Autologous Unpurified Adipose Tissue Enhances Peripheral Nerve Regeneration Through Long (30 + 40 mm) Autografts
Brian P. Cleary, BSc., Carrie A. Kubiak, M.D., Scott W. Sabbagh, BSc., Vincent Thieu, BSc., Paul S. Cederna, M.D., Stephen W. Kemp, Ph.D.
University of Michigan, Ann Arbor, MI, USA.
PURPOSE: Approximately 360,000 Americans suffer from upper extremity paralytic syndromes annually, leading to 8.6 million missed work days. The gold standard for peripheral nerve gap repair is autologous nerve grafting. Unfortunately, this approach yields suboptimal functional outcomes, often resulting in motor and sensory deficits and overall impaired quality of life. Adipose-derived stem cells (ASCs) have been previously shown to enhance peripheral nerve regeneration. However, ASC processing leads to both clinical and regulatory burdens. Unpurified fat is whole adipose tissue that is harvested without subsequent ASC isolation. In addition, harvesting of unpurified adipose tissue is currently approved by the FDA. The purpose of the present study was to investigate the effect of unpurified adipose tissue on nerve regeneration through long (30 + 40 mm) autografts in the rat.
METHODS: F344 rats were used in this study and were randomly assigned to one of four experimental groups: (1) 30 mm autograft; (2) 30 mm autograft + unpurified adipose tissue; (3) 40 mm autograf;t, and (4) 40 mm autograft + unpurified adipose tissue. All animals were tested at baseline, and were then followed serially for 12 weeks. Outcome measures included sensorimotor (ladder rung, walking track), and sensory pain assessments (von Frey). Terminal outcome muscle measures examined EMG (compound muscle action potentials, nerve conduction velocity) and muscle force parameters (twitch and tetanic forces).
RESULTS: Animals in both the 30 and 40 mm autograft + unpurified fat group displayed enhanced peripheral regeneration compared to the non-fat administered autograft groups. Specifically, these animals displayed increased EMG and muscle force parameters at study endpoint. Sensorimotor assessments were enhanced in these animals, and histomorphometrical assessment showed differences between autograft and autograft + unpurified fat groups.
CONCLUSION: Unpurified fat enhanced peripheral nerve regeneration through long autografts. Harvesting of unpurified fat circumvents current FDA regulatory burdens, is easily obtainable, and has the potential to change current clinical management of traumatic peripheral nerve injuries. More specifically, this research can potentially lay the groundwork to change clinical practice of nerve injury.
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