Johnny Huard, PhD, Honored with Kappa Delta Ann Doner Vaughan Award

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Johnny Huard, PhD

According to Johnny Huard, PhD, distinguished professor and vice chair for research in the department of orthopaedic surgery at the University of Texas Health Science Center at Houston (UTHealth), “The clinical translation of muscle stem cell technology for orthopaedic applications, such as repair of skeletal muscle, peripheral nerve, bone, and a variety of intra-articular tissues (meniscus, ligament and articular cartilage), is poised to become a reality in the near future.”  

In 2004, Dr. Huard won the Kappa Delta Young Investigator award for his discovery of muscle-derived stem cells (MDSCs) and their characterization. At the 2018 AAOS Annual Meeting, Dr. Huard, who also is the director of the Center for Regenerative Sports Medicine and the chief scientific officer at the Steadman Philippon Research Institute in Vail, Colo., will be honored with the Kappa Delta Ann Doner Vaughan award for his subsequent efforts to develop a regenerative medicine approach, based on the use of these autologous adult stem cells, to improve healing of numerous tissue types. Ongoing clinical trials using MDSCs to treat stress urinary incontinence and myocardial infarction may facilitate clinical translation of the muscle stem cell technology for orthopaedic applications.

Encouraging angiogenesis

Dr. Huard’s research has found that MDSCs appear to share similarities with other stem cell types derived from blood vessel walls, suggesting that this might be their source as well (Fig. 1). This conclusion has fostered subsequent research to develop noninvasive approaches to improve angiogenesis, which he believes will increase the number of blood vessel-derived stem cells and improve tissue repair.

One series of experiments, using a mouse model, tested whether transplanting MDSCs into injured skeletal muscle would lead to improved muscle healing after injury by promoting angiogenesis and decreasing fibrosis. “Our results suggest that transplantation of MDSCs improves skeletal muscle repair of dystrophic mice by modulating angiogenesis, consequently improving muscle regeneration and reducing fibrosis in dystrophic mdx mice,” he wrote.

He further found that using anti-fibrotic agents along with MDSC transplantation (a combined approach) resulted in better skeletal muscle healing than using either treatment individually. In addition, other rehabilitation approaches—including exercise, neuromuscular electrical stimulation, and massage—may also enhance angiogenesis and improve muscle healing. This would enable people to remain active longer, thus reducing the risk of conditions such as cardiovascular disease, obesity, and osteoporosis, which are associated with inactivity.

Implications for healing—and aging

“Although skeletal muscle injuries account for 30 percent to 50 percent of sports-related injuries, and half of all occupational injuries in the United States,” said Dr. Huard, “treatment is currently unsatisfactory, with injured tissues healing or regenerating slowly and often developing scar tissue, resulting in incomplete functional recovery.” His findings on the role of angiogenesis in healing led him to conduct a series of studies examining their implications for improving healing, not only in skeletal muscle but also in nonmuscle tissues such as after anterior cruciate ligament (ACL) repair.

Injuries to the medial collateral ligament, which is highly vascularized, typically heal more effectively than those to the poorly vascularized ACL. Similarly, a potentially richer supply of vascular-derived stem cells in the vascular region could account for differences in healing between the inner (avascular) and peripheral (vascular) parts of the meniscus.

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Fig. 1
Courtesy of Johnny Huard, PhD

Dr. Huard was able to demonstrate the presence of blood vessel-derived stem cells within the ACL (septum), and more importantly, their potential use to improve ACL reconstruction (ACLR) outcomes via intra-articular injection of blood vessel-derived stem cells. He also found that stem cell delivery via a stem cell sheet wrapped around the tendon graft further enhanced the beneficial effects of stem cells on ACLR outcomes. Recent laboratory studies on human menisci showed the potential for regenerative strategies using blood vessel stem cells found in the vascularized region of the meniscus.

Vascularity and angiogenesis may also play important roles in the depletion of stem cells due to aging and disease. “Identifying strategies to prevent the progressive loss of tissue homeostasis and functional reserve associated with aging is essential for maintaining the health of our aging population,” wrote Dr. Huard. To this end, his recent research has focused on the interrelationship between angiogenesis and adult stem cell depletion during normal and accelerated aging.

Other studies, he noted, have identified rejuvenating factors capable of rescuing defective old adult stem cells and improving tissue regeneration. Research has shown that host cells are the greatest contributors to the repair process and that implanted cells attract host cells to the injury site. These studies support the use of autologous MDSCs to mediate bone regeneration.

A recent study reported significant improvements in both lifespan and health when MDSCs isolated from young wild-type mice were transplanted into progeroid mice. Although the mechanism by which this occurs is still unclear, a combination of several factors may be involved. Dr. Huard is currently testing these factors to determine whether they can delay natural and accelerated aging.

In particular, he is investigating the impact of pregnancy on healing, using a mouse model. “We posit [the induction of pregnancy] will improve musculoskeletal tissue healing by rescuing maternal stem cells from depletion during aging. … Preliminary results indicate improvements in skeletal muscle and bone healing in pregnant mice compared to age-matched, non-pregnant mice,” he wrote. “Future investigation will determine whether we can rejuvenate aged and diseased micro-environments in aged animals through the induction of pregnancy, and whether this could improve the degenerative changes associated with diseased and aged tissues through the rescue of their stem cells from depletion.”

In conclusion, he noted, “The role of pregnancy in the rejuvenation of tissues may have profound implications for human health and aging, including an increased understanding of why women exhibit superior longevity compared to men, and knowledge that may influence tissue engineering and regenerative medicine in the future.”

Huard to accept award and present later in the week

Dr. Huard will receive the award during the Your Academy 2018 event on Thursday. He will present his award-winning paper, “Adult Stem Cells, Blood Vessels, and Angiogenesis: Major Determinants for Musculoskeletal Tissue Repair After Injury, Disease, and Aging,” on Sunday, March 11, at the Hyatt Regency New Orleans as part of the 2018 Annual Meeting of the Orthopaedic Research Society.

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