LifeMap Discovery?: The Embryonic Development,Stem Cells,and Regenerative Medicine Research Portal

LifeMap Discovery™ provides investigators with an integrated database of embryonic development, stem cell biology and regenerative medicine. The hand-curated reconstruction of cell ontology with stem cell biology; including molecular, cellular, anatomical and disease-related information, provides efficient and easy-to-use, searchable research tools. The database collates in vivo and in vitro gene expression and guides translation from in vitro data to the clinical utility, and thus can be utilized as a powerful tool for research and discovery in stem cell biology, developmental biology, disease mechanisms and therapeutic discovery. LifeMap Discovery is freely available to academic nonprofit institutions at http://discovery.lifemapsc.com     

Are Human and Mouse Satellite Cells Really the Same?

Satellite cells are quiescent cells located under the basal lamina of skeletal muscle fibers that contribute to muscle growth, maintenance, repair, and regeneration. Mouse satellite cells have been shown to be muscle stem cells that are able to regenerate muscle fibers and self-renew. As human skeletal muscle is also able to regenerate following injury, we assume that the human satellite cell is, like its murine equivalent, a muscle stem cell. In this review, we compare human and mouse satellite cells and highlight their similarities and differences. We discuss gaps in our knowledge of human satellite cells, compared with that of mouse satellite cells, and suggest ways in which we may advance studies on human satellite cells, particularly by finding new markers and attempting to re-create the human satellite cell niche in vitro. (J Histochem Cytochem 58:941–955, 2010)     

Erectile Dysfunction and Essential Hypertension: The Same Aging-related Disorder?

An erection is a mechanical event dependent primarily on corporeal vascular dynamics wherein arterial inflow and storage of blood within the corpora is greater than the egress of blood from the corpora. The most common cause of erectile dysfunction (ED) is the inability of the corporal tissue to store the blood within the corporal sinusoids once inflow into the corpora begins. This failure to store is primarily due to a corporal smooth muscle dysfunction and, in most men, is most likely an aging-related occurrence. Because the corporal smooth muscle is embryologically and physiologically indistinguishable from the smooth muscle within our arterial system, the authors hypothesize that the aging-related dysfunction that occurs within the penis also occurs within the arterial system, and that this smooth muscle dysfunction within the arterial media is most likely the cause of what is called essential hypertension. This panvascular smooth muscle myopathy could explain why hypertension is the most common comorbidity associated with ED and appears to indicate that both ED and essential hypertension are the same disorder, albeit in two different organ systems.Key words: Erection, Endothelium, Smooth muscle, HypertensionAlmost all men recognize at some time in their lives that their erectile function begins to change. For most men, the ability to attain and maintain an erection during the teenage years is second nature. However, by the time men hit the fourth and fifth decade of life, many have recognized that their erectile function has changed, and the ability to maintain an erection during sex has diminished; the refractory period, the time in between erectile events, begins to increase. Although men in their teenage years and young adult lives are able to have multiple erectile events at will, this ability begins to fade as aging sets in. Because the ability to maintain an erection is directly related to the function of the corporal smooth muscle, this increase in the refractory period is a clinical sign that the smooth muscle of the corpora is likely becoming dysfunctional. This review highlights what we know about the corporal smooth muscle cell and demonstrates that what occurs to the corporal smooth muscle cell also occurs to its embryologic sibling, the smooth muscle cell within the media of the peripheral vascular system. As a result of this relationship, changes in the function of the penis can reflect changes in the vascular system.     

The Missing Niche for Spermatogonial Stem Cells: Do Blood Vessels Point the Way?

Although spermatogonial stem cell niches have been defined in lower organisms, their definitive localization in mammalian seminiferous tubules has been elusive. In a recent Science paper, Yoshida et al. (2007) elegantly demonstrated a vascular and interstitial tissue-associated niche for undifferentiated spermatogonia in the mouse.     

Mobilizing Endogenous Stem Cells for Repair and Regeneration: Are We There Yet?

Harnessing endogenous repair mechanisms to promote tissue regeneration in situations in which it does not normally occur has long been a goal in biomedical science. Recent advances in tissue stem cells indicate that this goal may now be achievable. Here we consider both the promise and the hurdles we still have to overcome.     

Hematopoietic Stem Cells in Neonates: Any Differences between Very Preterm and Term Neonates?

