Researchers identified an adverse reaction in the fetlock joint of horses after giving them a second dose of mesenchymal stem cells from a donor.
By contrast, no such reaction was found in horses receiving a second injection of the bone marrow-derived stem cells sourced from their own bodies, provided they had gone through a laboratory decontamination process first.
Texas A&M University researchers have reported their findings, based on a study using 18 Quarter horses, in the journal Stem Cell Research & Therapy.
The injection of mesenchymal stem cells into joints affected by osteoarthritis has been shown to be an effective therapy.
However, Ashlee Watts and her colleagues noted that no direct comparison had been made of the response of the synovial joint to the injection of stem cells derived from the patient’s own body as opposed to a donor.
The study team set out to assess the clinical response of each treatment, using stem cells prepared in a way that minimized protein contamination arising from laboratory techniques that used bovine serum as food for the cells in their preparation.
The horses were divided into groups, with some receiving their own stem cells in a fetlock, some receiving donor cells from another animal in a fetlock, and some horses also received their own stem cells, but without having them processed to remove protein contaminants from the fetal bovine serum used in their preparation.
The injections were repeated after four weeks.
In the week following each injection, the horses were clinically assessed and joint fluid was removed from the treated joints for evaluation.
The researchers reported that, following the first injection, there were no differences in clinical parameters over time.
However, following the second round of joint injections, there was a significant adverse response in the joints that received the donor-derived stem cells, with a trend toward increased lameness and significantly increased inflammation.
The horses that received a second injection of their own stem cells without the laboratory technique for bovine protein decontamination also had an adverse response, with evidence of pain and significantly increased inflammation.
By contrast, the horses that received the second injection of their own cells that had been through protein decontamination showed no negative reaction.
The researchers said the laboratory technique for cell preparation to remove the protein contaminants arising from the fetal bovine serum had a profound effect on the horse’s adverse response.
The laboratory method they used to deplete cells of the bovine proteins resulted in a greater than 95% reduction in the amount of this contaminant, with a corresponding reduction in adverse inflammatory reaction in cases where the stem cells had been derived from the horse’s own body.
Using this laboratory technique to minimize bovine protein contamination, in strong contrast to previous reports, a single injection of stem cells sourced from the horse’s own body did not result in an adverse clinical reaction.
They concluded that repeated injections of donor-derived stem cells resulted in an adverse clinical response, suggesting there was immune recognition of these cells sourced from another horse.
The study team comprised Watts, Amanda-Jo Joswig, Alexis Mitchell, Kevin Cummings, Gwendolyn Levine, Carl Gregory and Roger Smith III.
Repeated intra-articular injection of allogeneic mesenchymal stem cells causes an adverse response compared to autologous cells in the equine model
Amanda-Jo Joswig, Alexis Mitchell, Kevin J. Cummings, Gwendolyn J. Levine, Carl A. Gregory, Roger Smith III and Ashlee E. Watts.
Stem Cell Research & Therapy 2017 8:42 DOI: 10.1186/s13287-017-0503-8