Grants Funded

Abstract
Project Summary: Despite the advancement of microsurgical techniques, complete recovery of sensory and motor functions is rarely attainable. Sub-optimal results are especially noticeable for delayed, or proximal nerve injury repairs, which require regenerating nerves to travel longer distances to reach their target organs. In these circumstances, denervated Schwann cells (SC) gradually undergo senescence and atrophy, resulting in reduced secretion of neurotrophic factors and disruption of bands of Bungner. Adipose-derived stem cells (ASC) may potentially enhance nerve regeneration due to their ease of harvest, ability to secrete neurotrophic factors, and differentiate into SCs phenotypes. However, clinical utilization of purified or manipulated ASCs is highly restricted by the FDA. A work-around this constraint is the employment of autologous unpurified fat grafts, whose native ASCs may benefit nerve regeneration without regulatory burdens. The long-term goal of this research is to improve nerve regeneration and functional outcomes in delayed nerve repair and proximal nerve injuries. Our overall objective is to supplement regenerating axons and senescent SCs with multipotent stem cells naturally found in autologous unpurified fat, whose harvest and use is translatable to current clinical settings. The central hypothesis is that ASCs contained in lipoaspirate can differentiate into SCs phenotypes, and provide structural and trophic support for growing, regenerating nerves. By using autologous unpurified adipose tissue, any potential regulatory and scaling issues can be avoided. Persuaded by strong preliminary animal data in our laboratory, this hypothesis will be tested by the following specific aims: 1) Use of unpurified fat grafts to enhance nerve regeneration in both chronic denervation and chronic axotomy rat models, and, 2) Bridging a nerve gap with nerve autografts augmented with autologous unpurified fat to improve regeneration and functional outcomes. In Specific Aim 1, unpurified autologous fat grafts will separately determine SCs or motorneuron function. In Specific Aim 2, the use of unpurified fat grafts will be assessed for a surgically relevant delayed nerve repair procedure. This study is innovative since it departs from the status quo by proposing a novel, yet accessible intervention to address a clinical challenge; it is significant because the results are expected to advance current surgical standards for proximal nerve injury or delayed repair. Impact Statement: Despite the innate capacity of injured peripheral nerves to regenerate, functional recovery is dismal after delayed repair or when proximal nerve trunks are injured. Adipose-derived stem cells (ASC) may potentially enhance nerve regeneration due to their ease of harvest, ability to secrete neurotrophic factors, and differentiate into Schwann cells phenotypes. However, clinical utilization of purified ASC is highly restricted by the FDA. This constraint may be avoided by employment of autologous unpurified fat grafts, whose native ASCs may benefit nerve regeneration. The proposed study is easily translatable to the clinical setting, requires no FDA approval, and could lead to enhanced functional recovery, increased quality of life, and decreased burdens for patients with nerve injuries.

Biography
Stephen Kemp, PhD completed his Honours Bachelor of Science at the University of Toronto, where he conducted his undergraduate thesis under the supervision of Dr. Gerald Cupchik. During this time, Dr. Kemp’s research focused on the psychology of creativity, and the development of a "matching and modulation" psychological model of aesthetic response. Dr. Kemp’s undergraduate thesis led to the publication of two peer-reviewed publications, and one book chapter. Following graduation, Dr. Kemp completed his Master’s degree at Wilfrid Laurier University in Waterloo, under the supervision of Linda Parker, PhD. His research focused on the effect of delta-9-tetrahydrocannabinol (THC) on lithium induced sickness behaviours in both rats and house musk shrews. Stephen completed his PhD at the University of Calgary, under the mentorship of Rajiv Midha, MD, focusing on the anatomical, sensorimotor, and functional evaluation of peripheral nerve regeneration through bio-engineered conduits in rodents. During this tenure, Dr. Kemp became a member of numerous scientific societies, including the Society for Neuroscience, the Canadian Society for Neuroscience, and the American Society for Peripheral Nerve. Dr. Kemp also published nine peer-reviewed publications. One of his papers was highlighted in Experimental Neurology as an outstanding paper. Following his tenure in Calgary, Dr. Kemp accepted a postdoctoral fellowship at the University of Toronto and The Hospital for Sick Children with Gregory Borschel, MD and Tessa Gordon, PhD. Dr. Kemp continues to investigate treatment of nerve injuries, and has expanded his research to focus on treatment of neonatal nerve injuries. Dr. Kemp has won numerous awards during his scientific career, including prestigious postdoctoral awards. Overall, Dr. Kemp has 14 published peer reviewed publications, two book chapters, two News and Views commentaries, 18 abstracts, and 21 international conference presentations.