Different effect of testosterone on polypotential stem hematopoietic stem cells and immunocompetent B-lymphocytes]

A research was made to study the dynamics of the proliferative, colony-forming and migration capacity of stem hemopoietic cells in (CBA X C57Bl) F1 hybrid mice under the influence of testosterone propionate, 10 mg/100 g, as well as the migration of immunocompetent B lymphocytes from the bone marrow to the spleen and the accumlation of their progeny, antibody-producing cells, in the spleen. The immunodepressive effect of testosterone was manifested by a decrease in the migration of B cells and the number of antibody-producing cells in the spleen. On the contrary, testosterone had a stimulating effect on the functional activity of stem hemopoietic cells, increasing their proliferation and migration. Under conditions of the suppressed erythropoietic differentiation of multipotent stem hemopoietic cells the injection of testosterone resulted in an increase in the number of antibody-producing cells in the spleen. This suggests that the stimulation of erythropoiesis and immunosuppression, induced by testosterone, are interconnected and determined by the direct action of the hormone on the cellular cycle of the stem cells, as well as by their prevailing differentiation towards the erythroid series, resulting in the decrease of their differentiation into B cells.     

Influence of the maternal effect on allogenic inhibition of hematopoietic stem cells]

Bone marrow cells (0,5-10(6)) of female mice of CBA or C57BL strains were injected intravenously to lethally irradiated CBA, C57BL/6, (femaleCBA X maleC57BL/6)F1 and (femaleC57BL/6 X maleCBA)F1 mice. Spleen of recipients as assayed for colony count on the 9th day after bone marrow transplantation by the method of Till and McCullouch. Stem cells of CBA mice demonstrated failure of allogenic inhibition in (CBA X C57BL/6)F1 hybrid mice and formed the same number of colonies as in the spleen of syngenic recipients. The level of allogenic inhibition of CBA stem cells transplanted to (C57BL/6 X X CBA)F1 hybrid mice was 50%. Bone marrow cells of C57BL/6 mice formed colonies in spleen of (CBA X C57BL/6)F1 mice at least in 20 times less than in syngenic combination. In the transplantation of bone marrow from C57BL/6 mice to (C57BL/6 X CBA)F1 hybrid mice the allogenic inhibition was less pronounced (77-85%) as compared with the transfer of cells to (CBA X C57BL/6)F1 hybrid mice (95%). The sex of a recipient did not influence the number of formed colonies. The different level of allogenic inhibition of parental stem cells can not be explained by the effect of linkage with sex as the female of reciprocal hybrid mice have identical structure of sex chromosomes (X(CBA)XC57BL/6). The data obtained indicate that the maternal effect affects allogenic inhibition of stem cells in parent--F1 system. It is possible that the maternal influence may be determined by cytoplasmic factors of inheritance which affect the expressivity of recessive genes Hh, controlling the inheritance of specific haematopoietic cell antigens.     

Effect of syngenic lymphocytes on allogenic inhibition of hematopoietic stem cells of embryonic liver]

The transplantation of liver from the embryos and newborn C57BL-6 mice to the lethally irradiated hybrids (CBA X C57BL/6) F1resulted in 90% allogenic inhibition of the colony-forming activity of the donor elements. The degree of allogenic inhibition of liver cells of 19 days old embryos and newborn mice may be changed with the help of syngenic lymphocytes of adult mice or delayed transplantation of cells 72 hrs following the irradiation of recipients but these procedures proved to be ineffective with the liver cells of 13 and 16 days old embryos. A suggestion is put forward to the effect that the allogenic inhibition is based on the active reaction of recipient hybrids (CBAXXC57BL/6) F1 to the stem hemopoietic cells of C57BL/6 mice.     

The dual nature of lymphocyte interaction with allogenic stem cells

The interaction of lymphocytes from mouse lymph nodes with allogeneic stem cells was studied using exogenous colony formation inhibition test. Dual nature of the interaction was revealed: great amounts of lymphocytes inhibited, while small amounts stimulated colony formation. This dependence holds true for macro- and microcolonies as well as for erythrocyte and granuloid microcolonies in the bone marrow during fixation on day 8 and 11 after cell mixture transplantation.     

