principal public concern is that racing exposes horses to significant risk of injury including catastrophic (life-ending) injuries of which fractures are the commonest cause. The most recent studies in the UK indicate that fractures account for approximately 75% of racecourse fatalities. Recent events highlight the need for urgent stakeholder discussion, which necessarily will be uncomfortable, in order to create cogent justification for the sport and reliant breeding industry.

A necessary prelude to discussion and debate is an objective assessment of risk. All and any steps to reduce risks and mitigate their impact are important and must be embraced by the horseracing industry (and quite possibly all other horse sports). To begin this, a here and now assessment is important: put simply, does the price paid (risk) justify the benefit (human pleasure, culture, financial gain, employment, tax revenue, etc). Objective data provides perspective for all interested parties and the voting public via their elected representatives, who ultimately provide social licence, with other welfare issues—both human and animal—on which society must pass judgement. 

The data in Tables 1 to 12 report a country by country survey of fracture and fatality rates reported in scientific journals and documented as injuries/fatalities per starters. It may be argued that little of the data is contemporary; the studies range from the years 1980 to 2013. However, the tabulated data provided below is the most up to date that can be sourced from independently published, scrutinised scientific papers with clear—albeit sometimes differing—metric definitions and assessable risk rates.

In assimilating and understanding the information, and in order to make comparisons, some explanatory points are important. The first, and probably the most important, is identification of the metric. Although at first glance, descriptor differences may appear nuanced, what is being recorded massively influences the data. 

These include fatality, catastrophic injury, fracture, orthopaedic injury, catastrophic distal limb fracture, fatal musculoskeletal injury, serious musculoskeletal injury, and catastrophic fracture. The influence of the metric in Japanese racing represents the most extreme example of this: ‘fracture’ in the reporting papers included everything from major injuries to fragments (chips) identified after racing in fetlocks and knees, i.e. injuries from which recovery to racing soundness is now an expectation.  At the opposite pole, studies in other countries document ‘catastrophic’, i.e. life-ending fractures which have a substantially lower incidence. The spectrum of metric definitions will all produce different injury numbers and must be taken into account when analysing and using the data. 

Studies also differ in the methods of data collection that will skew numbers in an undetermined manner. Some only record information available at the racecourse, others by identifying horses that fail to race again within varying time periods, horses requiring hospitalisation following racing, etc. The diagnostic criteria for inclusion of horses also vary between reports: some document officially reported incidents only, some are based only on clinical observations of racecourse veterinary surgeons, while others require radiographic corroboration of injuries. 

From a UK perspective, the data is quite robust in concluding that risks differ significantly between race types. The majority of fractures that occur in flat racing, and between obstacles in jump racing, are the result of stress or fatigue failure of bone. They are not associated with traumatic events, occur during high speed exercise, are site specific and have repeatable configurations. In large part these result from a horse’s unique athleticism: in the domesticated species, the thoroughbred racehorse represents the pinnacle of flight-based evolution. Fractures that result from falls in jump racing are monotonic—unpredictable, single-event injuries in which large forces are applied to bone(s) in an abnormal direction. 

This categorisation is complicated slightly as fatigue failure at one site, which may be bone or supportive soft tissue, can result in abnormal loads and therefore monotonic fracture at another. The increased fracture rate in jump racing is explained in part by cumulative risk. However, it is complicated by euthanasia of horses with injuries with greater post injury commercial value and/or breeding potential that might be treated. Catastrophic injuries and fatality rates in NH flat races are most logically explained by a combination of the economic skew seen in jump racing and compromise of musculoskeletal adaptation.

Racing surface influences both injury frequency and type. Studies in the UK have consistently documented an increased fatality rate and incidence of lower limb injury on synthetic (all weather) surfaces compared to turf.  Although risk differences are clear, confounding issues, such as horse quality and trainer demographic, mean that the surface per se may not be the explanation. In the United States, studies reporting data from the same geographic location have produced mixed results. In New York, these documented greater risks on dirt than turf surfaces; while a California study found no difference, and a study in Florida found a higher risk on turf. A more recent study gathering data from the whole of the U.S. reported an increased risk on dirt surfaces. Variations in the nature of injury between surfaces may go some way toward explaining fatality differences.

Much has been done to reduce recognisable risk factors particularly in jump racing; but in the UK, it is likely (for obvious data supported reasons) that it will come under the greatest scrutiny. The incidence of fractures and fatalities in flat racing are low, and the number of currently identified risk factors are high. Over 300 potential influences have been investigated, and over 50 individual factors demonstrated statistically are associated with increased risk of catastrophic injury. 