Background

In the last decades, human full-term cord blood was extensively investigated as a potential source of hematopoietic stem and progenitor cells (HSPCs). Despite the growing interest of regenerative therapies in preterm neonates, only little is known about the biological function of HSPCs from early preterm neonates under different perinatal conditions. Therefore, we investigated the concentration, the clonogenic capacity and the influence of obstetric/perinatal complications and maternal history on HSPC subsets in preterm and term cord blood.

Methods

CD34+ HSPC subsets in UCB of 30 preterm and 30 term infants were evaluated by flow cytometry. Clonogenic assays suitable for detection of the proliferative potential of HSPCs were conducted. Furthermore, we analyzed the clonogenic potential of isolated HSPCs according to the stem cell marker CD133 and aldehyde dehydrogenase (ALDH) activity.

Results

Preterm cord blood contained a significantly higher concentration of circulating CD34+ HSPCs, especially primitive progenitors, than term cord blood. The clonogenic capacity of HSPCs was enhanced in preterm cord blood. Using univariate analysis, the number and clonogenic potential of circulating UCB HSPCs was influenced by gestational age, birth weight and maternal age. Multivariate analysis showed that main factors that significantly influenced the HSPC count were maternal age, gestational age and white blood cell count. Further, only gestational age significantly influenced the clonogenic potential of UCB HSPCs. Finally, isolated CD34+/CD133+, CD34+/CD133– and ALDH^high HSPC obtained from preterm cord blood showed a significantly higher clonogenic potential compared to term cord blood.

Conclusion

We demonstrate that preterm cord blood exhibits a higher HSPC concentration and increased clonogenic capacity compared to term neonates. These data may imply an emerging use of HSPCs in autologous stem cell therapy in preterm neonates.     

The neuronal ceroid lipofuscinoses: the same, but different?

The NCLs (neuronal ceroid lipofuscinoses) (also known as Batten disease) are a group of at least ten fatal inherited storage disorders. Despite the identification of many of the disease-causing genes, very little is known about the underlying disease mechanisms. However, now that we have mouse or large-animal models for most forms of NCL, we can investigate pathogenesis and compare what happens in the brain in different types of the disease. Broadly similar neuropathological themes have emerged, including the highly selective nature of neuron loss, early effects upon the presynaptic compartment, together with an early and localized glial activation. These events are especially pronounced within the thalamocortical system, but it is clear that where and when they occur varies markedly between different forms of NCL. It is now becoming apparent that, despite having pathological endpoints that resemble one another, these are reached by a sequence of events that is specific to each subtype of NCL.     

The ethics of functional genomics: same, same, but different?

Respect for human life--a notion of worth uniting all members of the human race--constitutes a sense of anthropocentrism that has long been the justification for the enrollment of animals in experimentation executed to develop therapies to alleviate human suffering. Currently, however, advances in functional genomics are causing a qualitative transformation of the rationale for medical research performed on animals. The notion of human distinctness is being fundamentally challenged when gene sequences similar to those found in humans are identified in different species. In this Opinion article, we would like to highlight an inherent tension brought about by the current developments in functional genomics: a tension between the scientific and the ethical status of gene sequences. Is it reasonable to argue that they are the same for all practical purposes but different in ethical status?     

Stem cells: The root of prostate cancer?

The cancer stem cell (CSC) model states that tumors contain a reservoir of self-renewing cells that maintain the heterogeneous cell population of the tumor. These cells appear to be resistant to therapy and can therefore survive to repopulate the tumor during progression to therapy resistant disease. The biology of CSCs is still not definitive since it is difficult to isolate them from solid tumors and analyze their characteristics in vitro. Another challenge is to correlate these characteristics with tumor development and progression in vivo. Using the prostate CSC as a model, this review presents the CSC hypothesis, reviews the origin, identification and functions of prostate CSCs, and discusses the clinical implications and therapeutic challenges CSCs have for cancer therapy.     

Ciliary and Nuclear Transport: Different Places,Similar Routes?

Cilia and flagella are membrane-sheathed, microtubule-based protrusions that decorate the surface of many eukaryotic cells. At their base, they form a selective barrier that concentrates certain proteins within the cilia but excludes others. Kee et al. (2012) now propose that nuclear pore complex proteins form a fundamental part of this diffusion barrier.     

Are Hematopoietic Stem Cells Generated in the Placenta?

In this issue of Cell Stem Cell, the origin of multipotent hematopoietic cells present in the placenta has been assessed in Ncx1(-/-) embryos lacking a functional heart and circulation. Rhodes and colleagues (Rhodes et al., 2008) found lymphoid progenitors in the placenta, as well as in dorsal aorta and yolk sac and vitelline vessels, indicating that they arose in situ.