Can stem cells speed up wound healing?
Fences, trailers, ropes, farm equipment, sticks, other horses – the causes of traumatic wounds on horses creates a staggering list.
By Charlotte Corbett
And even with early detection and dedicated treatment, equine wounds heal slowly, have complications and can heal with ugly scars.
The formation of granulation tissue in a wound is normal and important for repair. However, when this tissue is excessive in amount, it's called "proud flesh," explains Dr. Spencer Barber, an equine surgeon and professor at the Western College of Veterinary Medicine (WCVM).
Proud flesh can occasionally lead to decreased mobility, but more commonly, Barber says it results in unsightly scars and increased healing times that are costly for an owner. It may also affect a horse's suitability for a particular career and its potential sale value.
A team of WCVM researchers, led by Barber (the principal investigator) and his graduate student Dr. Suzanne Mund, hope to change that reality through research focused on understanding the effects of stem cells on the molecules that direct the healing process. Other members of the team are Drs. Ali Honaramooz, Bruce Wobeser, Daniel MacPhee and John Campbell.
Barber says stem cells may assist wound healing in a number of ways:
Barber and his research team will evaluate the changes to the inflammatory response in the skin wounds and the differentiation of stem cells into cells of repair. The team is using stem cells purchased from a commercial company that harvested them from the umbilical cord of a newborn foal and then grew the stem cells in the laboratory.
The team's first project was to determine whether stem cells administered intravenously (IV) migrate to horses' wounds. The WCVM researchers used the IV method to administer a large dose of stem cells, which were labelled with a fluorescent dye, to two horses with surgically-created skin wounds. Then, at predetermined intervals, they collected wound biopsies and looked for the labelled stem cells within the tissue. Based on their findings, they were able to prove that the stem cells selectively migrate to the area of injury.
"It's cutting edge research," says Barber. "No one else has given this many cells intravenously to horses before or proved that they migrate to the wounds. It's very exciting."
Barber says the team is now conducting a second experiment that will focus on looking at the immunomodulatory aspects as well as the differentiation of the stem cells into cells of repair after they're administered intravenously. The researchers have collected all of the samples and are now in the process of analyzing them.
A portion of this study is determining the role of numerous cytokines in the wounded tissue. Cytokines are proteins that dictate cell-to-cell communication and modulate the immune response. Various cells within the tissue and surrounding blood vessels release cytokines, and their quantity and effectiveness partially dictate the processes of the inflammatory reaction and the wound healing.
One of the ways that cytokines modulate the immune response is by encouraging white blood cells such as neutrophils to travel from the bloodstream into the damaged tissue. In previous research, scientists studying other species have confirmed that CXCL8 and CXCL10, two of the cytokines under investigation, initiate neutrophil migration and help "killer" T cells to consume pathogens such as bacteria.
These two chemokines are of particular interest since CXCL8 is an acute inflammatory molecule and CXCL10 is a chronic phase molecule. In the future, the researchers hope that veterinarians will be able to tweak these two cytokines and duplicate the wound response that's found in ponies.
Although horses and ponies look nearly identical, they heal differently. Ponies have a marked by short-lived inflammatory response and their wounds don't produce proud flesh. Their wounds also heal more quickly than horses. Horses have a longer healing process and lower levels of inflammation — especially in leg wounds versus body wounds — that never reach the high peaks found in ponies.
The differences in healing between horses and ponies is likely due to cellular differences in their healing response and inflammatory reaction — possibly differences in CXCL8 and CXCL10. Barber's research team is also investigating beta-arrestin 2, a protein that can negatively regulate neutrophil activation and inhibit the production of cytokines, and it may be useful for controlling overstimulation from the other cytokines. Preliminary results appear to support a correlation of beta-arrestin 2 with wound healing.
The WCVM researchers are taking an important first step toward using stem cells as a therapy for wounded horses. To Barber's knowledge, no other research team has administered a large dosage of stem cells intravenously to horses, proven the migration of the stem cells to wounds and identified proteins CXCL8, CXCL10 and beta-arrestin 2 in equine skin wounds.
"Hopefully analysis of the latest biopsies will reveal more information regarding the healing process," says Barber. "Once we understand the role stem cells play in modulating the inflammatory response and their ability — or limitations — to differentiate into cells of repair, we can utilize them to enhance the speed and quality of the repair."
This research project has received financial support from the Mark and Pat DuMont Equine Orthopedics Research Fund and the Townsend Equine Health Research Fund.
Charlotte Corbett of Bruno, Sask., is a second-year veterinary student who was part of the WCVM's Undergraduate Summer Research and Leadership program in 2016. Charlotte's story is part of a series of stories written by WCVM summer research students.
