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News about stem cells
Stem cell treatment protects bone marrow from damaging chemotherapy effects in cancer patients
12 May
Stem cell therapy can protect cancer patients from damaging side-effects of chemotherapy, a new trial in the US suggests.
New Approach to Treating Muscular Dystrophy With Stem Cells
05 May
Scientists from the Lillehei Heart Institute (University of Minnesota) have developed a new efficient process of making muscle cells from human stem cells and for the first time ever effectively treated with these cells muscular dystrophy in a mice model.
A New Brain Stem Cell Discovered
29 April
Adult brain contains stem cells, and Researchers at Lund University (Switzerland) found a new type of these cells.
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Treatment of Patients with Remitting-Relapsing Multiple Sclerosis


Observed were 13 cases with remitting–relapsing multiple sclerosis, among them 5 female patients and 8 male patients. Age of patients varied from 19 to 28, mean age being 25.3±2.47 years. Duration of the diagnosed multiple sclerosis varied form 8 months to 3.5 years (mean 2.13±0.26 years). Duration of remission in this group lasted from 2 months to 1 year, usually being 3-6 months. Since the onset, we observed worsening of symptoms and residual effects from attack to attack in most patients (10 individuals).

Clinical symptoms in MS patients were evaluated using the 4-score scale: 0 – absence of sign; 1 – mild sign; 2 – moderate sign; 3 – severe sign; 4 – extremely severe sign. The Table 1 presents the mean score in patients demonstrating a certain sign and the number of such patients (N). The symptoms were evaluated during the remission.

By the beginning of the fetal stem cell transplantation, this group of patients most frequently demonstrated pyramidal, sensory and visual disturbances of different degree (Table 1).

Table 1. Clinical Profile of Patients with Remitting-Relapsing MS (n=13)

Symptom N Symptom intensity, score (0–4)
Before
transplantation
 After transplantation, years
1 2 3 4
Pyramidal symptoms:
8          
spasticity 5 3–2 2 2 1 1–0
elevation of deep reflexes 6 3 3–2 2 2–1 2–1
diminished superficial abdominal reflexes 6 3–2 2 2 2–1 2–1
pathological extensor plantar reflexes 5 2 2 2 2–1 2–1
Ophthalmological symptoms: 8          
optic neuritis 5 3 2 2 2–1 2–1
diplopia 5 2 1 0 0 0
nystagmus 4 3–2 1–0 0 0 0
convergence disturbance 4 3 1–0 0 0 0
Sensitivity disturbances: 9          
paresthesia 7 2 2 2 2–1 1
hyperesthesia 4 2 2–1 1 1 1
hypesthesia 2 2 2–1 2–1 1 1
Ataxia 4 3–2 2 2 2 2
Coordination tests
3 2 2 2–1 1 1
Dysarthria 3 3 3–2 3–2 2 2–1
Dysphagia 2 3–2 2 2 2 2
Weakness in the extremities 6 2 2–1 1 1 1
Fatigue 9 3–2 2 2 1 1
Cognitive dysfunction: 8          
memory decline 6 3–2 2 2 1 1–0
attention impairment 4 3–2 2 2 1 1
slowed information processing 4 2 2–1 2–1 1 1
Depression 4 3–2 2 2–1 1 1–0
Dizziness and vomiting 3 2 1 1 0 0

After the stem cell treatment, this group of patients demonstrated gradual reduction in clinical manifestations of the focal lesions of the central nervous system. Significant positive dynamics was noticed in such symptoms as nystagmus, convergence disturbance, spasticity, coordination disorders, depression and cognitive dysfunction. Usually, these disturbances resolved within the first year of our follow up after the transplantation.

Other disturbances were more resistant, their manifestations persisted during several years, and their reduction was not so clear. These are such manifestations as dysarthria, dysphagia, pathological reflexes and ataxia. These differences must be due to different degree and location of the damage in the central nervous system.