The majority of fractures occurring in flat racing (and non-fall related fractures in jump racing) are now also treatable, enabling horses to return to racing and/or to have other comfortable post-racing lives. 

The common public presumption that fractures in horses are inevitably life-ending injuries is a misconception that could readily be remedied. An indeterminate number of horses are euthanised on the basis of economic viability and/or ability to care for horses retired from racing. On this point, persistence with a paternalistic approach is a dangerous tactic in an educated society. Statements that euthanasia is ‘the kindest’ or ‘best’ thing to do, that it is an ‘unavoidable’ consequence of fracture or that only ‘horsemen understand or know what is best’ can be seen as patronising and will not stand public scrutiny. 

At some point, data to distinguish between horses euthanised as a result of genuinely irreparable injuries and those with fractures amenable to repair will become available. Before this point is reached, the consequences require discussion and debate within the racing industry.

Decisions on acceptable policies will have to be made and responsibility taken. In its simplest form, this is a binary decision. Either economic euthanasia of horses, as with agricultural animals, is considered and justified as an acceptable principle by the industry or a mechanism for financing treatment and lifetime care of injured horses who are unlikely to return to economic productivity will have to be identified.  The general public understands career-ending injuries in human athletes: These appear, albeit with ongoing development of sophisticated treatments at reducing frequency, in mainstream news. 

Death as a direct result of any sporting activity is a difficult concept in any situation and draws headlines. Removal of the treatable but economically non-viable group of injuries from data sets would reduce, albeit by a currently indeterminate number, the frequency of race course fatalities. However, saving horses' lives whenever possible will not solve the problem: it will simply open an ethical debate viz is it acceptable to save horses that will be lame? In order to preserve life, permanent lameness is considered acceptable in people and is not generally considered inhumane in pets. Two questions arise immediately: (i) How lame can a horse be in retirement for this to be considered humane? (ii) Who decides? There is unquestionably a spectrum of opinion, all of which is subjective and most of it personal. It will not be an easy debate and is likely to be complicated further by consideration of sentience, which now is enshrined in UK law (Animal Welfare (Sentience) Act 2022); but it requires honest ownership of principles and an agreed policy.

For the avoidance of doubt, while the focus of this article and welfare groups’ concerns are on racecourse injuries, those sustained in training follow a parallel pathway. These currently escape attention simply by being, for the most part, out of sight and/or publicity seeking glare. 

Within racing, there is unquestionably a collective desire to minimise injury rates. Progress has been made predominantly by identification of extrinsic (i.e. not related to the individual horse) risk factors followed by logical amendments. In jump racing (monotonic fractures), obstacle modification, re-siting and changing ground topography are obvious examples of risk-reducing measures that have been employed. 

In flat racing progress has involved identification risk factors such as race type and scheduling, surface, numbers of runners, track conditions etc which have guided changes. However, despite substantial research and investment, progress in identification of intrinsic (ie relating to the individual horse) risk factors is slow. While scientifically frustrating, a major reason for this is the low incidence of severe fractures: this dictates that the number of horses (race starters) that need to be studied in order to assess the impact of any intervention is (possibly impractically) high. Nonetheless, scientific justification is necessary to exclude a horse from racing and to withstand subsequent scrutiny.

Review of potential screening techniques to identify horses at increased risk of sustaining a fracture while racing is not within the scope of this article, but to date none are yet able, either individually or in combination, to provide a practical solution and/or sufficiently reliable information to make a short-term impact. It is also important to accept that the risk of horses sustaining fractures in racing can never be eliminated. Mitigation of impact is therefore critical. 

When fractures occur, it is imperative that horses are evaluated to be given the best possible on course care. This may, albeit uncommonly be euthanasia. Much more commonly, horses can be triaged on the course and appropriate support applied before they are moved to the racecourse clinical facility for considered evaluation and discussion. The provision of fracture support equipment to all British racecourses in 2022 marked a substantial step forward in optimising injured horse care.

Neither racing enthusiasts nor fervent objectors are likely to change their opinions. The preservation of social licence will be determined by the open-minded majority who lie between: it is the proverbial ‘man on the street’ who must be convinced. The task of all who appreciate horse racing's contributions to society and wish to see it continue is to remain focussed on horse welfare, if necessary to adjust historical dogmas, absorb necessary costs and to encourage open, considered, honest (factually correct) risks versus benefits discussion.