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     

Eustress and Distress: Neither Good Nor Bad,but Rather the Same?

The terms “eustress” and “distress” are widely used throughout the scientific literature. As of February 2020, 203 items in the Web of Science show up in a search for “eustress,” however, there are almost 16 400 items found in a search for the term “distress.” Based on the reasoning in this article, however, it is believed there is no such thing as eustress or distress. The adaptation reaction of an organism under stress is not intrinsically good or bad, and its effect on health or performance depends on a plethora of other interactions of the body with the environment as well as on the history of such interactions. The vagueness of the terms “eustress/distress” has historically led to vast differences in the perception and application of the terms across disciplines. While psychology or sociology perceive eustress as something inextricably linked to positive perception and enhanced cognition, biomedicine perceives eustress as generally associated with better survival, health, or increased longevity, no matter how the event is perceived. In this paper, the authors review the current understanding of the term “eustress” in different fields, discuss possible implications of its misleading use, and suggest that the term may be replaced by “stress” only.     

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.     

Amyloid β Peptides Promote Autophagy-Dependent Differentiation of Mouse Neural Stem Cells

Although regarded as neurotoxic, amyloid β (Aβ) peptides may also mediate a wide range of nonpathogenic processes. Autophagy has been implicated in Aβ-mediated effects, although its precise function in neural differentiation remains unknown. Here, we addressed the role of different Aβ fragments in neural stem cell (NSC) proliferation and differentiation, and investigated whether autophagy is involved in Aβ-induced alterations of neural fate. Our results demonstrate that neuronal and glial-specific protein markers are significantly induced by both Aβ_1–40 and Aβ_1–42. However, Aβ_1–40 preferentially enhances neurogenesis of NSCs, as determined by βIII-tubulin, NeuN, and MAP2 neuronal marker immunoreactivity, while Aβ_1–42 appears to favor gliogenesis. In contrast, Aβ_25–35 does not influence NSC fate. The effect of Aβ_1–40 on neurogenesis is partially dependent on its role in NSC self-renewal as both S-phase of the cell cycle and BrdU labeling were markedly increased. Nevertheless, Aβ_1–40 resulted also in increased Tuj1 promoter activity. Autophagy, assessed by conversion of endogenous LC3-I/II, fluorescence of pGFP-LC3-transfected cells, and Atg9 protein levels, was evident in both Aβ_1–40- and Aβ_1–42-treated NSCs, independently of reactive oxygen species production and apoptosis. Finally, inhibition of autophagy by pharmacologic means abrogated Aβ-induced lineage-specific protein markers. These results support distinct roles for different Aβ peptides in NSC fate decision and underline the importance of autophagy control of this process.     

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.     

Breast Tumor Heterogeneity: Cancer Stem Cells or Clonal Evolution?

Breast tumors are composed of a variety of cell types with distinct morphologies and behaviors. It is not clear how this tumor heterogeneity comes about. Two popular concepts that attempt to explain this are the cancer stem cell hypothesis and the clonal evolution model. Each of these ideas has been investigated for some time, leading to the accumulation of numerous findings that are used to support one or the other. Although the two views share some similarities, they are fundamentally different notions with very different clinical implications. Analysis of the research backing each concept, along with a review of the results of our recent study investigating putative breast cancer stem cells, suggests how the cancer stem cell hypothesis and the clonal evolution model may be involved in generating breast tumor heterogeneity. An understanding of this process will allow the development of more effective ways to treat and prevent breast cancer.     

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.