Collection and Characterisation of Human Olfactory Ensheathing Cells
- Conditions
- Spinal Cord Injury
- Interventions
- Procedure: OB Retrieval During Anterior Cranial SurgeryProcedure: Frontal Craniotomy and retrieval of OBs
- Registration Number
- NCT02870426
- Lead Sponsor
- St George's, University of London
- Brief Summary
We aim to retrieve olfactory bulbs (OBs) from suitable human donors. We have defined two groups who will qualify:
Group 1 - Deceased Donors:
1A: Donors after brainstem death (DBDs) undergoing solid organ donation
1B: Donors after brainstem death (DBDs) considered unsuitable for solid organ donation
Group 2 - Living Donors:
Neurosurgical patients undergoing anterior cranial surgery in which the olfactory nerve (ON) is cut as part of the surgical procedure. The OB of the concomitant severed ON would be donated.
We aim to optimise OB collection and Olfactory Ensheathing Cell (OEC) culture and storage. We will study the effects of patient diagnosis, age, cause of death (if applicable), co-morbidities and warm ischaemic time on cell survival and regenerative function.
In future studies we aim to store OECs in a GMP facility and transplant OECs into patients with spinal cord injuries.
- Detailed Description
Spinal cord injury (SCI) is a devastating condition. To date there is no treatment to improve outcome. There is limited regenerative capacity of the central nervous system (CNS), such that damaged neurons and severed axons are not replaced.
A substantial body of evidence suggests that olfactory ensheathing cells (OECs) obtained from olfactory bulbs (OBs) facilitate neuronal regeneration in rodents and humans with SCI. Indeed, transplanting autologous OECs from an OB into the injury site improved neurological outcome in a patient with SCI.
Harvesting autologous OBs to culture OECs has several disadvantages:
1. If the OECs do not grow in vitro, the transplantation is abandoned;
2. The retrieval procedure exposes a paralysed patient to the risks of craniotomy;
3. Excising an OB can impair the sense of smell; and
4. The number of OECs obtained is limited to one OB.
Investigators will collect human OECs from suitable donors which we have defined as two groups. Group 1 patients will be brain dead donors identified by the neuro-intensive care team as potential candidates for solid organ donation. The OBs will be retrieved as near to death as possible. Group 2 patients will be living donors undergoing elective neurosurgery in which the olfactory nerve is sacrificed as part of that procedure.
There are two OBs located at the anterior skull base, responsible for transmitting the sensation of smell from the nose to the brain. Obtaining OECs requires a craniotomy (opening the skull) to remove the OBs.
PHASE 1 will be divided into 2 stages. In stage 1 we will culture OECs and characterise them in the central laboratory. We aim to determine how the yield of OECs and their regenerative properties are affected by freeze-thaw, time left at room temperature and time left at 40C before culture as well as patient age. Each harvested sample will be transferred to the lab for further processing. Processing includes but is not limited to histological fixation, sectioning and staining, cell culture and storage. Some OECs will be frozen in liquid nitrogen to determine whether they can indeed be stored. In stage 2 we will transfer OECs outside St. George's to a GMP facility (to be determined). In the GMP facility, the OECs will be processed and stored according to the optimised conditions we have determined.
In PHASE 2, the OECs will be transplanted into patients with SCI.
Recruitment & Eligibility
- Status
- UNKNOWN
- Sex
- All
- Target Recruitment
- 50
Not provided
Not provided
Study & Design
- Study Type
- OBSERVATIONAL
- Study Design
- Not specified
- Arm && Interventions
Group Intervention Description Group 2: OB Retrieval During Anterior Cranial Surgery Neurosurgical patients undergoing anterior cranial surgery in which the olfactory nerve (ON) is cut as part of the surgical procedure. The OB of the concomitant severed ON would be donated. Group 1B: Frontal Craniotomy and retrieval of OBs Donors after brainstem death (DBDs) considered unsuitable for solid organ donation Group 1A: Frontal Craniotomy and retrieval of OBs Donors after brainstem death (DBDs) undergoing solid organ donation
- Primary Outcome Measures
Name Time Method Ability to culture olfactory ensheathing cells from human donors 10-15 days Number of olfactory ensheathing cells cultured per olfactory bulb at days 10-15 in vitro.
- Secondary Outcome Measures
Name Time Method Effect of cause of death for Group 1 donors 10-15 days Plot of cause of death vs. Number of olfactory ensheathing cells cultured per olfactory bulb at days 10-15 in vitro.
Effect of freeze/thaw cycles 10-15 days Plot of number of freeze/thaw cycles vs. Number of olfactory ensheathing cells cultured at days 10-15 in vitro.
Effect of time from extraction to culture at 4 deg C 1 month Plot of time from extraction to culture at 4 deg C vs. Number of olfactory ensheathing cells cultured.
Effect of patient age 10-15 days Plot of patient age vs. Number of olfactory ensheathing cells cultured per olfactory bulb at days 10-15 in vitro.
Effect of storage in liquid nitrogen up to 1 month Plot of Number of olfactory ensheathing cells cultured at days 10-15 in vitro when cells are cultured fresh vs. after one week and one month storage in liquid nitrogen.
Effect of time from extraction to culture at room temperature 1 month Plot of time from extraction to culture vs. Number of olfactory ensheathing cells cultured.
Trial Locations
- Locations (1)
St George's Hospital
🇬🇧London, Tooting, United Kingdom