Stroke is a global medical and socio-economic problem and a great demand for alternative therapies, the leading one being stem cell (SC) therapy. Pathogenetic processes in ischemic stroke (II) trigger the mechanisms of necrotic and apoptotic death of neurons with the formation of the central infarct zone («core of ischemia») and the ischemic «penumbra» zone; the severity and reversibility of the injury directly depends on the duration of ischemia. In parallel with pathogenetic processes, endogenous neurogenesis occurs – the proliferation of neurogenic stem and progenitor cells (NSC/NPC) and their migration into the ischemic focus; however, most NSCs and newly formed neurons undergo apoptosis and recovery of lost functions does not occur. Significant efforts are being made to find ways to control neurogenesis, in particular through the transplantation of exogenous SCs. The main factors preventing the use of SCs in humans are moral, ethical, religious and legal aspects related to the source and method of obtaining cells, as well as possible immunocompromised complications due to incompatibility of donor cells with the recipient of the main histocompatibility complex antigens. The safest is the use of autologous SCs (the patient’s own cells), as it does not require the use of immunosuppressive protocols. Due to the relative safety and ease of production, the most common are multipotent mesenchymal stem cells (MSCs), namely MSCs of the bone marrow (BM). Numerous preclinical studies in experimental animals with modeled II, as well as clinical trials conducted over the past 15 years, have shown the safety and feasibility of transplantation of autologous MSCs in patients with severe neurological deficits after II. Two different approaches to the use of MSCs are discussed: neuroprotection in the acute phase and neurorestoration in the chronic phase II. Proposals are currently being developed for phase II/III clinical trials in acute and chronic stroke using BM MSCs, the results of which will form the basis for certified standardized II treatment protocols.
The aim of the work was to study the impact of fetal rat brain cell supernatant (FRBCS) on the expression of transforming growth factor β1 (TGF-β1) and p53 in C6 cells of rat glioma in vitro. Materials and Methods: FRBCS was obtained from suspensions of fetal rat brain cells on the 14th (E14) day of gestation. C6 glioma cells were cultured for 48 h in the presence of FRBCS or FRBCS + anti-TGF-β1 monoclonal antibody. Immunocytochemical staining for TGF-β1 and p53 was performed. Results: The proportion of TGF-β1-immunopositive tumor cells in C6 glioma cultures was statistically significantly higher than in the control cell cultures of normal fetal rat brain. FRBCS reduced the proportion of TGF-β1-immunopositive tumor cells and increased the proportion of p53-immunopositive cells in C6 glioma cultures. In cells cultured with FRBCS + anti-TGF-β1 monoclonal antibody, the above effects of FRBCS were abrogated. Conclusion: The obtained results suggest that TGF-β1 seems to be responsible for decrease in TGF-β1 expression and increase in p53 expression in C6 glioma cells treated with FRBCS.
To evaluate the infl uence of the rat progenitor neurogenic cells supernatant (RPNS) on the transplantable rat malignant brain glioma cells (strain 101.8) under conditions of cultivation. Methods. primary cultures were obtained from glioma 101.8 fragments (n = 12) and intact brain of newborn rats (n = 9). RPNS was received from neurogenic cell suspensions of fetal rat brain on 8-11 th (E8-11) and 12-16 th (E12-16) days of gestation. Results. RPNS (E8-11) as well as RPNS (E12-16) showed a cytotoxic effect on the glioma 101.8 cells in short-term cultures, the level of which was dose-dependent and intensifi ed with increasing duration of incubation. RPNS (E12-16) had a more pronounced cytotoxic action on the cells of glioma 101.8 compared with RPNS (E8-11). The cytotoxic index (CI) of RPNS (E12-16) on the glioma 101.8 cells was signifi cantly higher than CI determined in cell suspensions of normal rat brain (CI was (91.99 ± 2.37) % and (22.9 ± 4.97) % respectively over 48 h incubation with RPNS). After RPNS (E8-11) infl uence on the glioma 101.8 primary cultures the signs of dose-dependent cytotoxic effects were observed: the thinning of growth areas, appearance of dystrophic and necrobiotic changes in tumour cells and decreasing of a mitotic index. These features were strengthened under the RPNS (E12-16) infl uence. Conclusions. fetal RPNS showed dose-dependent cytotoxic and antiproliferative effects on the cultivated glioma 101.8 cells, which were intensifi ed with the increasing of rat brain gestational age and lengthening of the incubation duration. A prerequisite for such effects is likely the NPC ability to produce the substances with antitumour activity. K e y w o r d s: progenitor neurogenic cells, rat fetal brain, supernatant, glioma 101.8, cytotoxic index, mitotic index.
Вивчали дію супернатанта прогеніторних нейроклітин (СНК) на цитотоксичну функцію лімфоцитів у щурів за умов фізіологічної норми та експериментально змодельованого пухлинного процесу (гліома головного мозку, штам 101.8 ВСТУПВажливою проблемою імунології злоякісних пухлин і, зокрема, гліом головного мозку є визначення механізмів їх «вислизання» з-під нагляду імунної системи та її пригні-чення. Відомо, що при гліомах -найбільш загальних первинних пухлинах мозку, які характеризуються інфільтративним ростом, резистентністю до лікування і мають не-сприятливий прогноз для життя пацієнтів, виявляються зміни у всіх ланках імунітету [1]. Гліома формує імуносупресивне оточен ня секрецією різних молекул (простагландину Е2, інтерлейкіну-10 -IL-10, трансформую-чого ростового фактора b -TGF-b, гангліо-зидів) для послаблення імунної відповіді [2]. Поряд зі зниженням кількості та функції імунокомпетентних клітин (відносна та аб-солютна лімфопенія, знижений вміст лімфо-цитів CD4 + , CD8 + , CD16 + , HLA-DR + -клітин, гальмування проліферативної здатності лімфоцитів, зниження секреції ефекторних цитокінів), підвищується кількість Т-регуля-торних клітин CD4 + CD25 + FoxP3 + , що проду-кують імуноінгібувальні медіатори [3]. При гліомах, особливо злоякісних, відбувається часткова або повна втрата клітинами пухлин експресії антигенів І та/або ІІ класу головно-
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