E.D. Gol’dberg
A.M. Dygai
G.N. Zuyz’kov
V.V. Zhdanov |
PHARMACOLOGICAL REGULATION OF FUNCTIONAL ACTIVITY
OF PROGENITOR CELLS |
| Institute of Pharmacology, Tomsk Research Center, Siberian
Division, Russian Academy of Medical Sciences, Tomsk, Russia |
The сell therapy is one of the most perspective directions of modern medicine,
however introduction in the organism of exogenous progenitor cells represents
frequently serious medical, or ethical problem. In our opinion, сonvenient
way of stimulating recovery of different organs and tissues from resident stem
cells seems to be pharmacological activation of their functions. In one’s
turn, the creation of noninvasive methods of cellular therapy isn’t possible
without extending knowledge about regularities of progenitor elements role in
the development and resolution of pathological processes. The aim of this work
was studying the role of mesenchymal progenitor cells of different classes in
the development of pathological processes and perfection of pharmacological
stimulation methods of their mobilization and differentiation in tissue-specific
precursors on the models of some widespread diseases. We observed for functional
and morphological states of damaged organs in mice and rats caused by myocardial
infarction, chronic hepatitis, diabetes mellitus, hypoxic encephalopathy or
injuries of skin and administration of substances, influencing on stem
cells. It was determined the content of multipotent mesenchymal stromal cells
and committed fibroblast precursors in bone marrow and peripheral blood.
Moreover, the number of local precursors in myocardium, liver, pancreas, brain
or region of skin wound was evaluated. It was established, that the development
of pathological processes is accompanied by activation of primitive and more
mature mesenchymal precursors in bone marrow, which is insufficient in
most cases for their mobilization in the peripheral blood or for elimination
of suppressing effects of toxic agents on organs-targets. The stimulation of
stem cells by granulocyte colony stimulating factor (G-CSF) resulted in more
early or more expressed increase of mesenchymal precursors content in bone marrow
and peripheral blood. Also, the number of local precursor-cells in regenerating
parenchymatous organs was raised. At that, regenerating organs showed decreasing
extent of developed conjunctive tissue or infiltration degree and increasing
part of tissue-specific structures. The epithelization of wound on the
model of skin flap was accelerated. It was found, that mobilizing action
of G-CSF is based on weakening of binding capacity of progenitor elements with
microenvironment cells, but not with intercellular matrix. Additional administration
of hyaluronidase to G-CSF enhances mobilizing effect of cytokine in respect
of mesenchymal precursors. Thus, pharmacological activation of progenitor cells
in situ, results in acceleration of reparation of the injured organs at the
expense of regeneration switching from substitution to a tissue-specific
way.
