Cell transplantation (CT) in treating severe neurological disorders (general information)

NEUROLOGIKAL DISORDERS

Stem cell-based technologies aimed at repairing affected organs at a cellular level open up principally new opportunities in treatment of a diversity of severe diseases, including neurological ones. The Central Nervous System (CNS) is an "immune-privileged" organ where there are natural barriers to the development of alloantigen-induced, immune processes. In fact, grafted cells have been convincingly documented to be able to survive in the major histocompatibility complex (MHC)- incompatible CNS for a long period of time. There is also ample evidence from various experimental studies indicating abilities of the transplanted immature (stem) cells to proliferate and elaborate cell growth factors in the brain lesions and to intensify markedly, thereby, brain tissue regeneration.

The maximal effect of cell transplantation (CT) treatment may be expected when the direct impact of grafted cells on the injured brain site is combined with their influence on different brain structures which are somehow implicated in execution of the damaged function. Such combined effect may be achieved by implantation of donor cells into the liquor circulation. There is now increasing evidence that donor-derived stem and progenitor cells are able to migrate into the damaged tissues and organs and to intensify there regenerative processes. In view of these data, the subarachnoidal way of transplanting donor cells into the injured CNS seems quite reasonable. In addition, such way is minimally traumatic and repeatable.

By special experiments we have found that the fetal-derived stem and progenitor cells are much more effective in restoring the injured nervous tissue than are the adult bone marrow- derived cells. Therefore, the fetal-derived cells were elected to treat neurological disorders at our Center. Before being transplanted, the cells are tested for virus safe in accordance with the most strong international requirements. The cells are grafted into the subarachnoidal cavity of a patient via a lumbar puncture. Moreover, spinal cord injury (SCI) patients typically undergo the surgery aimed to disrupting the intramedullary cyst and to filling up the spinal cord defect by the special gel containing fetal-derived cells (see Spinal Cord Injury section).

Throughout treatment, a patient may be cell-grafted several times.. The results of treating 408 patients with follow-up time of 2 years or longer are presented in Table . It should be pointed out that neurological benefits from stem cell- based therapy are being gradually developed for a long time and, therefore, the presented data are not final and may be changed in the course of time.

The results point out the high efficiency of applying stem cell-based treatment in SCI patients. The majority of such patients noticeably improved the quality of their life Noteworthy is that the appreciable benefits from stem cell-based treatment were noted not only in the patients with recent traumas, but also in whom with time periods after SCI of 1.5 years and longer, and who, in terms of conventional medicine, are considered as incurable (see Spinal Cord Injury section).

Stem cell-based therapy may be effectively applied as early as during acute period after severe brain injure when a patient is unconscious. Such therapy wakens patient’s consciousness, reduces risk of a lethal outcome, and promotes his following neurological rehabilitation (see the section of Traumatic Brain Injury, coma). Our own data also indicate that the long-term neurological defects owing to a traumatic brain injury may be significantly improved by stem cell-based therapy (see the section of Traumatic Brain Injury, long-term neurological defects ). In addition, the significant benefits from cell transplantation treatment were noted in patients with long-term consequences of hemorrhagic or ischemic cerebral strokes (see the cerebral stroke section).

Very impressive results were obtained in children with cerebral palsy. The majority of cell-grafted patients suffered from double hemiplegia, the most severe and the least curable form of cerebral palsy. Nevertheless, stem cell-based therapy enabled those patients to ameliorate significantly their neurological defects and to reduce markedly their dependence upon overall outside assistance (see the Cerebral Palsy section).

It should be noted that cell-based therapy may result in a decrease of readiness for convulsions in epileptic patients. With this therapy, such patients become much less dependent on taking anticonvulsants.

Evident clinical improvements were noted in patients with long –term consequences of neuroinfections It should be emphasized that all patients of this group had initially very profound neurological defects and were refractory to conventional cure.

Of great interest is the first positive experience of treating the congenital diseases such as spinal amyotrophy and Down's syndrome, for which no effective treatment is still found.

The inefficiency of treating a posthypoxic encephalopathy might be explained by a large extent to which brain lesions has spread.

The low efficiency of stem cell-based treatment in the cases with degenerative diseases such as multiple sclerosis and Parkinson’s disease may be presumably explained by failure of the grafted cells to interrupt chronic pathological processes underlying those diseases.

The primary targets for acting the grafted cells may be the most ancient stem structures of the brain. Activation of those structures probably provides “ awakening ” cerebral brain cortex in comatose patients. On the other hand, the lasting regress of focal symptoms in cell-grafted patients may be evidence of developing new stable neural communications.

Subarachnoidal cell transplantation is commonly safe and well tolerated. Meningisms, but also rises in body’s temperature up to 38.5 C, were noted in a part of patients during 24-to-48 h after transplantation. Those occurrences disappeared, by themselves, not requiring any additional serious medical interventions. The performance of stem cell-based therapy in pediatric practice requires, however, special attention because of the possibility of developing in cell-grafted children the acute encephalitic reactions, rapid relief of which should be carried out under conditions of the reanimation department. It is of great importance to note that a long-term follow-up (2 years and longer) of cell-grafted patients revealed no complications which might be related to the grafted cells.

Thus, stem cell-based therapy is sure to open new opportunities to treat effectively severe neurological disorders of different genesis. It should be particularly emphasized that such therapy is able to ameliorate neurological defects and improve a quality of life in those cases when all other medical interventions are powerless.

Table. The outcomes of applying stem cell-based treatment in patients with severe neurological disorders.

№ NOSOLOGICAL TYPE Number of patients Numberof CT CLINICAL OUTCOME
good or satisfactory doubtful or lacking
1 CONSEQUENCES OF SPINAL CORD INJURY 102 300 70 (69%) 32(31%)
2 CONSEQUENCES OF BRAIN INJURY 80 154 70 (90%) 10 (5%)
3 COMA IN CONSEQUENCE OF BRAIN INJURY) 52 93 46 (88%) 6 (12%)
4 CONSEQUENCES OF CEREBRAL STROKE 17 23 13 (76%) 5 (24%)
5 CONSEQUENCES OF NEUROINFECTION 11 22 9 (82 %) 2 (18%)
6 INFANTILE CEREBRAL PALSY 115 295 92 (80%) 32(31%)
7 SPINAL AMIOTROPHY 2 6 2 (100%) 0(0%)
8 DOWN’S SYNDROME 1 1 1 (100%) 0(0%)
9 POSTHYPOXIC ENCEPHALOPATHY 13 37 2 (15%) 11 (85%)
10 DEGENERATIVE DISEASES 17 18 1 (6%) 16 (94%)
  TOTAL 408 949    

For more information see the publications .

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