1) Dr. Carlos Lima (Portugal)

2) Dr. Hongyun Huang (China)

3) Dr. Alan MacKay-Sim (Australia)

4) Dr. Tiansheng Sun (China)

5) Dr. Wlodzimierz Jarmundowicz & Dr. Pawel Tabakow (Poland)

1) Dr. Carlos Lima and colleagues (Lisbon, Portugal and other countries) implant whole olfactory tissue obtained from the patient (i.e., no immunological rejection) back into the injury site (click on illustration) (J Spinal Cord Med 29(3), 2006). Lima believes that more than one cell type is needed to maximize regeneration, including not only OECs but also olfactory neurons in different developmental stages, and precursor stem cells.

In Portugal, Lima's team has treated 120+ patients from throughout the world, including from the USA (53), Portugal (21), Italy (11), Canada (3), UK (3), and other countries (10). Fourteen patients have also been treated in Columbia, seven in Greece, and six in Saudi Arabia. In addition, new treatment centers are being planned in Japan, India, and New Zealand (September 2006 update). Purportedly, many of the patients have accrued significant benefit.

Lima’s work was featured on an award-winning PBS documentary entitled “Miracle Cells.” In 2005, the World Technology Network named Lima as a finalist for a prestigious innovation award in health and medicine.

The surgery’s critical procedure is the collection of about one fourth of the patient’s olfactory tissue through unique procedures that maximize the harvesting of that tissue and minimize the collection of closely associated nasal respiratory tissue. Although Lima’s experience indicates that small amounts of contaminating respiratory tissue are innocuous, it nevertheless lacks olfactory tissue’s regenerative components. Because olfactory tissue can diminish over time, patient age is important, and as a result, he usually does not accept patients older than 40. Patients regain smelling ability within several weeks.

The injury site is exposed with a laminectomy and then myelotomy (cutting open the cord’s membrane coverings). Although it is impossible to remove all of the scar tissue at the injury site cavity, the scar’s top and bottom stumps are taken off so that the cord is visible, and in between, holes are made in the scar.

The isolated olfactory tissue is dissected into small pieces while it is immersed in a small amount of the patient’s cerebrospinal fluid. The pieces are then implanted into the cavity. Lima estimates that a 1-cm² cavity filled by this tissue will contain approximately 400,000 stem cells and 4 million each of mature neurons, immature neurons, and other supporting cells.

Lima believes maximal restored function will require aggressive rehabilitation. To separate the function-restoring effects of such physical rehabilitation with the procedure itself, many of the more recent patients have been required to initiate physical rehabilitation before the surgery and not just afterwards. For example, the Detroit Medical School has developed an intense rehabilitation program that has treated 34 patients who have undergone olfactory-tissue program.

2) Dr. Hongyun Huang (China) has transplanted olfactory ensheathing cells (OECs) isolated from fetal olfactory bulbs into more than 1,200 patients from 70+ countries with a variety of neurological disorders, including 600+ with chronic SCI. The OECs were isolated from 12-16-week aborted fetuses, and grown and expanded in culture for 12-17 days. For SCI, about a million cells were injected around the injury site exposed through a limited laminectomy. The OECs were often transplanted many years after injury.

Because many patients regain some function soon after surgery, improvement is not due to relatively slow neuronal regeneration or remyelination. Huang speculates that OECs wakeup quiescent neurons that still transverse the injury site, perhaps by altering the injury site’s environment through secreting growth factors and producing adhesion and matrix molecules.

Huang’s SCI work has been summarized in several professional articles. In 2003 and 2006 articles, he reported the results of transplanting OECs into 139 men and 32 women, of which 114 were quadriplegics and 57 paraplegics. Ages ranged from 2 to 64 (average 35) years, and the interval between injury and admission varied from 6 months to18 years. To ensure that improvement was not merely due to surgery-associated decompression, patient MRIs had to indicate the absence of compression before surgery. In addition, the cord had to have some structural continuity through the injury site, the situation for most individuals with SCI.

Function was assessed before and 2-8 weeks after surgery using the ASIA (American Spinal Injury Association) impairment scales, which include motor-function, light-touch, and pin-prick scores. Improvement was noted for each of these scores in five age categories (<20, 21-30, 31- 40, 41- 50, and >50).

Another study evaluated the influence of various factors (e.g., age, sex, time from injury, completeness of injury, and injury level) on OEC-transplantation effectiveness in 300 patients with chronic injuries. Once again, most patients demonstrated some motor and sensory improvement. Those with cervical injuries recovered more function than those with thoracic injuries. No differences were noted among the other injury factors examined.

In 2007, Huang reported the results of following 16 OEC recipients (14 men, 2 women) with MRI imaging for an average of 38 months (6). Ten and six had complete and incomplete injuries, respectively.  The time elapsing from injury ranged from 22 to 55 years. The MRI follow-up imaging of the cord showed the absence of tumors, new or expanding cysts, infection, or neural disruption at the transplantation site, findings which supported the procedure’s safety.

3) Dr. Alan Mackay-Sim’s team (Brisbane, Australia), in a single-blind phase-1 clinical trial, has implanted autologous OECs back into the patient’s injured cord (Brain, published online October 11, 2005). The OECs were isolated from the patient’s nasal tissue and amplified in culture to yield up to 20-million cells over six weeks.  These cells were injected into 40 sites surrounding the injury site. The progress of three male subjects (18-55 years of age) with complete thoracic injuries sustained 6-32 months previously who received OEC transplants are being compared to three individuals who did not have the transplants. These comparative assessments are blinded, i.e., progress-monitoring assessors do not know which patients had the procedure. These periodic assessments included MRI, neurological, psychosocial, ASIA (American Spinal Injury Association), and FIM (Functional Independence Measure) evaluations. The investigators concluded “transplantation of autologous olfactory ensheathing cells into the injured spinal cord is feasible and is safe up to one year post-implantation.”

4) Dr. Tiansheng Sun and colleagues (Beijing, China) have transplanted OECs into 11 patients with SCI. Sun discussed his results at the First International SCI Treatments & Trials Symposium, Hong Kong, December 2005. After exposing the cord with a laminectomy, approximately 500,000 cells suspended in 0.5 milliliters were injected at various locations surrounding the injury site.  There were no procedural complications. Although no motor improvement was noted, significant sensory improvement was observed as measured by ASIA evaluations and a number of patients had a reduction in spasticity.

5) Dr. Wlodzimierz Jarmundowicz, Dr. Pawel Tabakow, and colleagues (Poland) have initiated a phase-I clinical trial to assess the safety and feasibility of transplanting autologous OECs (i.e., obtained from the patient) to treat complete SCI. The procedures were developed on a foundation of preliminary studies using rats and human cadavers. The first operation was performed in June 2008 on a 27-year-old male who sustained a complete (ASIA-A), thoracic T10-11 injury four years earlier from a knife wound.

OECs were isolated from the patient’s olfactory tissue and grown and amplified in culture. Three weeks later, the spinal-cord injury area was exposed through a two-level laminectomy, fibrous adhesions were removed, and a cells suspension of OECs and olfactory fibroblasts were microinjected ~120 times into the area surrounding the injury site. Each injection contained ~25,000 cells. Four weeks after the operation, there were no adverse effects attributed to the procedures. The patient continues neurorehabilitation. The first results on safety and functional outcomes will be announced and published after one-year of observation. Additional patients have been recruited.

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