[Quo vadis hematology?] / Quo vadis, hematológia?

For decades, developing hematopoietic cells have been strictly compartmentalized into a small population of multipotent self-renewing hematopoietic stem cells, multipotent hematopoietic progenitor cells that are undergoing commitment to myeloid or lymphoid fates, and unipotent precursor cells that mature towards peripheral blood and immune cells. Recent studies, however, have provided a battery of findings that cannot be explained by this "classical" hierarchical model for the architecture of hematopoiesis. It is emerging that heterogeneous hematopoietic stem cell populations in the bone marrow coexist, each with distinct, preprogrammed differentiation and proliferation behaviors. Three subsets can be distinguished among them: myeloid-biased (α), balanced (ß), and lymphoid-biased (γ/δ) hematopoietic stem cells. The ratio of these hematopoietic stem cell subsets is developmentally regulated in the foetal liver and hematopoietic stem cells adult bone marrow, and coordinately gives rise to hematopoiesis. Beta- and γ/δ-hematopoietic stem cells are found predominantly early in the life of an organism, whereas α-hematopoietic stem cells accumulate in aged mice and humans. In addition, new sophisticated genetic experiments in mice have identified a major role of long-lived, committed progenitor cells downstream from hematopoietic stem cells as drivers of normal adult hematopoiesis, and revealed that post-transplantation hematopoiesis differs qualitatively and quantitatively from normal steady-state hematopoiesis. These findings have important implications for understanding in situ the regulation of haematopoiesis in health and disease. Orv. Hetil., 2016, 157(46), 1819-1829.

[At the border of pluri- and multipotency: the neural crest stem cells]. / A pluri- és multipotencia határán: a ganglionléc ossejtjei.

The neural crest is a transient, multipotent, migratory cell population that is unique to vertebrate embryos and gives rise to many derivatives, ranging from the neuronal and glial components of the peripheral nervous system to the ectomesenchymal derivatives of the craniofacial area and pigment cells in the skin. Intriguingly, the neural crest derived stem cells are not only present in the embryonic neural crest, but also in their target tissues in the fetus and adult. These postmigratory stem cells, at least partially, resemble their multipotency. Moreover, fully differentiated neural crest-derived cells such as Schwann cells and melanocytes are able to dedifferentiate into stem-like progenitors. Here the authors review current understanding of this unique plasticity and its potential application in stem cell biology as well as in regenerative medicine.

[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.

[Stem cell therapy for diabetes mellitus: progress, prospects and challenges]. / A diabetes mellitus ossejtterápiája: eredmények, lehetoségek s kérdojelek.

Curative therapy for diabetes mellitus mainly implies replacement of missing insulin-producing pancreatic beta cells, with pancreas or islet-cell transplants. The limited supply currently available from cadaveric donor islets for transplantation, however, determines that researchers must explore alternative sources of graft material. Stem cells represent a promising solution to this problem, and current research is being aimed at the creation of islet-endocrine tissue from these undifferentiated cells. Both embryonic stem cells (derived from the inner cell mass of a blastocyst) and adult tissue stem cells (found in the postnatal organism) have been used to generate surrogate beta cells or otherwise restore beta cell functioning. Nevertheless, cell replacement therapies that are stem cell based will remain fiction rather than fact until we can efficiently and reproducibly ensure that stable, fully functional cells can be generated in vitro. It is also critical to ensure that any surrogate or regenerated beta cells have perfectly regulated insulin production, which is essential for physiological glucose homeostasis. As in every emerging field in biology, early reports seem confusing and conflicting. Therefore, discrepancies between different results need to be reconciled. In addition, encouraging studies in rodent models may ultimately set the stage for large-animal studies. In this review, the authors provide insight into research efforts to overcome existing hurdles for this promising therapy.