Cell Therapy Improves Tendon Regeneration in Sheep

Researchers here move from rodents to sheep in testing the ability of a comparatively simple autologous cell therapy to improve regeneration following tendon injury. The results appear much the same in both species, which suggests that human trials will produce positive results. This approach will join a few other cell therapies aimed at tendon repair and tested in human trials over the past twenty years. The field moves slowly, like much of medicine.

In the search for new and better ways to heal injured tendons, the medical world is looking closely at regenerative therapies. In particular, autologous adipose micrografts (AAMGs) and stromal vascular fraction (SVF) are showing promise. SVF, derived from adipose tissue, contains heterogeneous cell populations including stem cells and immune cells involved in regeneration. In a previous study on rats, AAMGs and SVF improved tendon healing in 60 percent to 70 percent of treated animals. The purpose of a new study was to evaluate the effects of AAMG in sheep with tendinopathy, as larger animals are more comparable to humans than are rodents.

This is also the first study on an animal model employing a mechanical fat breakdown system as an alternative to enzymatic digestion to isolate the SVF. This procedure is able to maintain the microenvironment of the perivascular niche, while at the same time removing any pro-inflammatory factors. The residual SVF contain pericytes that are able to gradually convert into activated adipose stem cells.

The team carried out the study by inducing tendinopathy in both common calcaneal tendons (CCT) of 16 female sheep. Tendinopathy is a breakdown of collagen in a tendon, resulting in burning pain, reduced flexibility and limited range of motion. Four animals were assigned to a non-treated group as a control. Each of the other 12 sheep had one CCT injected with AAMG, while its contralateral CCT was left untreated. At 8 weeks after treatment, the treated group showed a final tendon diameter (9.1 ± 1.4 mm) and a hardness expression (62%) that were similar to the original healthy tendon (8.1 ± 1.1 mm; 100%), with a significant recovery compared with the control group (9.5 ± 1.7 mm; 39%). Moreover, histological analysis of the treated group revealed an improvement in the fiber orientation score, fiber edema score, infiltrative-inflammatory process, and necrosis score compared with control group.

Link: https://www.eurekalert.org/news-releases/925276


I'm a neuroscientist. I had a tendinopathy in a rotator cuff tendon (diagnosed by MRI). After nine months of anti-inflammatories, physical therapy and cortisone shots, my orthopedic surgeon said there was nothing else he could do. There was no tear to repair, the chronic inflammation was likely age-related (I was 61), and tendons are hard to heal. Also I couldn't have any more cortisone. After doing some research on sterile inflammation, damage-induced senescence and collagen synthesis, I developed my own protocol.
I took 25 mg/kg/day of fisetin for 4 days to kill senescent cells. I used more fisetin for a longer period than the Mayo protocol because tendons have a poor blood supply and I wanted at least a little fisetin to get to the tendons. I waited two days for the senescent cells to die and start getting cleared away and then I started taking daily everything my body can use to make collagen: collagen peptides, AKG, vitamin C, plus curcumin to suppress residual inflammation and glucosamine (although evidence of its effectiveness is limited).
All signs of the tendinopathy disappeared in less than three weeks. In two weeks more I had my range of motion back. Although I understood the theory, I was surprised how well and how fast it worked.

Posted by: Vince at August 27th, 2021 1:58 PM
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