Inactivation of stem cells by allogenic lymphocytes: competition between T1- and T2-subpopulations]

Transplantation of the bone marrow cells with allogeneic T-lymphocytes to the irradiated hosts was accompanied by inactivation of the stem elements of the graft. The lymph node cells of T-mice (those deprived of B cells) were more active than the spleen cells of these mice. The stem cells inactivation was weakly expressed or absent in case of a combined acti-n of T-cells from the lymph nodes and the spleen.     

Temporary characteristics of the process of stem cell inactivation by allogenic lymphocytes]

The time during which transplated lymphocytes block proliferation and differentiation of non-syngeic stem cells has been determined by retrasplantation of immuno-competent cells from one lethally irradiated recipient to another one. It was established that process of inactivation of CFU by allogeneic lymphocytes proceeds itwo stages. At the first stage, the colonization of recipient's tissues takes place. The colonization of tissues and processes of early recognition are completed during the first hours after transplantation of cell mixtures. At the second stage, the processes of redistribution of injected cells occur and a complete inactivation of stem cells take place. These events are completed in bone marrow and spleen 4-5 days after transplantation of cells mixture, possibly with the participation of lymphocytes sensibilized with the target-cells.     

Characteristics of cytotoxic t-lymphocytes eluted from allogenic target cells]

Gain in the specific cytotoxic effect of immune lymphocytes after their absorption on the corresponding target cells (TC) and subsequent elution with pronase was caused not by the increase of the cytotoxic activity of individual cells, but by the quantitative enrichment of the population with the effector T-cells. Eluted and the initial immune lymphocytes failed to differ by the kinetics of absorption on the TC. The eluted lymphocyte fraction was characterized by a two fold increase in the T-cell content and a 4-5-fold increase in the number of DNA-synthesizing cells on account of an increase in the content of medium and large lymphocytes.     

Role of T- and B-lymphocytes in the heterogeneity of human cell-mediated reactions to bacterial antigens]

Leucocytes from 30 patients with allergy to tuberculin and bacterial antigens were treated with antithymus (ATS) and anti-immune globulin (AIGS) sera. The leucocyte migration inhibition test (LMIT) was performed with these antigens. ATS abolished the LMIT induced by tuberculin and sometimes by bacterial antigens (staphylococcal, streptococcal etc.). AIGS frequently abolished the LMIT induced by bacterial antigens, but not by tuberculin. In some cases the treatment with any serum abolished the LMIT induced by the antigens, or, on the contrary, it was abolished only by a successive treatment with both sera. The lymphocyte types (T or B) determining the secondary immune response to the same antigen are different in various patients, as well as they differ in the same patients in relation to diverse antigens. Five types of lymphocyte - antigen interrelation in the LMIT have been distinguished.     

Inactivation of the colony forming cells in bone marrow by allogenic T-lymphocytes]

Bone marrow cells together with allogeneic cortisone-resistant thymocytes or the lymph node cells of intact mice treated with antilymphocytic T or O-antisera were transplanted to the lethally irradiated mice. The antisera eliminated the capacity of T lymphocytes to inactivate allogeneic stem cells. Cortisone-resistant thymocytes displayed a strong inactivating action. The principal role in the processes of inactivation of genetically foreign stem cells was played by T lymphocytes. B lymphocytes possessed no properties of killer cells. The presence of B lymphocytes in the population of killer cells apparently failed to serve as a determinant one for the development of inactivation processes.     

Role of stem cells in cancer therapy and cancer stem cells: a review

For over 30 years, stem cells have been used in the replenishment of blood and immune systems damaged by the cancer cells or during treatment of cancer by chemotherapy or radiotherapy. Apart from their use in the immuno-reconstitution, the stem cells have been reported to contribute in the tissue regeneration and as delivery vehicles in the cancer treatments. The recent concept of 'cancer stem cells' has directed scientific communities towards a different wide new area of research field and possible potential future treatment modalities for the cancer. Aim of this review is primarily focus on the recent developments in the use of the stem cells in the cancer treatments, then to discuss the cancer stem cells, now considered as backbone in the development of the cancer; and their role in carcinogenesis and their implications in the development of possible new cancer treatment options in future.     

