Minimal criteria for defining multipotent mesenchymal stromal cells. The International Society for Cellular Therapy position statement

Human mesenchymal stem cells modulate allogeneic immune cell responses

https://sites.bu.edu/chenlab/files/2014/01/38_McBeathDevCell_04.pdf

Cell shape, cytoskeletal tension, and rhoa regulate stem cell lineage commitment

https://www.pure.ed.ac.uk/ws/files/14186931/A_Perivascular_Origin_for_Mesenchymal_Stem_Cells_in_Multiple_Human_Organs.pdf

A perivascular origin for mesenchymal stem cells in multiple human organs

Mesenchymal stem cells (MSCs) are a heterogeneous subset of stromal stem cells that can be isolated from many adult tissues. They can differentiate into cells of the mesodermal lineage, such as adipocytes, osteocytes and chondrocytes, as well as cells of other embryonic lineages. MSCs can interact with cells of both the innate and adaptive immune systems, leading to the modulation of several effector functions. After in vivo administration, MSCs induce peripheral tolerance and migrate to injured tissues, where they can inhibit the release of pro-inflammatory cytokines and promote the survival of damaged cells. This Review discusses the targets and mechanisms of MSC-mediated immunomodulation and the possible translation of MSCs to new therapeutic approaches.

Mesenchymal stem cells in health and disease

Institute of Biological Medicine, Moscow The formation of the concept of a mesenchymal stem cell (MSC) is a priority of Russian biological science. A. Ya. Fridenshtein and his colleagues were the first who experimentally proved the existence of MSC. Osteogenic potential of fibroblastlike bone marrow cells of different mammalian species was demonstrated [25,26]. Fibroblast-like bone marrow cells often formed discrete adhesive colonies in vitro [27,28,47]. After heteroand orthotopic transplantation in vivo cloned cells from these colonies formed bone, cartilaginous, fibrous, and adipose tissues [48]. Intensive self-renewal and multipotency of fibroblast-like colony-forming cells from the bone marrow allowed Fridenshtein and Owen to formulate a concept of multipotent mesenchymal precursor cells (MPC) [62]. An ordered chain of finely regulated cell proliferation, migration, differentiation, and maturation processes underlies the formation of the majority of cell lineages in adult organisms. The earliest cell elements in this chain are stem cells (SC). Along with extensive self-renewal capacity, SC possess a great differentiation potential. Apart from well studied hemopoietic and intestinal SC, other SC classes were recently discovered in adult organism. Until recently it was considered that SC in adults can give rise to cell lines specific to tissues where these cells are located; however, new facts necessitated revision of this concept. Hemopoietic SC capable of differentiating into all cell elements of the blood, can also be a source of hepatic oval cells [65]; neural SC, precursors of neurons and glia [2,3], serve as the source of early and committed hemopoietic precursors [10]. MSC, a source of bone, cartilaginous, and adipose tissue cells, can differentiate into neural cells [46]. Tissue growth and reparation are associated with migration of uncommitted precursor cells from other tissues. During muscle tissue reparation mesenchymal SC migrate from the bone marrow into skeletal muscles [24]. Hence, in addition to capacity to unlimited division and reproduction of a wide spectrum of descendants of a certain differentiation line, adult SC are characterized by high plasticity. The existence of a rare type of somatic pluripotent SC, common precursors of all SC in an adult organism, is hypothesized [79]. Another important characteristic of SC is their migration from the tissue niche into circulation, which was experimentally proven for hemopoietic and MSC [69,73]. For activation of the differentiation program, circulating SC should get into an appropriate microenvironment [75,78]. A potent stimulus for investigation of SC is the possibility of their clinical use in cell and gene therapy. The bone marrow contains multipotent MSC, which can be easily isolated and cultured in vitro. It is therefore interesting to analyze some fundamental aspects of MSC biology and the possibilities of their clinical use. MSC descendants are involved in the formation of bones, cartilages, tendons, adipose and muscle tissues, and stroma maintaining the hemopoiesis [12,19,51]. The term MPC is used to denote MSC and their committed descendants capable of differentiating into at least two types of mature cells, which are present in the bone marrow and some mesenchymal tissues [16,19,57,82].

Mesenchymal Stem Cells

Inbred animals serve as an adequate model to study the role of genetic factors in adaptive, disadaptive, and pathological processes. Morphofunctional study of the immune system was performed on intact BALB/c and C57Bl/6 mice. The structural and functional parameters of the immune system in BALB/c and C57Bl/6 mice differ under physiological conditions. In BALB/c mice, volume density of T zone in the spleen and production of IL-2, IL-3, IL-4, IL-10, and TNF-α were much higher than in C57Bl/6 mice. However, IL-12 production in BALB/c mice was lower than in C57Bl/6 mice. C57Bl/6 mice were characterized by higher cytostatic activity of splenic NK cells. The observed interstrain differences are genetically determined and contribute to the type of adaptive processes and different sensitivity of these mice to pathogenic agents.

Morphofunctional characteristic of the immune system in BALB/c and C57BL/6 mice.

We analyzed the possibility of using fetal stem and progenitor cells for the treatment of various pathologies. A comparative characteristic of stem cells from fetuses and adult donors is presented and advantages of the use of fetal biometerial for biotransplantation are described. The main tissue sources of fetal stem cells are characterized and experimental and clinical data on the use of fetal cells for cytotherapy are presented.

Application potential of human fetal stem/progenitor cells in cell therapy.

Heat shock proteins (HSPs) are the most conserved proteins present in the archea, pro- and eukaryotes HSPs have a dual function depending on their intra- or extracellular location Intracellular HSPs play a cytoprotective role providing the cells with mechanisms to prevent damage caused by misfolded, damaged, aggregated, or insoluble proteins Extracellularly located or membrane-bond HSPs participate in both innate and adaptive immune responses The recent review focuses on the role of HSPs in the pathogenesis of infections, autoimmune, cardiovascular, oncological, neurodegenerative, and other diseases HSPs may serve as potential molecular targets for therapeutic intervention in the treatment of various diseases, including cancer, Alzheimer's and Parkinson's diseases Some HSPs may be used as immunoadjuvants or as HSP-based vaccines for the treatment of infections and cancers

Heat shock proteins and their role in the development of pathological processes

The time course of morphofunctional changes in the liver, thymus, and spleen was observed in BALB/c mice with Con A-induced experimental hepatitis. The progress of alterative changes in the liver was paralleled by intensification of accidental involution of the thymus. On day 1 of hepatitis development high proliferative and cytostatic activity of splenocytes was paralleled by hemorrhagic necroses and depletion of the periarteriolar lymphoid sheaths in the spleen (T-zones), presumably due to migration of activated lymphocytes to the liver and barrier tissues. Later normalization of lymphocyte proliferative activity was paralleled by recovery and hyperplasia of the splenic T-cell zones.

Bogdanova Im

Papers

Mesenchymal Stem Cells

Morphofunctional characteristic of the immune system in BALB/c and C57BL/6 mice.

Application potential of human fetal stem/progenitor cells in cell therapy.

Heat shock proteins and their role in the development of pathological processes

Dynamics of morphofunctional changes in immune organs of BALB/c mice with experimental hepatitis.