The probability of a Black African finding a matched unrelated donor for a hematopoietic stem cell transplant is minimal due to the high degree of genetic diversity amongst individuals of African origin. This problem could be resolved in part by the establishment of a public cord blood (CB) stem cell bank. The high prevalence of human immunodeficiency virus (HIV) amongst women attending antenatal clinics in sub-Saharan Africa together with the risk of mother-to-child transmission increases the risk of transplant transmissible infection. In addition to screening the mother in a period inclusive of 7 days prior to the following delivery, we propose that all CB units considered for storage undergo rigorous and reliable screening for HIV. The Ultrio-plus® assay is a highly specific and sensitive test for detecting HIV, hepatitis-B and hepatitis-C viruses in peripheral blood. We validated the Ultrio-plus® assay for analytical sensitivity in detecting HIV in CB at the level of detection of the assay. Until more comprehensive and sensitive methods are developed, the sensitivity and reliability of the Ultrio-plus® assay suggest that it could be used for the routine screening of CB units in conjunction with currently recommended maternal screening to reduce the risk of transplant transmissible infection.

Stem cell therapy has the optimistic goal of regenerating the myocardium as defined by re-growth of lost or destroyed myocardium. As applied to patients with heart failure, many confuse or limit the regenerative definition to just improving myocardial function and/or decreasing myocardial scar formation, which may not be the most important clinical outcome to achieve in this promising field of molecular medicine. Many different stem cell-based therapies have been tested and have demonstrated a safe and feasible profile in adult patients with heart failure, but with varied efficacious end points reported. Although not achieved as of yet, the encompassing goal to regenerate the heart is still believed to be within reach using these cell-based therapies in adult patients with heart failure, as the first-generation therapies are now being tested in different phases of clinical trials. Similar efforts to foster the translation of stem cell therapy to children with heart failure have, however, been limited. In this review, we aim to summarise the findings from pre-clinical models and clinical experiences to date that have focussed on the evaluation of stem cell therapy in children with heart failure. Finally, we present methodological considerations pertinent to the design of a stem cell-based trial for children with heart failure, as they represent a population of patients with very different sets of issues when compared with adult patients. As has been taught by many learned clinicians, children are not small adults!

It was recently reported that in one of the adult neurogenetic zones, the subventricular zone (SVZ), astrocyte-like cells release glutamate upon intracellular Ca2+ increases. However, the signals that control Ca2+ activity and glutamate release from SVZ astrocytes are not known. Here, we examined whether prostaglandin E2 (PGE2), which induces glutamate release from mature astrocytes, is such a signal. Using the gramicidin-perforated patch-clamp technique, we show that the activity of N-Methyl-D-Aspartate receptor (NMDAR) channel in neuroblasts is a high fidelity sensor of ambient glutamate levels. Using such sensors, we found that application of PGE2 led to increased ambient glutamate levels in the SVZ. In parallel experiments, PGE2 induced an increase in intracellular Ca2+ levels in SVZ cells, in particular astrocyte-like cells, as shown using Ca2+ imaging. Finally, a PGE2 enzyme immunoassay showed that the choroid plexus of the lateral ventricle and to a lesser extent the SVZ (ten-fold less) released PGE2. These findings suggest that PGE2 is a physiological signal for inducing glutamate release from SVZ astrocytes that is important for controlling neuroblast survival and proliferation. This signal may be accentuated following ischemia or injury-induced PGE2 release and may contribute to the injury-associated increased neurogenesis.