Cytotoxic serum against B-lymphocytes obtained by immunization with bone marrow cells]

Immunization of rabbits with the bone marrow cells of intact mice permitted to obtain antisera selectively reacting with the cells of the bone marrow origin. A method of obtaining the anti-B-sera by immunization of animals directly with the bone marrow cells permitted to exclude irradiation and thymectomy of mice, this serving as necessary steps of the methods described formerly.     

miR-124 promotes proliferation and differentiation of neuronal stem cells through inactivating Notch pathway

Background

Neural stem cells (NSCs) are able to differentiate into neurons and astroglia. miRNAs have been demonstrated to be involved in NSC self-renewal, proliferation and differentiation. However, the exact role of miR-124 in the development of NSCs and its underlying mechanism remain to be explored.

Methods

Primary NSCs were isolated from embryos of Wistar rats. Immunocytochemistry was used to stain purified NSCs. miR-124, Delta-like 4 (DLL4), ki-67, Nestin, β-tubulin III, glial fibrillary acidic protein (GFAP), HES1, HEY2, and cyclin D1 (CCND1) expressions were detected by qRT-PCR and western blot. The interaction between miR-124 and DLL4 was confirmed by luciferase reporter assay. Cell proliferation was assessed by MTT assay.

Results

NSCs could self-proliferate and differentiate into neurons and astrocyte. miR-124 was up-regulated and DLL4 was down-regulated during NSC differentiation. DLL4 was identified as a target of miR-124 in NSCs. Ectopic expression of miR-124 or knockdown of DLL4 promoted the proliferation and the formation of NSCs to neurospheres. Moreover, miR-124 overexpression or DLL4 down-regulation improved β-tubulin III expression but decreased GFAP expression in NSCs. Furthermore, enforced expression of DLL4 partially reversed the effects of miR-124 on NSCs proliferation and differentiation. Elevated expression of miR-124 suppressed the expressions of HES1, HEY2, and CCND1 in NSCs, while these effects were attenuated following the enhancement of DLL4 expression.

Conclusion

miR-124 promoted proliferation and differentiation of NSCs through inactivating Notch pathway.

     

Effect of different temperature fractions of RNA on allogenic inhibition of hematopoietic stem cells of mouse bone marrow and embryonal liver]

In the system of non-syngeneic transfer of stem hemopoietic cells, the preliminary incubation of the cells of bone marrow or embryonic liver of the C57BL mice with different temperature RNA fractions isolated from the spleen of (CBAXC57BL) F1 was shown to lead to the complete or partial restoration of the colony forming ability of the donor cells. The 63 degrees RNA fraction was shown to have the greatest restorative effect.     

Autologous and allogenic human rosettes]

A proportion of human peripheral blood T lymphocytes have the property to form spontaneous rosettes in vitro with autologous and allogeneic red blood cells. In our experience the percentage of allo-rosettes is higher than the percentage of auto-rosettes. Red blood cells of the Bombay type are capable of binding to allogeneic lymphocytes. However a low percentage of auto-rosettes was found in the Bombay donor.     

Induction of T-suppressor cells by immunization with allogenic spleen cells in the H-2 system of mice]

The nature of suppressor cells induced by immunization with the allogenic spleen cells and inhibiting the DNA synthesis activation in the mixed lymphocyte culture was studied. Suppressor cells are resistant to mitomycin C and carrageenan. They are not inactivated by the treatment with rabbit anti-B- and anti-Ig- as well as with mouse antibodies (anti-Mls serum) against B lymphocytes in the presence of complement but eliminated by rabbit anti-lymphocyte and anti-T globulins and by mouse anti-theta serum. These T suppressor cells are concentrated in the large lymphocyte fraction in the ficoll gradient. Their blocking of the DNA synthesis activation is evidently non-specific.     

The stem cells of animal tissues]

A brief historical review of concepts on stem cells is given with a stress made on the role of Russian scientists A. A. Maksimov and A. A. Zavarzin who have formulated key problems in biology of stem cells and cell renewal. Principal stages in current studies of stem cells are considered. An outline is given of traditional and recent trends in the investigations: comparative studies of tissue systems with stem cells; molecular genetic mechanisms of the self-maintainance and the differentiation of stem cells; stem cells as a subject of gene engineering.     

Self-maintenance of migrating hematopoietic stem cells]

Decreased self-maintenance ability of the migrating stem cells (CFU) from the peripheral blood or ectopic focus of hemopoiesis in comparison to the settled bone marrow CFU, as measured by the spleen colony method or by means of chromosomal markers, has been studied. The competence for myeloid and lymphoid differentiation was essentially the same for migrating and settled stem cells.