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OTHER CELL TRANSPLANTATION

Laurance Johnston, Ph.D.

Sponsor: Institute of Spinal Cord Injury, Iceland

 

 

1) Dr. Fernando Ramirez (Mexico)

2) Diacrin Corporation (USA)

3) Dr. Hui Zhu (China)

4) Drs. Masoumeh Firouzi, Hooshang Sabveri (Iran)

5) Dr. Xian-Hu Zhou (China)

6) Miami Project to Cure Paralysis (USA)

1) Dr. Fernando Ramirezíteam (Mexico), starting in the early 1990ís, has transplanted blue-shark, embryonic neuronal cells (i.e., xenogeneic transplantation) into the injured spinal cord of 89 patients with SCI. His approach evolved from live-cell therapies developed by European scientists starting in the 1930s long before stem cells emerged as a hot scientific topic. Although his work is still considered controversial, it is less so today than when he started his work because of all the other cell-transplantation work that has since been initiated. More recently, the program has shifted to the use of umbilical cord stem cells (www.ramirezdelrio.com).

2) The Diacrin Corporation (USA) sponsored another xenotransplantation clinical trial. Specifically, Drs John McDonald (St. Louis, Missouri) and Darryl DiRisio (Albany, New York) injected about 14-million, immature, fetal pig, myelin cells into the cord surrounding the injury site of 10 patients with chronic SCI. The purpose of these cells was to remyelinate neurons that have lost their insulating myelin sheaths due to injury, in turn, restoring conduction potential. Because the expression of immune-provoking proteins located on the porcine cell surface was altered, the need for immune-suppressing drugs was supposedly greatly reduced.

Few results were reported for this clinical trial. According to a December 2002 investment report, the survival of the transplanted porcine cells was minimal, even with immunosuppressant drugs.

3) Dr. Hui Zhu (China): As reported at the 1st International SCI Treatments & Trials Symposium, Hong Kong, December 2005, Dr. Hui Zhu and colleagues have transplanted fetal Schwann cells into 40 individuals with complete paraplegia. Thirty-two were men and eight were women; age ranged from 18-58 (average 31) years; and time between injury and transplantation ranged from 1-19 years, i.e., all were chronic injuries. Patients were followed for 3-24 months using ASIA assessments, MRI imaging, and various electrophysiological evaluations.

Procedurally, Schwann cells cultured from fetal human sciatic nerve (a nerve that runs through upper leg) were implanted into the patientís injury cyst or cavity. After surgery, patients received ambulatory training. Although a few regained substantial function, in most patients improvements were slight as measured by ASIA evaluations of motor function and light and deep sensation. In some patients, the MRI and electrophysiological assessments indicated partial recovery of spinal-cord function.

At the aforementioned symposium, Zhu showed a case-study video of a young man who regained substantial function due to the intervention.  

4) Drs. Masoumeh Firouzi, Hooshang Sabveri and colleagues (Iran) have also transplanted Schwann cells into the injury site. As indicated earlier, these neuronal support cells remyelinate axons in the peripheral nervous system, which, unlike the central nervous system has considerable inherent regenerative potential.

This human trial builds upon on a recently published study using rats with an experimental contused injury, the sort of injury that is most common in humans. In this study, Schwann cells were injected into the subarachnoid space surrounding the spinal cord.  Compared to control animals, the treated rats regained more locomotion after injury and had more spared axons.

Given these results, the investigators received permission from the Tehran University of Medical Sciencesí ethical committee to transplant Schwann cells into 20 patients with SCI. The cells were isolated from a sural nerve in back of the patientís calf (i.e., autologous cells with no rejection potential) and cultured in a sterile laboratory for two to five weeks. The cultured cells were then implanted back into the injury site.

Initially, nine of the 20 authorized patients were treated. This study excluded individuals older than 50, whose cord has been transected, and whose injury site is considered too extensive. A number of the treated patients had long-term chronic injuries, including patients 16, 23, 25 years post injury. Using the data coming out this preliminary study, more definitive criteria will be developed on the most appropriate post-injury, treatment window.

Three to six months after implantation, no adverse side effects have been observed. According to Dr. Firouzi, all treated patients ďhave shown some degree of sensory recovery; most have motor recovery findings using quantitative (digital) motor evaluations; and some showed sphincter and sexual improvement, all compared to the patientís steady-state before the transplantation. Three of them can walk now (two using parallel bars and one using walker).Ē The investigators note that progress should continue for some time after this limited follow-up period.

At that point in time, preliminary preparations were being made to develop facilities and train other doctors to make the procedures more accessible to the general SCI community.

In 2008, the investigators published the results of treating four patients with mid-thoracic injuries with autologous Schwann cells. Age ranged from 22 to 43 years, and they had been injured 28 to 80 months before treatment. As indicated before, the patientís sural nerve was the source of the transplanted Schwann cells. The patients were followed for one year using ASIA-impairment, sphincter, sexual-function, and MRI assessments. Of the four patients, only one with an incomplete injury, who had extensively rehabilitated, demonstrated motor and sensory recovery one year post transplantation. No adverse effects were observed. From these preliminary findings, the investigators concluded that ďautologous Schwann cell transplantation is generally safe for the selected number of SCI patients but it does not prove beneficial effects.Ē

In 2011, the investigators reported two-year follow-up results of 33 individuals treated with transplanted autologous Schwann cells as described above. With an average age of ~ 33 (range 23-50) years and duration of injury 4.1 years, 22 were men and 11 women. Twenty-four and nine patients had thoracic and cervical injuries, respectively. All had either ASIA-A-complete or ASIA-B (some sensory function) injuries (see appendix). Follow-up results indicated that the transplantation procedures were generally safe. Small improvements were observed in 1) light-touch sensation, especially in those with cervical lesions, and 2) motor function, particularly in those with more recent cervical injuries. Several patients reported new urinary and/or bowel sensation and control.

5) In 2012, Dr. Xian-Hu Zhou and colleagues (China) reported treating six individuals with SCI with autologous (i.e., from the patient) Schwann cells. All except one were men, age ranged from 7 to 34, and the time between injury and transplantation varied from one week to 20 months. A Schwann-cell-containing sural nerve segment was surgically removed from the patientís leg, the resulting tissue incubated in culture, and the Schwan cells isolated. After exposing the cord, the Schwann cells were injected into the area adjacent to the injury site. The patients were followed for at least five years using a variety of assessments. Although the study had limitations due, in part, to its small size, all patients showed some signs of improvement in autonomic, motor, and sensory function.

6) Investigators at the Miami Project to Cure Paralysis (USA) have received permission from the Food and Drug Administration to initiate a phase 1 clinical trial assessing the safety of transplanting autologous Schwann cells into eight patients with acute thoracic injury.  To obtain the Schwann cells, a biopsy of sensory nerve in the leg will be carried out, and the resulting tissue cultured for three to five weeks to obtain the necessary number of cells for transplantation. All subjects will be followed for one year.

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