Solid tumors and hematological cancers contain small population of tumor cells that arebelieved to play a critical role in the development and progression of the disease. Thesecells, named Cancer Stem Cells (CSCs), have been found in leukemia, myeloma, breast,prostate, pancreas, colon, brain and lung cancers. It is also thought that CSCs drive themetastatic spread of cancer. The CSC compartment features a specific and phenotypicallydefined cell population characterized with self-renewal (through mutations), quiescence orslow cycling, overexpression of anti-apoptotic proteins, multidrug resistance and impaireddifferentiation. CSCs show resistance to a number of conventional therapies, and it isbelieved that this explains why it is difficult to completely eradicate the disease andwhy recurrence is an ever-present threat. A hierarchical phenomenological model isproposed based on eight compartments following the stem cell lineage at the normal andcancer cell levels. As an empirical test, the tumor grading and progression, typicallycollected in the pathologic lab, is used to correlate the outcome of this model with thetumor development stages. In addition, the model is able to quantitatively account for thetemporal development of the population of observed cell types. Two types of therapeutictreatment models are considered, with dose-density chemotherapy (a pulsatile scenario) aswell as continuous, metronomic delivery. The drug hit is considered at the stem cellprogenitor and early differentiated specialized cell levels for both normal and cancercells, while the quiescent stem cell and fully differentiated compartments are consideredfavorable outcome for cancer treatment. Circulating progenitors are neglected in thisanalysis. The model provides a number of experimentally testable predictions. The relativeimportance of the cell kill and survival is demonstrated through a deterministicparametric study. The significance of the stem cell compartment is underlined based onthis simulation study. This predictive mathematical model for cancer stem cell hypothesisis used to understand tumor responses to chemotherapeutic agents and judge theefficacy.

Totipotent somatic stem cells (neoblasts) are key players in the biology of flatworms and account for their amazing regenerative capability and developmental plasticity. During recent years, considerable progress has been made in elucidating molecular features of neoblasts from free-living flatworms, whereas their role in parasitic species has so far merely been addressed by descriptive studies. Very recently, however, significant advances have been made in the in vitro culture of neoblasts from the cestode Echinococcus multilocularis. The isolated cells proved capable of generating mature metacestode vesicles under laboratory conditions in a manner that closely resembles the oncosphere-metacestode transition during natural infections. Using the established neoblast cultivation protocols, combined with targeted manipulation of Echinococcus genes by RNA-interference, several fundamental questions of host-dependent parasite development can now be addressed. Here, I give an overview of current cultivation techniques for E. multilocularis neoblasts and present experimental approaches to study their function. Furthermore, I introduce the E. multilocularis genome sequencing project that is presently in an advanced stage. The combined input of data from the E. multilocularis sequencing project, stem cell cultivation, and recently initiated attempts to genetically manipulate Echinococcus will provide an ideal platform for hypothesis-driven research into cestode development in the next years.

Heart failure is a leading cause of death worldwide. Current therapies only delay progression of the cardiac disease or replace the diseased heart with cardiac transplantation. Stem cells represent a recently discovered novel approach to the treatment of cardiac failure that may facilitate the replacement of diseased cardiac tissue and subsequently lead to improved cardiac function and cardiac regeneration.

A stem cell is defined as a cell with the properties of being clonogenic, self-renewing, and multipotent. In response to intercellular signalling or environmental stimuli, stem cells differentiate into cells derived from any of the three primary germ layers: ectoderm, endoderm, and mesoderm, a powerful advantage for regenerative therapies. Meanwhile, a cardiac progenitor cell is a multipotent cell that can differentiate into cells of any of the cardiac lineages, including endothelial cells and cardiomyocytes.

Stem cells can be classified into three categories: (1) adult stem cells, (2) embryonic stem cells, and (3) induced pluripotential cells. Adult stem cells have been identified in numerous organs and tissues in adults, including bone-marrow, skeletal muscle, adipose tissue, and, as was recently discovered, the heart. Embryonic stem cells are derived from the inner cell mass of the blastocyst stage of the developing embryo. Finally through transcriptional reprogramming, somatic cells, such as fibroblasts, can be converted into induced pluripotential cells that resemble embryonic stem cells.

Four classes of stem cells that may lead to cardiac regeneration are: (1) Embryonic stem cells, (2) Bone Marrow derived stem cells, (3) Skeletal myoblasts, and (4) Cardiac stem cells and cardiac progenitor cells. Embryonic stem cells are problematic because of several reasons: (1) the formation of teratomas, (2) potential immunologic cellular rejection, (3) low efficiency of their differentiation into cardiomyocytes, typically 1% in culture, and (4) ethical and political issues. As of now, bone marrow derived stem cells have not been proven to differentiate reproducibly and reliably into cardiomyocytes. Skeletal myoblasts have created in vivo myotubes but have not electrically integrated with the myocardium. Cardiac stem cells and cardiac progenitor cells represent one of the most promising types of cellular therapy for children with cardiac failure.

