Final Report Summary - HORAB (Source and efficacy of human olfactory ensheathing cells in the repair of brachial plexus avulsion.)
We have studied the positive effects of a cell called the olfactory ensheathing cell which can be transplanted into the central nervous system (CNS) to stimulate nerve repair. This is a potential candidate therapy for patients with spinal nerve root injuries, which often happens after motorcycle injuries.
The mammalian adult central nervous system is unable to regenerate after injury. There is presently no effective cure, apart from supportive measures and physiotherapy, because the CNS environment is hostile to the injured nerve fibres and does not allow them to regenerate effectively. However, in the adult CNS, the sense of smell is unique in that it is the only part of the nervous system which regenerates continually throughout adult life. In humans, this allows the maintenance of the sense of smell, despite a continuous chemical insult to the olfactory neurons from the environment, and is due to the presence of the olfactory ensheathing cell. This unique cell provides the natural pathway for growth of olfactory nerve fibres into the brain, and provides supportive cues and growth factors to help the regenerating fibres. We are investigating the potential to obtain OECs from the noses of patients, culture the cells in the laboratory, and transplant them to the site of nerve root injury at the time of surgical repair. Since these cells encourage regeneration of neurons in the nose we propose that these cells may have a similar reparative effect if transplanted elsewhere in the nervous system, which has been demonstrated in animal studies already.
The first stage of this research is to learn how to obtain OECs from patients. To do this, we have taken samples of tissue from inside the nose of patients who are undergoing routine surgery to the nose, and purifying and growing the cells in the laboratory. We have discovered the best region within the nose from which to take the sample, and demonstrated patient safety by assessing their sense of smell before and after biopsy, and asking patients to complete a quality of life questionnaire. The yield of the cells is variable, and is greater in patients of younger age, and in patients with less disease of the nasal mucosa (such as infection or allergic inflammation). We have obtained good yields of OECs from several samples, but is subject to variations in patients, sample quality, and surgical technique also. To prepare for human application, we have built a state-of-the-art clean culture room, in which OECs can be grown to pharmaceutical standards of cleanliness and quality control.
We have determined clinical methods which will be used to assess outcome in this group of patients, including Magnetic Resonance Imaging (MRI) spectroscopy of spinal cord after injury of the brachial plexus (nerve roots to the arms), electrophysiological and clinical examination. This has been studied in a group of 26 patients with brachial plexus injury, to determine baseline characteristics against which future transplant patients can be compared.
Simultaneously, we have developed an in vivo experimental model of brachial plexus avulsion, and are able to study this model histologically, and also a laboratory model using spinal cord slice cultures as an in vitro assay to study the behaviour of candidate reparative cells more quickly, in a dish.
The mammalian adult central nervous system is unable to regenerate after injury. There is presently no effective cure, apart from supportive measures and physiotherapy, because the CNS environment is hostile to the injured nerve fibres and does not allow them to regenerate effectively. However, in the adult CNS, the sense of smell is unique in that it is the only part of the nervous system which regenerates continually throughout adult life. In humans, this allows the maintenance of the sense of smell, despite a continuous chemical insult to the olfactory neurons from the environment, and is due to the presence of the olfactory ensheathing cell. This unique cell provides the natural pathway for growth of olfactory nerve fibres into the brain, and provides supportive cues and growth factors to help the regenerating fibres. We are investigating the potential to obtain OECs from the noses of patients, culture the cells in the laboratory, and transplant them to the site of nerve root injury at the time of surgical repair. Since these cells encourage regeneration of neurons in the nose we propose that these cells may have a similar reparative effect if transplanted elsewhere in the nervous system, which has been demonstrated in animal studies already.
The first stage of this research is to learn how to obtain OECs from patients. To do this, we have taken samples of tissue from inside the nose of patients who are undergoing routine surgery to the nose, and purifying and growing the cells in the laboratory. We have discovered the best region within the nose from which to take the sample, and demonstrated patient safety by assessing their sense of smell before and after biopsy, and asking patients to complete a quality of life questionnaire. The yield of the cells is variable, and is greater in patients of younger age, and in patients with less disease of the nasal mucosa (such as infection or allergic inflammation). We have obtained good yields of OECs from several samples, but is subject to variations in patients, sample quality, and surgical technique also. To prepare for human application, we have built a state-of-the-art clean culture room, in which OECs can be grown to pharmaceutical standards of cleanliness and quality control.
We have determined clinical methods which will be used to assess outcome in this group of patients, including Magnetic Resonance Imaging (MRI) spectroscopy of spinal cord after injury of the brachial plexus (nerve roots to the arms), electrophysiological and clinical examination. This has been studied in a group of 26 patients with brachial plexus injury, to determine baseline characteristics against which future transplant patients can be compared.
Simultaneously, we have developed an in vivo experimental model of brachial plexus avulsion, and are able to study this model histologically, and also a laboratory model using spinal cord slice cultures as an in vitro assay to study the behaviour of candidate reparative cells more quickly, in a dish.