The formation of granulation tissue in a wound is normal and important for repair. However, when this tissue is excessive in amount, it's called "proud flesh," explains Dr. Spencer Barber, an equine surgeon and professor at the Western College of Veterinary Medicine (WCVM).
Proud flesh can occasionally lead to decreased mobility, but more commonly, Barber says it results in unsightly scars and increased healing times that are costly for an owner. It may also affect a horse's suitability for a particular career and its potential sale value.
A team of WCVM researchers, led by Barber (the principal investigator) and his graduate student Dr. Suzanne Mund, hope to change that reality through research focused on understanding the effects of stem cells on the molecules that direct the healing process. Other members of the team are Drs. Ali Honaramooz, Bruce Wobeser, Daniel MacPhee and John Campbell.
Barber says stem cells may assist wound healing in a number of ways:
- The healing response in horses has been linked to the inflammatory reaction. Since stem cells have an immunmodulating effect and produce numerous proteins, they may affect the healing speed and the quality of wound repair.
- Stem cells are capable of replicating into cells of repair — such a myofibroblasts and epithelial cells — that could enhance not only the speed but also the quality of repair.
Barber and his research team will evaluate the changes to the inflammatory response in the skin wounds and the differentiation of stem cells into cells of repair. The team is using stem cells purchased from a commercial company that harvested them from the umbilical cord of a newborn foal and then grew the stem cells in the laboratory.
The team's first project was to determine whether stem cells administered intravenously (IV) migrate to horses' wounds. The WCVM researchers used the IV method to administer a large dose of stem cells, which were labelled with a fluorescent dye, to two horses with surgically-created skin wounds. Then, at predetermined intervals, they collected wound biopsies and looked for the labelled stem cells within the tissue. Based on their findings, they were able to prove that the stem cells selectively migrate to the area of injury.
"It's cutting edge research," says Barber. "No one else has given this many cells intravenously to horses before or proved that they migrate to the wounds. It's very exciting."
Barber says the team is now conducting a second experiment that will focus on looking at the immunomodulatory aspects as well as the differentiation of the stem cells into cells of repair after they're administered intravenously. The researchers have collected all of the samples and are now in the process of analyzing them.
A portion of this study is determining the role of numerous cytokines in the wounded tissue. Cytokines are proteins that dictate cell-to-cell communication and modulate the immune response. Various cells within the tissue and surrounding blood vessels release cytokines, and their quantity and effectiveness partially dictate the processes of the inflammatory reaction and the wound healing.
One of the ways that cytokines modulate the immune response is by encouraging white blood cells such as neutrophils to travel from the bloodstream into the damaged tissue. In previous research, scientists studying other species have confirmed that CXCL8 and CXCL10, two of the cytokines under investigation, initiate neutrophil migration and help "killer" T cells to consume pathogens such as bacteria.
These two chemokines are of particular interest since CXCL8 is an acute inflammatory molecule and CXCL10 is a chronic phase molecule. In the future, the researchers hope that veterinarians will be able to tweak these two cytokines and duplicate the wound response that's found in ponies.
Although horses and ponies look nearly identical, they heal differently. Ponies have a marked by short-lived inflammatory response and their wounds don't produce proud flesh. Their wounds also heal more quickly than horses. Horses have a longer healing process and lower levels of inflammation — especially in leg wounds versus body wounds — that never reach the high peaks found in ponies.
The differences in healing between horses and ponies is likely due to cellular differences in their healing response and inflammatory reaction — possibly differences in CXCL8 and CXCL10. Barber's research team is also investigating beta-arrestin 2, a protein that can negatively regulate neutrophil activation and inhibit the production of cytokines, and it may be useful for controlling overstimulation from the other cytokines. Preliminary results appear to support a correlation of beta-arrestin 2 with wound healing.
The WCVM researchers are taking an important first step toward using stem cells as a therapy for wounded horses. To Barber's knowledge, no other research team has administered a large dosage of stem cells intravenously to horses, proven the migration of the stem cells to wounds and identified proteins CXCL8, CXCL10 and beta-arrestin 2 in equine skin wounds.
"Hopefully analysis of the latest biopsies will reveal more information regarding the healing process," says Barber. "Once we understand the role stem cells play in modulating the inflammatory response and their ability — or limitations — to differentiate into cells of repair, we can utilize them to enhance the speed and quality of the repair."
This research project has received financial support from the Mark and Pat DuMont Equine Orthopedics Research Fund and the Townsend Equine Health Research Fund.
Charlotte Corbett of Bruno, Sask., is a second-year veterinary student who was part of the WCVM's Undergraduate Summer Research and Leadership program in 2016. Charlotte's story is part of a series of stories written by WCVM summer research students.