


Vol 6, No 2 (2011)
- Year: 2011
- Articles: 14
- URL: https://genescells.ru/2313-1829/issue/view/6175
Articles
Interview with professor Alejandro Madrigaland professor Manuel Fernandez
Abstract
- Dear gentlemen, first of all, let me thank you
for finding time to visit our symposium. We conduct
such events on an annual basis, but this is the first
time it covers issues in the field of hematology.
You are well-known top specialists. Why did you
agree to participate and give lectures.
Genes & Cells. 2011;6(2):6-9



Clinical importance of maternal microchimerism in children
Abstract
Bilateral exchange with blood cells and cell-free substances
between a mother and a fetus and visa verse routinely occurs
during normal pregnancy. A term of microchimerism (MC)
implies a few number of cells (or DNA) detected in a child and/
or a mother which primarily originated in a genetically different
individual. Whereas MC might result from iatrogenic exposure
on an organism such as transplantation or transfusion, the
main source of MC is a naturally acquired condition as a
result of transplacental interactions between a mother and
a fetus during pregnancy. The present interest to MC can
be explained by many reasons. During pregnancy fetal cells
can be found in a mothers blood in prenatal diagnostics.
Moreover, investigation of fetal MC might elucidate some
complications due to pregnancy such as preeclampsia, or
give a new insight into pathogenesis of autoimmune diseases
such as rheumatoid arthritis, whose clinical manifestation
subsides during pregnancy. Furthermore, it is known at
present that MC retains for a long time after a child delivery
where it occurs both with fetal MC acquired by the woman
during pregnancy and with maternal MC in her descendants.
Investigations of long-term effects of fetal and maternal MC
is a novel, active research, its results indicate both favourable
and unfavourable long-term effects of MC.
The present article is a review of available data on maternal
or, to be more precise, maternal-fetal microchimerism and
described or experimentally proposed its consequences.
Genes & Cells. 2011;6(2):10-14



Derma fibroblasts: peculiarities of cytogenesis, histophysiology and possible clinical use
Abstract
Gaining current experimental data a major concept on
fibroblasts, the main cells of loose and dense connective
tissue, undergoes significant changes moving away off classical
concepts. Considering fibroblasts as a true phenotypic
category we tried to address most challenging issues relating
to definition of a fibroblast differon, cellular sources of their
cytogenesis, histophysiology, their ageing changes in terms of
influence on possible clinical use.
Genes & Cells. 2011;6(2):15-26



Mechanisms of immunomodulatory effects of mesenchymal stem cells
Abstract
Mesenchymal stem cells play different roles in organism
and are capable to differentiate into mesenchymal cells line
(osteoblasts, chondrocytes, adipocytes) and other cell lines.
MSCs also can interact (directly and indirectly) with almost
all cells of immune system via soluble factors and cell-contact
interactions and substantially modulate immune response of
an organism. MSCs can be applied in medical practice as the
safe immunosuppressive agent for allogenic transplantation
and for treatment of autoimmune diseases. This review
deals with interactions between MSCs and immune cells and
mechanisms of MSC-induced immunosuppression.
Genes & Cells. 2011;6(2):27-31



Induced pluripotent stem cells as a model for studying human diseases
Abstract
Induced pluripotent stem cells are able for infinite selfrenewal
and differentiation into all types of cells. The review is
focused on modern methods and approaches to create models
of human diseases based on human induced pluripotent stem
cells, recent advances and prospects in this area, as well
as the application of such models to study human diseases.
Genes & Cells. 2011;6(2):32-37



Personalized cell therapy in ophthalmology. I. Method for obtaining and phenotype of autologous product
Abstract
The method for obtaining activated in vitro by poly A:U
autologous leucocytes from peripheral blood for corneal
diseases treatment is developed. Method allows us to obtain
a product with sufficient content of viable nucleated cells (up
to 3106 cell/ml). Cellular composition of the product was
determined. Mononuclear fraction decreased in 1,3 times and
granulocyte portion is increased. Phenotype of lymphocytes
in the cell product is the same as in peripheral blood, with
selective loss of B-lymphocytes. The presence of CD14+/34low
cells, which are considered to be progenitors, is defined in the
product. Using of cell product, obtained by designed technique,
may be promising in clinic, because of it minimal traumatism
for the patient and simplicity.
Genes & Cells. 2011;6(2):38-42



Dynamics of a growth factors serum level in therapy of myocardial infarction with mesenchymalstem cells in an experiment
Abstract
The aim of the work was to assess TGF в, VEGF-C and
GM-CSF concentrations in the serum of rats after postinfarct
intramyocardial injection of mesenchymal stem cells.
Myocardial infarction was simulated by the criodestruction
of the left ventricular anterior wall. Mesenchymal stem
cells were derived from rat bone marrow and injected into
myocardium 21 days after the crioinjury. The levels of TGF в,
VEGF-C and GM-CSF were measured at 3, 7 and 14 days. The
synthetic activity of the transplanted cells to these growth
factors in vitro was also measured. It was shown that the
administration of mesenchymal cells leads to an increased
level of TGF в in the peripheral blood. The maximum TGF в
concentration was observed on Day 7 after transplantation.
Despite the intensive synthesis of VEGF-C and GM-CSF by
mesenchymal cells in vitro, they do not demonstrate a
significant effect on the level of the studied growth factors in
the peripheral blood.
Genes & Cells. 2011;6(2):43-47



