Inhibition of GSK3 promotes replication and survival of pancreatic beta cells.

Recent developments indicate that the regeneration of beta cell function and mass in patients with diabetes is possible. A regenerative approach may represent an alternative treatment option relative to current diabetes therapies that fail to provide optimal glycemic control. Here we report that the inactivation of GSK3 by small molecule inhibitors or RNA interference stimulates replication of INS-1E rat insulinoma cells.

In vivo haematopoietic activity is induced in neurosphere cells by chromatin-modifying agents.

Modifications of DNA and chromatin are fundamental for the establishment and maintenance of cell type-specific gene expression patterns that constitute cellular identities. To test whether the developmental potential of fetal brain-derived cells that form floating sphere colonies (neurospheres) can be modified by destabilizing their epigenotype, neurosphere cells were treated with chemical compounds that alter the acetylation and methylation patterns of chromatin and DNA. Intravenous infusion of bulk or clonally derived neurosphere cells treated with a combination of trichostatin A (TSA) plus 5-aza-2'-deoxycytidine (AzaC) (TSA/AzaC neurosphere cells) yielded long-term, multilineage and transplantable neurosphere-derived haematopoietic repopulation.

Erythroid-like cells from neural stem cells injected into blastocysts.

Objective: In contrast to embryonic stem (ES) cells, which are able to give rise to all cell types of the body, somatic stem cells have been thought to be more limited in their differentiation potential in that they are committed to generate only cells of their tissue of origin. Unexpectedly, some recent data suggest that somatic stem cells isolated from one tissue can also generate cells of heterologous tissues and organs, implying that somatic stem cells have a greater potential for differentiation.

Methods: To explore further the developmental potential of murine neural stem cells (NSCs) we injected cultured NSCs as neurospheres into preimplantation blastocysts and determined the seeding by donor cells in tissues of developing chimeric fetal and adult animals.

Chimaerism and erythroid marker expression after microinjection of human acute myeloid leukaemia cells into murine blastocysts.

It has been suggested that the embryonic microenvironment can control the survival and the transformed phenotype of tumour cells. Here, we addressed the hypothesis that the murine embryonic microenvironment can induce the differentiation of human tumour cells. To examine such interactions, we injected human leukaemic cells into preimplantation murine blastocysts at embryonic day 3.

Plasticity of hematopoietic stem cells and cellular memory.

Stem cell systems represent an effective and powerful approach for tissue development and regeneration of diverse tissue types. Common and defining features of these exceptional cells are the capacity for self-renewal and the potential for differentiation into multiple mature cell types. Recently, surprising new observations have indicated that stem cells isolated from one adult tissue can also give rise to mature cells of other cell lineages, irrespective of classical germ layer designations.

Developmental potential of hematopoietic and neural stem cells: unique or all the same?

Like many other animals, mammals develop from fertilized oocytes - the ultimate stem cells. As embryogenesis proceeds, most cells lose developmental potential and eventually become restricted to a specific cell lineage. The result is the formation of a complete and structured mature organism with complex organs composed of a great variety of mature, mostly mitotically quiescent effector cells.

Human hematopoiesis in murine embryos after injecting human cord blood-derived hematopoietic stem cells into murine blastocysts.

At different developmental stages, candidate human hematopoietic stem cells (HSCs) are present within the CD34+ CD38- population. By means of xenotransplantation, such CD34+CD38- cells were recently shown to engraft the hematopoietic system of fetal sheep and nonobese diabetic severe combined immunodeficient adult mice. Here it is demonstrated that, after their injection into murine blastocysts, human cord blood (CB)-derived CD34+ and CD34+ CD38- cells repopulate the hematopoietic tissues of nonimmunocompromised murine embryos and that human donor contribution can persist to adulthood.