Step towards tendon regeneration

Scientists have taken a step towards the goal of regenerating damaged tendons with the discovery that embryonic stem cells (ESCs) can produce “artificial tendon” in the presence of inflammation.

Researchers at the Animal Health Trust (AHT) in Newmarket studied the ability of three different populations of equine tendon cells (tenocytes) to produce “artificial tendon” in tissue culture. They grew tenocytes derived from ESCs, foetal tendon and adult tendon, and studied the effect of inflammatory markers on the process.

The superficial digital flexor tendon is the most frequently injured tendon in the horse. With conventional treatment, a damaged tendon will heal with fibrous tissue impairing its elasticity.  This results in reduced performance and a substantial risk of re-injury.

Regenerative medicine aims to replace the damaged tissue with tendon fibres that are as near normal as possible. This has led to the use of stem cells, which have the potential to differentiate into different cell types.

Stem cells can be implanted into the damaged tendon with the intention that they will differentiate into tenocytes and produce replacement tendon fibres. However, the inflammatory environment that exists in the healing tendon - mediated by signalling molecules (cytokines) such as interleukin-1β (IL-1β) -   may interfere with the stem cells’ growth.

The work at the AHT shows that the surface receptors of ESC-derived tenocytes differ from those of tenocytes derived from foetal or adult tendon. This makes them less responsive to IL-1β and so less affected by inflammation.

They found that adult and foetal tenocytes, when cultured in collagen gel in the presence of IL-1β produced artificial tendon that was less elastic than normal. In contrast ESC-derived tenocytes were not affected by IL-1β.

 “We were able to demonstrate that these tendon cells express different levels of receptors for inflammatory proteins on their surface” explained Dr Gebbie Guest, Head of Stem Cell Research at the AHT.

“This means that these stem cells may provide a useful source of cells for clinical transplantation into the injured tendon as they are unlikely to suffer any negative effects from being placed into an inflamed environment.”

The research team are now looking to further studies to understand how the ESC-derived tenocytes protect themselves from inflammation. This may allow them to develop drug treatments that could limit the damage to tendon cells after an injury.

For more details, see:

A novel mechanism for the protection of embryonic stem cell derived tenocytes from inflammatory cytokine interleukin 1 beta

Alyce McClellan, Richard Evans, Cheryl Sze, Shohei Kan, Yasmin Paterson & Deborah Guest

Scientific Reports (2019) Vol 9, Article number: 2755

Galloping not such hard work

Recent research has found that horses do less work moving through their environment than has been reported previously.

Earlier studies have estimated the external work of the moving horse from measurements taken using techniques such as 3D motion analysis. Now, researchers from the Royal Veterinary College (RVC) have used force plate technology to measure the external work of galloping in racehorses. The study has been published in the journal Biology Letters.

This new research, conducted by academics working in the RVC’s Structure and Motion Lab, measured the forces exerted by the horse on the ground. Sensors were buried under a section of the racing surface at the British Racing School in Newmarket. A professional jockey then rode seven thoroughbred racehorses over this specialist equipment, allowing the researchers to measure directly the external mechanical work of galloping by measuring the forces they exerted on the runway.

Sensors were buried under the track surface

The RVC’s study produced lower values than those previously reported for external work (the work a horse needs to do to move relative to its environment) in galloping horses. Estimated via different methods, those previously reported high external work values are at odds with the fact that horses evolved to move at high speeds over long distances. A high external work value would make moving over long distances much harder. The RVC’s new results support that thinking.

The research team were then able to calculate the apparent muscle efficiency of galloping horses by combining the external work values from this study with published values for metabolic work (the conversion of food into energy used by muscles) and internal mechanical work (how much work is needed to move the limbs relative to the body). They found that the horse’s efficiency values were between 37-46%.

The researchers expect that the findings will provide useful insight into the movement of racehorses and will contribute details towards explaining how racehorses can gallop so efficiently over long distances.

Commenting on the unique methodology of the study, Dr Zoe Self Davies, Postdoctoral Research Associate at the RVC, said: “This was really challenging data to collect and, to our knowledge, it is the first time high speed galloping force plate data have been collected from such a large animal.”

For more details, see:

External mechanical work in the galloping racehorse

Z. T. Self Davies, A. J. Spence and A. M. Wilson.

Biology Letters (2019) vol 15

doi.org/10.1098/rsbl.2018.0709

Why do zebras have stripes?

It has been a topic of debate for many years. Suggestions have included camouflage, confusing predators, thermoregulation… 

There is increasing evidence that the black and white stripes help limit attack by blood-sucking flies, although how that happens is not yet clear. Recent work from the University of Bristol, GB and UC Davis, California, USA, has provided a possible explanation.

Professor Tim Caro, Dr Martin How and colleagues have been investigating the behaviours of tabanid horse flies around captive zebras and domestic horses on a farm in North Somerset, using video analysis techniques.

Their new study has shown that stripes don't deter horse flies from a distance, with both zebras and domestic horses experiencing the same rate of circling from the flies. However, video analyses revealed differences in approach speed, with horse flies failing to slow down on approach to zebras, which is essential for a successful landing.

Professor Tim Caro, Honorary Research Fellow from the University of Bristol's School of Biological Sciences, said: "Horse flies just seem to fly over zebra stripes or bump into them, but this didn’t happen with horses. Consequently, far fewer successful landings were experienced by zebras compared to horses."

Dr Martin How, Royal Society University Research Fellow in the School of Biological Sciences, added: "This reduced ability to land on the zebra’s coat may be due to stripes disrupting the visual system of the horse flies during their final moments of approach.

"Stripes may dazzle flies in some way once they are close enough to see them with their low-resolution eyes."

(C) T Caro et al. PlosONE

Their second experiment was to observe horse fly behaviour around the same horses wearing different coloured cloth coats: black, white or zebra striped livery. This excluded any differences in behaviour or smell between horses and zebras. Just as before, when horses wore coats with striped patterns, they experienced fewer horse fly landings compared to when they wore single-colour coats.

Horse flies are a widespread problem for domestic animals so mitigating techniques, such as the development of anti-fly wear designed to resemble zebra stripes, may, from this research, be an interesting outcome for animal health and wellbeing.

The research also observed zebra and horse behaviour in response to biting flies. Zebras exhibited preventative behaviour, such as running away and tail swishing at a far higher rate than horses. Consequently, any horse flies that did successfully land on zebras spent less time there compared to those landing on horses, with few staying long enough to probe for a blood meal.

In Africa where zebras are native, horse flies carry dangerous debilitating diseases such as trypanosomiasis and African horse sickness which cause wasting and often death. Therefore, it is unsurprising that zebras utilise both behavioural defences and morphological striping to avoid horse flies.

This research provides new evidence for the theory that zebras evolved dichromatic striped coats to evade biting flies and has considerable implications for the horse industry.

For more details see:

Benefits of zebra stripes: Behaviour of tabanid flies around zebras and horses

T. Caro, Y. Argueta, E.S. Briolat, J. Bruggink, M. Kasprowsky, J. Lake, M.J. Mitchell, S. Richardson, M. How.

PLoS ONE 14(2): e0210831

https://doi.org/10.1371/journal.pone.0210831