Systems approach to the guarantee of quality of mesenchymal stem cells of bone marrow for the clinical use
Abstract
Mesenchymal stromal/stem cells (MSCs) of bone marrow
(BM) origin not only provide the supportive microenvironmental
niche for hematopoietic stem cells (HSCs) but are also capable
of differentiating into various cell types of mesenchymal
origin, such as bone, fat, and cartilage. The role is known
for bone marrow-derived MSCs in reducing the incidence and
severity of graft-versus host disease (GVHD) during allogeneic
transplantation. Purpose: to estimate quality and biological
safety the MSC of bone marrow for the transplantation.
Were analyzed data expansion MSC of 94 BM at the Stem Cell
Bank of Moscow between 2007 and 2010 on the registered
medical technologies. MSC were revealed in the native form
or frozen in liquid nitrogen. Quality, MSC was evaluated with
of the bacteriological and virusological control; determined
the viability of cells with the trypan blue and 7AAD; markers
that specifically identifies MSCs: CD73+; CD 90+; CD105+;
CD45-; CD34-; CD14; CD133-; CD19-; HLA DR- by flow
cytometry. The biological safety (karyotype) was analyzed by
G-banding technique; 15-30 metaphase cells for each culture
were analyzed. To analyze the level aneuploidy, fluorescent in
situ hybridization (FISH) with chromosome enumeration probes
(CEP) studies was performed. Are developed the documents,
which regulate the stages of the work of expansion MSC of
BM. Were prepared 71 MSC of BM (157 doses) and were
used for allogeneic transplantation 23 to patients (70
doses MSC) for the purpose of adherence HSC, reducing
the incidence and severity of GVHD. In the majority of the
cases of transplantation MSC it was carried out at the
dose of 2 ×106/kg. There were no acute reactions during the
transplantation MSC BM. Thus, the estimation of quality and
safety MSC of BM for allogeneic transplantation, included: a
conducting of documentation on GMP to standards, inspection
of a quantity of cells for achievement of optimum dose,
bacteriological and virusological control, confirmation the
markers that specifically identifies MSCs and the estimation
of biological safety.
Genes & Cells. 2011;6(2):51-54



«Niche - relief» conception for stem cells as a basis of biomimetic approach to boneand hemopoietic tissues engineering
Abstract
An affect of relief features and quantitative parameters
of model mineral matrix on in vitro structure-functional
status of human lung prenatal stromal cells (HLPSC) and
in vivo remodeling of mice bone/marrow system has been
studied. According to data established, rough (Ra > 2 m)
implants with calcium phosphate micro-arc coatings simulate
three-dimensional state of regenerating bone matrix. Such
surfaces have own structure-functional sites (microregions)
which were named by niche - relief and were necessary
for maturation and differentiation of HLPSC to secreting
osteoblasts. Maximum remodeling of mice bone/marrow
system in heterotopic test in vivo was also observed under
optimal parameters of osteogenic niche in vitro (approximately
43% average index of cellular alkaline phosphatase square
to artificial microregion area). A probable cell-molecular
mechanism of influence experimental 3D-modeling of bone
surface on selection of quiescent or active state by endosteal
niche has been detected. It connects with activating cellular
production of bone matrix components (alkaline phosphatase,
osteocalcin, collagen, calcium phosphates) that dissociate
dimensionally stromal and hemopoietic elements, and with
parallel diminishing TNF secretion in intercellular medium.
The data obtained develop our previous speculations about
existence and sizes of artificial endosteal niche for osteogenic
differentiation of multipotent mesenchimal stromal cells.
Genes & Cells. 2011;6(2):55-64



Effects of Н2О2-plasma processing on properties of cellular scaffolds made of «Bioplastotan»resorbing polyesters
Abstract
Produced from «Bioplastotan» resorbing polyesters (linear
polyesters of hydroxyl derivatives alkanoic acids) scaffolds for
cell culturing such as films, pressed 3-D forms and nonwoven
fabric from ultrathin fibers are characterized. Two types of
polymers - a homopolymer of the 3-hydroxybutyric acid and
a copolymer formed by monomers of the 3-hydroxybutyric
and 3-hydroxyvalerianic acids are studied. Surface properties
of developed polymer scaffolds, sterilized with autoclaving
and Н2О2-plasma processing are compared. It is shown that
plasma has beneficial effects resulting in decrease of the
watering contact angle and increase of surface hydrophilic
properties. Positive effects of Н2О2-plasma processing
of scaffold surface on culturing cell adhesion and viability
compared with autoclaving sterilization is demonstrated on
NIH 3T3 line fibroblast culturing.
Genes & Cells. 2011;6(2):65-70