Stem cell treatment significantly improved mental state of MS patients, and we believe this effect is due not only to neurological improvement that gave the patients a hope for recovery after the continuous inefficient routine treatment but also due to the positive effect of fetal stem cells on the emotional sphere.

During the observation period (2 to 5 years) no exacerbations were noticed in this group of patients, although most of them suffered them regularly before the treatment. No disease progression as well as progression-related increased disability was observed either.

MRI results demonstrated the decrease of foci volume in the mean by 31%, decrease in number of foci following the gadolinium contrast by 48%, and reduction of the specific density of the foci in T2-regime. This evidences for the significant improvement of demyelinisation processes in the central nervous system.

Immunological test results (in 8 patients of the group) before the beginning of the fetal stem cell treatment showed depression of T-cell immunity – evident decrease of average number of CD3+lymphocytes (by 20.1%), CD8+lymphocytes (by 15.4%), increase of immunoregulatory index (by 15.3%), and activation of humoral immunity (elevation in lymphocyte count with CD19+ phenotype (in the mean by 38.1%), and class G immunoglobulins by 32.7% (p<0.05). Other indices didn’t have significant deviations from the reference rate (Table 2).

After fetal stem cell transplantation, the average level of lymphocytes with CD3+ phenotype has reliably increased in comparison with the initial level, although it was still lower than normal by 9.0% (p<0.05). In 6 months after the treatment, this index increased in the mean by 5.7% and statistically didn’t differ from the norm.

T-helpers (CD4+) demonstrated mild and unreliable tendency for elevation. Within 6 months, their number gradually increased on average by 7.7%.

The number of T-suppressors (CD8+lymphocytes) in one month after the transplantation increased and statistically didn’t differ from the norm, and in 6 months after the transplantation their level elevated again (in the mean by 20.5%) and achieved the initial level.

Immunoregulatory index reflected definite shifts of the cell immunity and increased with the elevation of the CD8+lymphocyte level. In one month after the transplantation, the average immunoregulatory index was 1.74±0.05, i.e. it decreased by 7.6%, and in 6 months after the treatment it remained stable.

The decrease in CD19+ lymphocyte level that was initially increased was noticed in one month after the transplantation (by 17.2%). In 6 months, the average level of CD19+ lymphocytes was reported to decrease more, in the mean by 21.7% (p<0.05), in comparison with the initial level.

Class G immunoglobulins level also gradually decreased, and in one month after the transplantation it reduced by 12.0%, and in 6 months – by 19.3%.

Thus, we can conclude that fetal stem cell transplantation has a significant immunomodulatory effect on the immune system of MS patients. Our study confirmed the elevation of the lowered indices of the cell immunity and decrease of the elevated indices of the humoral immunity (CD19+lymphocytes and IgG) in one month after the fetal stem cell transplantation, and this tendency persisted within the period of our study (6 months).

Table 2. Immunity Indices in Patients with Remitting-Relapsing Multiple Sclerosis (n=8)

Indices  Reference Rate  

Before transpl.
After transplantation
In 1 month  In 6 months
M±m M±m M±m M±m
Lymphocytes, 109        
CD3+
(Ò-lymphocytes)
1.34±0.02 1.07±0.04* 1.22±0.03*# 1.29±0.04#
CD4+
(Ò-helpers)
0.86±0.01 0.78±0.05 0.81±0.04 0.84±0.02
CD8+
(Ò-suppressors)
0.52±0.01 0.44±0.02* 0.48±0.02 0.53±0.02#
CD4+/CD8+ 1.63±0.04 1.88±0.03 1.74±0.05 1.71±0.06
CD19+
(Â-lymphocytes)
0.21±0.06 0.29±0.03 0.24±0.02 0.23±0.01
CD16+
(NK-cells)
0.39±0.01 0.34±0.04 0.41±0.03 0.36±0.02
Immunoglobulins IgG 11.3±0.78 15.0±0.81* 13.2±1.12 12.1±0.58

Note: * - validity coefficient in comparison with the reference rate p<0,05; # - validity coefficient in comparison with the rate before the transplantation p<0,05.

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