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Cell Technologies in the Complex Therapy of Spinal Cord Injury: From Trial to Clinical Practice.
A. S. Bryukhovetskiy (1). V. N. Yaryghin (2), V. P. Chekhonin (4), V. B. Karakhan (3), N. G. Evseyev (1), D. N. Dzukayev (5), A. U. Zaytsev (1), M. A. Tulenev (1), I. V. Krasavin (1), A. V. Fadeyev (1), A. V. Lavrentyev (1), V. G. Polyakov (3), I. S. Dolgopolov (3), G. L. Mentkevich (3), N. N. Tupitsin (3), D. P. Tarantsov (1)

First International Spinal Cord Injury Treatments & Trials Symposium (ISCITT) 17-20 December 2005, Hong Kong

The experiment was performed on the model of a complete cut of the spinal cord on Th5 level in 80 Wistar rats. The control arm (20 rats) received the excision of 5mm of spinal cord. The first group (20 rats) received the implantation of the biodegradable polymer matrix "SpheroGel"(BDPMS) with neuroglial cells of rat embryonic olfactory bulb (1 x106) into the site of diastasis. The second group (20 animals) was implanted BDPMS only and the third (20 rats) received BDPMS with hematopoietic stem cells of bone marrow (CD34+). In 2 months, groups 1 and 3 showed recovery of motor functions in 78% and 96% respectively and control of defecation and urination in 61 % and 66% respectively. These functions also restored in 25% of the cases of the control group. The intraventricular infusions of these cell preparations also proved highly efficient.

The limited clinical trial consisted of 46 patients with the spinal cord injury (SCI). The control group included 10 SCI cases (8 males, 2 females, average age 27.8 years, period after injury up to 3 years). The control group patients received conventional surgical treatment: laminectomy, meningoradiculomyelolysis, drainage of CSF cysts and duraplasty.

Eight patients (5 males, 3 females, average age 21.3 years, period after the injury 3-10 years) with severe morphological deficiency confirmed by MRI entered the first arm of the trial. Two patients showed complete anatomical cut of the spinal cord on thoracic level with diastasis 4 and 5 cm. Surgical correction consisted in laminectomy, meningoradiculomyelolysis, CSF cysts'draining, implantation of BDPMS either with autologous glioofactory cells (AGOC) from the sheath of a nose (4 patients) or BDPMS with mobilized autologous stem cells (MASC) (4 cases) into the cyst or the defect of the spinal cord and duraplasty.

The second arm consisted of 18 cases (12 males and 6 females, average age 32 years). The period after the injury was less than a year in 3 cases, from 1 to 5 years in 6 cases and over 5 years in 9 cases. Complete functional cut on various levels of the spinal cord was diagnosed in 11 cases, and incomplete cut confirmed by MRI - in 7 cases.

All patients of this group received no less than 2 (and not more than 8) transfusions of MASC with three months interval. The number of infused mobilized stem cells in average made about 5.3 x 106CD34+ per each transfusion.

All examined patients displayed no changes in neurological disorders for 6 months before admission to the clinic. The therapeutical efficiency was assessed by clinical neurological testing with ASIA scale, FIM scale, ENMG testing with somatosensoric induced potentials, complex urodynamic and immunochemical testing.

The restorative cell therapy given, 61.1 % of the II group cases demonstrated positive changes in motor activity and sensation, 72% of the cases restored the functions of pelvic organs. The data were verified by electroneuromyographic and urodynamic tests. The clinical results were registered beginning from 3-7 days after the intrathecal transfusion of MASC to 7-12 months and persisted for 2 years follow-up. The ability to walk with crutches was restored in 3 cases. It was also found that the internationally adopted Scales do not permit to fully assess and demonstrate the clinical restoration of neurological functions. o

Two patients of the first group showed no clinical improvement. In the first case, the removal of stabilizing construction during reconstructive surgery resulted in the instability of the spine and necessity to repeat orthopedic correction. In the second case the inefficiency of the treatment is probably caused by the psychological attitude of the patient to the recovery.

All other cases clearly displayed motor recovery of limb muscles, improvement of urination and defecation and considerable positive changes in the quality of life and self services. Three patients demonstrated mosaic recovery of pain and temperature sensation. Two patients with complete anatomical cut recovered motion in legs. One of them is able to perform 3 steps supported by crutches. All four patients who received AGOC with BDPMS showed clinical improvement.

Clinical improvement expressed by spasticity reduction and recovery of pain sensation was registered in two patients of the control group after the surgery.

Implementation of the cell therapy for the treatment of SCI opens new perspectives for the damaged functions recovery and considerably improves the life quality of the patients.