Tsirkuliruyushchie gemopoeticheskie i endotelial'nyepredshestvenniki v perifericheskoy krovi patsientovs cherepno-mozgovoy travmoy
Abstract
В настоящей работе исследована мобилизация ге-
мопоэтических стволовых/прогениторных клеток (ГСК)
и эндотелиальных предшественников (ЭП) у больных с
черепно-мозговой травмой (ЧМТ). В первые 24-48 ч по-
сле ЧМТ выявлено достоверное возрастание абсолютного
количества циркулирующих CD34+CD45+ГСК, а также от-
носительного и абсолютного количества CD34+CD144+ЭП.
Эффективность мобилизации ГСК была достоверно выше
в группе больных до 40 лет, и относительное содержание
CD45+CD34+ клеток находилось в обратной зависимости
от возраста пациентов (r = -0,54, р = 0,039). Возрас-
тание CD45+CD34+ГСК и CD34+CD144+ЭП регистриро-
валось как у больных с легкой, так и среднетяжелой/тя-
желой ЧМТ и не зависело от уровня сознания по шкале
комы Глазго (ШКГ). Однако у больных с отсутствием воз-
растания CD45+CD34+ клеток частота неблагоприятных
исходов (1-3 балла по шкале исходов Глазго; ШИГ) была
достоверно выше, чем в подгруппе больных с повышенным
количеством ГСК (p = 0,047). Выявлена также значимая
взаимосвязь ранних ЭП, не экспрессирующих VE-кадгерин
(CD3-CD34+CD144-ЭП), с тяжестью/исходом ЧМТ (r = 0,6;
p = 0,017 и r = 0,53; p = 0,035, соответственно). Таким
образом, интенсивность мобилизации ГСК и ЭП у больных
ЧМТ может быть использована в качестве прогностического
фактора, свидетельствующего о репаративном потенциале
костномозговых предшественников.
Genes & Cells. 2011;6(2):71-77



Sinusoidal liver cells and bone marrow cells as components of the common functional systemfor regulation of recovery morphogenesis of healthy and damaged liver
Abstract
This review presents current information about the
cooperative interaction of sinusoidal liver cells and bone marrow
cells at the processes of physiological, reparative and fibrosing
liver regeneration. It is shown that the stem / progenitor cells
of bone marrow (hematopoietic and mesenchymal stromal
cells) supplement regulatory role of liver stem cells (first
of all stellate cells - Ito cells), reduce the seriousness of
inflammation and fibrosis, and thereby normalize the recovery
process of damaged liver regeneration. It is believed that the
use of mesenchymal stromal cells of bone marrow is the most
future forward strategy. However, to form a final opinion on
the regenerative capacity of autologous and allogeneic bone
marrow cells at hepatic failure large-scale double-blind clinical
trials should be carried out.
Genes & Cells. 2011;6(2):78-92



A concept of cytoregulation therapy in brain glial tumors: novel theoretical and methodological platformof using cell-based technologies in neuro-oncology
Abstract
Current standard methods of curing patients with brain
tumors targeted to complete elimination of tumor cells from
the body are of low effectiveness. Disappointing results of
generally accepted therapy modalities ordain searching for
novel approaches to treatment with oncopathology, based
on detailed understanding of oncogenesis and interaction of
tumor cells with the body normal ones. In this discussion
article on the basis of the developed hypothesis of induced
bioregulation of tumor cells we have proposed a conceptually
different methodological concept of therapeutic correction
brain tumors - cytoregulatory therapy which is based on using
induced regional multipotent stem cells as the main approach
in the central nervous system tumors.
Genes & Cells. 2011;6(2):93-103



Influence of Autologous Connective Tissue (Stromal) Bone Marrow Cells (SBMC)Upon Delayed-Forming Distraction Regenerates in Children
Abstract
Results of cultivated autologous connective tissue bone
marrow cells use for the stimulation of distraction bone
regenerates in 8 children aged from 3.7 to 16.0 years with
congenital lower extremities length discrepancy (main group)
are compared with those achieved for 24 children aged
2.5-14.0 with similar pathology who were treated without
application of cell technology (control group). Treatment
results are indicative of marked stimulating effect of cell
therapy upon the formation and maturation of distraction
bone regenerates after surgical correction of lower
extremities length discrepancy. In the main group duration
of treatment reduced to 4,5-6,5 months versus 7,5-11
months in the control group. Subsequently with growth of
children the elongated limb segments in children from the
main group showed less delay in development as compared
with elongated limb segments in patients from the control
group. It is obvious that use of SBMC has exerted stimulating
effect upon the growth of the whole segment of the operated
extremity approximating the rates of its development the
physiological ones.
Reduction of treatment duration enabled to avoid potential
complications related to prolonged extremity fixation in
distraction apparatus and to perform rehabilitation at earlier
terms than in patients from the control group that led to the
improvement of anatomical and functional results.
Genes & Cells. 2011;6(2):104-112


