A novel cyclic RGD-containing peptide polymer improves serum-free adhesion of adipose tissue-derived mesenchymal stem cells to bone implant surfaces.

Seeding of bone implants with mesenchymal stem cells (MSCs) may promote osseointegration and bone regeneration. However, implant material surfaces, such as titanium or bovine bone mineral, fail to support rapid and efficient attachment of MSCs, especially under serum-free conditions that may be desirable when human applications or tightly controlled experiments are envisioned. Here we demonstrate that a branched poly[Lys(Ser(i)-DL-Ala(m))] polymer functionalized with cyclic arginyl-glycyl-aspartate, when immobilized by simple adsorption to tissue culture plastic, surgical titanium alloy (Ti6Al4V), or Bio-Oss(®) bovine bone substitute, significantly accelerates serum-free adhesion and enhances seeding efficiency of human adipose tissue-derived MSCs. Moreover, when exposed to serum-containing osteogenic medium, MSCs survived and differentiated on the peptide-coated scaffolds. In summary, the presented novel polypeptide conjugate can be conveniently used for coating various surfaces, and may find applications whenever quick and efficient seeding of MSCs is required to various scaffolds in the absence of serum.

[Beyond genetics--the emerging role of epigenetics and its clinical aspects]. / A genetikán is túl - Az epigenetika eloretörése és orvosi vonatkozásai.

Analysis of genomic sequences has clearly shown that the genomic differences among species do not explain the diversity of life. The genetic code itself serves as only a part of the dynamic complexity that results in the temporal and spatial changes in cell phenotypes during development. It has been concluded that the phenotype of a cell and of the organism as a whole is more influenced by environmentally-induced changes in gene activity than had been previously thought. The emerging field of epigenetics focuses on molecular marks on chromatin; called the epigenome, which serve as transmitters between the genome and the environment. These changes not only persist through multiple cell division cycles, but may also endure for multiple generations. Irregular alterations of the epigenome; called epimutations, may have a decisive role in the etiology of human pathologies such as malignancies and other complex human diseases. Epigenetics can provide the missing link between genetics, disease and the environment. Therefore, this field may have an increasing impact on future drug design and serve as a basis for new therapeutic/preventative approaches.

Positional identity of murine mesenchymal stem cells resident in different organs is determined in the postsegmentation mesoderm.

Although mesenchymal stem cells (MSCs) of distinct tissue origin have a large number of similarities and differences, it has not been determined so far whether tissue-resident MSCs are the progenies of one ancestor cell lineage or the results of parallel cell developmental events. Here we compared the expression levels of 177 genes in murine MSCs derived from adult and juvenile bone marrow and adult adipose tissue, as well as juvenile spleen, thymus, and aorta wall by quantitative real-time polymerase chain reaction and the results were partially validated at protein level. All MSC lines uniformly expressed a large set of genes including well-known mesenchymal markers, such as α-smooth muscle actin, collagen type I α-chain, GATA6, Mohawk, and vimentin. In contrast, pluripotency genes and the early mesodermal marker T-gene were not expressed. On the other hand, different MSC lines consistently expressed distinct patterns of Hox genes determining the positional identity of a given cell population. Moreover, MSCs of different origin expressed a few other transcription factors also reflecting their topological identity and so the body segment or organ to which they normally contributed in vivo: (1) thymus-derived cells specifically expressed Tbx5 and Pitx2; (2) spleen-derived MSCs were characterized with Tlx1 and Nkx2.5; (3) Pitx1 designated femoral bone marrow cells and (4) En2 appeared in aorta wall-derived MSCs. Thus, MSCs exhibited topographic identity and memory even after long-term cultivation in vitro. On the basis of these results, we suggest that postnatal MSCs isolated from different anatomical sites descend from precursor cells developing in the postsegmentation mesoderm.

Identical, similar or different? Learning about immunomodulatory function of mesenchymal stem cells isolated from various mouse tissues: bone marrow, spleen, thymus and aorta wall.

Mesenchymal stem or multipotent stromal cells (MSCs) have been implicated in tissue maintenance and repair and regulating immune effector cells through different mechanisms. These functions in mouse were primarily described for bone marrow (BM)-derived MSCs. To learn more about MSCs of different tissue origin, we compared the immunophenotype, differentiation ability to adipocyte and bone and immunomodulatory activity of MSCs isolated from BM, spleen, thymus and aorta wall of 14-day-old C57Bl/6 mice. The established cell lines fulfilled the requirements described for MSCs in terms of morphology, surface marker expression and differentiation potential although they were distinguishable regarding the expression pattern of the MSC markers and ability generating other cell types. Most importantly, a remarkable diversity was shown in the capacity of inhibition of mitogen- and alloantigen-induced T-cell proliferation, since BM- and spleen-derived MSCs were the most powerful aorta-derived MSCs were less effective, whereas thymus-derived mesenchymal cells were unable to block T-cell growth in vitro. Accordingly, BM, spleen and aorta, but not thymus-derived MSCs, in combination with BM hematopoietic cells were equally efficient to prevent streptozotocin-induced diabetes in vivo. These findings suggested that MSCs residing in different organs might stem from common ancestor; however, once populating into a given tissue microenvironment, they acquire specific properties mainly in the term of the immunoregulatory function.