Beyond laminitis: The potential of regenerative medicine to deliver better outcomes

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An illustration of the equine musculoskeletal diseases discussed in the just-published review and the harvest sites for bone marrow (from the sternum), adipose tissue (from the tail head) and blood (from the jugular vein) for mesenchymal stem cell (MSC) isolation, respectively, for platelet-rich plasma (PRP) and autologous conditioned serum (ACS) preparation. Image: https://doi.org/10.3390/ani11010234

More studies using regenerative medicine in a bid to improve the welfare of laminitic horses can be expected, according to the authors of a just-published review.

Regenerative therapies in the field of laminitis have gained more interest in recent years, Iris Ribitsch, Gil Lola Oreff, and Florien Jenner noted in their paper in the open-access journal Animals.

The common and painful hoof condition can occur due to any number of systemic or local insults, in either an acute or chronic form. The prognosis depends on the initiating cause and is generally favourable to poor.

Current treatment options are mainly limited to pain management, cryotherapy, hoof support, and, depending on the cause, treatment of the underlying disease.

“Since no curative treatment is available, high hopes are pinned on new regenerative treatment strategies,” the trio, from the University of Veterinary Medicine Vienna, noted in their review exploring the use of regenerative medicine for equine musculoskeletal diseases.

They described the use of mesenchymal stem cells (MSCs) in one study in an attempt to regulate the severity of the inflammatory response in the hoof.

Nine horses with chronic laminitis were injected three times with MSCs suspended in platelet-rich plasma through the palmar digital veins.

All horses in the study had been treated previously with conventional laminitis treatments without much success. MSCs derived from the patient, as well as other horses, were used without any complications.

“In the long term, a significant improvement could be noted in vascularity, structure, and function of the hoof.”

The review team noted that the distribution of MSCs injected into the lower limb might be improved by using different injection methods, such as into an artery rather than into a vein, potentially improving the therapeutic benefit.

Platelet-rich plasma, which contains high levels of growth factors and anti-inflammatory factors, can aid in regulating inflammation, decreasing pain and assist with the development of new blood vessels.

Due to those abilities, it has also been proposed as a therapeutic option for chronic laminitis.

“Although the literature reporting treatment of laminitis with platelet-rich plasma is limited to case reports, the results are encouraging,” Ribitsch and her colleagues noted.

Chronic laminitis patients reportedly showed improvement in comfort and hoof conformation after injection of platelet-rich plasma through the coronary band.

The trio noted that lameness caused by musculoskeletal disease is the most common diagnosis in equine veterinary practice.

Many of these orthopaedic disorders are chronic problems, for which no clinically satisfactory treatment exists.

Thus, there are high hopes for regenerative medicine, which aims to replace or regenerate cells, tissues, or organs to restore or establish normal function.

They noted that some regenerative medicine therapies have already made their way into equine clinical practice with promising but diverse results, mainly to treat tendon and cartilage problems, and degenerative joint disorders.

In equine practice, several regenerative therapies, such as MSCs, platelet-rich plasma, autologous conditioned serum and autologous protein solution, have been used for various musculoskeletal problems over the last decade.

“However, the field of regenerative medicine still has to live up to high hopes and expectations placed on it, both from a medical and financial viewpoint.”

The authors noted that large placebo-controlled studies are still scarce despite promising results from multiple experimental and preclinical studies, case reports and small randomised and controlled studies.

Regenerative medicine also faces several challenges, such as the lack of well-defined cells to be used as therapeutics and insufficient understanding of their mode of action. Some mechanisms involved, such as the interplay of growth factors, cytokines, proteinases, and cellular mediators, remain poorly understood.

“To exploit the full potential of tissues to heal, our understanding of how reparative processes are mediated and may be directed towards regeneration rather than scarring repair needs to be improved.”

The field of equine regenerative medicine involves much pioneering work, they noted, with variable treatment protocols using different routes of administration and/or dosages of cells, which may contribute to the discrepancies between promising experimental results and clinical effectiveness.

“Hence, intensive research efforts are still ongoing and required to find ways to exploit the maximal potential of regenerative medicine.”

The authors traversed the current knowledge around MSCs, autologous blood products and the various applications of regenerative therapies.

They noted that most of the applied regenerative therapies are still at an experimental state and patients are treated within the scope of clinical trials.

Looking to the future, they noted that models of tissue injury and naturally occurring regeneration have shown the importance of the immune response for tissue repair, highlighting the necessity to regulate inflammatory processes to aid regeneration.

“Traditional regenerative medicine focused on transplanting exogenously prepared cells or tissue while neglecting to consider the inflammatory and degenerative microenvironment.”

Novel approaches try to work with, not against biology, to create an environment to induce regeneration within the horse.

“To this end the genetic elements, regulatory pathways and specific cell populations that limit or allow intrinsic regeneration need to be identified to be able to use mammalian tissue development and regeneration as a blueprint to guide the development of novel regenerative therapies.”

Ribitsch, I.; Oreff, G.L.; Jenner, F. Regenerative Medicine for Equine Musculoskeletal Diseases. Animals 2021, 11, 234. https://doi.org/10.3390/ani11010234

The review, published under a Creative Commons License, can be read here

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