Oligodendrocyte precursor cells (OPCs) have become the focus of intense research, not only because they generate myelin-forming oligodendrocytes in the normal CNS, but because they may be suitable for transplantation to treat disorders in which myelin does not form or is damaged, and because they have stem-cell-like properties in that they can generate astrocytes and neurons as well as oligodendrocytes. In this article we review the electrical signalling properties of OPCs, including the synaptic inputs they receive and their use of voltage-gated channels to generate action potentials, and we describe experiments attempting to detect output signalling from OPCs. We discuss controversy over the existence of different classes of OPC with different electrical signalling properties, and speculate on the lineage relationship and myelination potential of these different classes of OPC. Finally, we point out that, since OPCs are the main proliferating cell type in the mature brain, the discovery that they can develop into neurons raises the question of whether more neurons are generated in the mature brain from the classical sites of neurogenesis in the subventricular zone of the lateral ventricle and the hippocampal dentate gyrus or from the far more widely distributed OPCs.

Tumor growth and progression is a complex phenomenon dependent on theinteraction of multiple intrinsic and extrinsic factors. Necessary for tumordevelopment is a small subpopulation of potent cells, so-called cancer stemcells, that can undergo an unlimited number of cell divisions and which areproposed to divide symmetrically with a small probability to produce more cancerstem cells. We show that the majority of cells in a tumor must indeed benon-stem cancer cells with limited life span and limited replicative potential. Tumor development is dependent as well on the proliferative potential and deathof these cells, and on the migratory ability of all cancer cells. Withincreasing number of cells in the tumor, competition for space limits tumorprogression, and in agreement with in vitro observation, the majority of cancercells become quiescent, with proliferation primarily occurring on the outer rimwhere space is available. We present an agent-based model of early tumordevelopment that captures the spatial heterogeneity of stemness andproliferation status. We apply the model to simulations of radiotherapy topredict treatment outcomes for tumors with different stem cell pool sizes anddifferent quiescence radiosensitivities. We show by first presuming homogeneousradiosensitivity throughout the tumor, and then considering the greaterresistance of quiescent cells, that stem cell pool size and stem cellrepopulation during treatment determine treatment success. The results fortumor cure probabilities comprise upper bounds, as there is evidence that cancerstem cells are also more radioresistant than other tumor cells. Beyond justdemonstrating the influence of mass effects of stem to non-stem cell ratios andproliferating to quiescent cell ratios, we show that the spatiotemporalevolution of the developing heterogeneous population plays a pivotal role indetermining radioresponse and treatment optimization.

Objective: To investigate the location of the scala media in relation to the round window niche in human temporal bones.

Design: Ten human temporal bones were investigated by radical mastoidectomy and promontory drill-out.

Setting: Temporal bone laboratory.

Outcome measures: The distance from the scala media to the anterior edge of the round window niche, measured by Fisch's stapedectomy measuring cylinders.

Results: The scala media was identified at the transection point of a vertical line 1.6 to 2.2 mm (mean=1.8 mm; standard deviation=0.2) anterior to the anterior edge of the round window niche and a horizontal line 0.2 mm inferior to the lower border of the oval window.

Conclusion: This report demonstrates the point of entry into the scala media via the promontory in fixed temporal bone models, which may provide a site of entry for stem cells and gene therapy insertion.

Tissue-specific stem cells play a key role in organ homoeostasis. They are relatively well characterized in systems which undergo constant proliferation and production of differentiated cells, including the haemopoietic system, skin and intestine. However, little is known about the role and regulation of stem cells in the mammary gland. This review briefly summarizes the current understanding of the role of breast-specific stem cells in normal and cancerous tissues, and how this may identify new targets for breast cancer prevention and therapy.