StemCellGateway

Stem Cell Reviews and Reports: Non-Genetic Modulation of Notch Activity by Artificial Delivery of Notch Intracellular Domain into Neural Stem Cells

Haupt; Borghese; Brüstle; Edenhofer — 2012-01-31

Type: Original Paper

Stem cells have become a major focus of scientific interest as a potential source of somatic cell types for biomedical applications. Understanding and controlling the elicitors and mechanisms in differentiation of pluripotent stem cell-derived somatic cell types remains a key challenge. The major types of molecular processes that control cellular differentiation involve evolutionary conserved cell signaling pathways. Notch receptors participate in a wide variety of biological processes, including cell fate decisions of stem cells. This study explores the potential of protein transduction to directly deliver recombinant Notch-1 intracellular domain (NICD) into mammalian cells in order to accomplish transgene-free Notch activation. We engineered a cell-permeant version of NICD and explored its function on mouse and human neural stem cells. We show that NICD transduction modulates known direct and indirect Notch target genes and antagonizes the DAPT-mediated inhibition of Notch signaling on the transcriptional level. Moreover, NICD enhances cell proliferation accompanied by increased cyclin D1 and decreased p27 protein levels. In the absence of growth factors NICD strongly impairs neuronal differentiation while being insufficient to keep cells in a proliferative state. Furthermore, our studies depict NICD protein transduction as a novel tool for a time and dose-dependent non-genetic modulation of Notch signaling to decipher its cellular functions.

Stem Cell Reviews and Reports: Ontogeny and Homeostasis of Adult Epithelial Skin Stem Cells

Tumbar — 2012-01-31

Type: Original Paper

Mouse epithelial skin stem cells constitute an important model system for understanding the dynamics of stem cell emergence and behavior in an intact vertebrate tissue. Recent published work defined discrete populations of epithelial stem cells in the adult skin epithelium, which reside in the hair follicle bulge and germ, isthmus, sebaceous gland and inter-follicular epidermis. Adult epidermal and hair follicle stem cells seem to adopt mostly symmetric or unidirectional fate decisions of either one of two possible fates: (1) differentiate and be lost from the tissue or (2) expand symmetrically to self-renew. Asymmetric divisions appear to be mostly implicated in differentiation and stratification of the epidermis. While mechanisms of adult stem cell homeostasis begin to be unraveled, the embryonic origin of the adult epithelial skin stem cells is poorly understood. Recent studies reported Sox9, Lgr6, and Runx1 expression in subpopulations of cells in the embryonic hair placode. These subpopulations seem to act as precursors of different classes of adult epithelial stem cells. In particular, Runx1 regulates a Wnt-mediated cross-talk between the nascent adult-type hair follicle stem cells and their environment, which is essential for timely stem cell emergence, proper maturation, long-term differentiation potential, and maintenance. The new data begin to define the basic dynamics and regulatory pathways governing the ontogeny of adult epithelial stem cells.

Stem Cell Reviews and Reports: The Origin and Fate of Muscle Satellite Cells

Aziz; Sebastian; Dilworth — 2012-01-26

Type: Original Paper

Satellite cells represent the primary population of stem cells resident in skeletal muscle. These adult muscle stem cells facilitate the postnatal growth, remodeling, and regeneration of skeletal muscle. Given the remarkable regenerative potential of satellite cells, there is great promise for treatment of muscle pathologies such as the muscular dystrophies with this cell population. Various protocols have been developed which allow for isolation, enrichment, and expansion of satellite cell derived muscle stem cells. However, isolated satellite cells have yet to translate into effective modalities for therapeutic intervention. Broadening our understanding of satellite cells and their niche requirements should improve our in vivo and ex vivo manipulation of these cells to expedite their use for regeneration of diseased muscle. This review explores the fates of satellite cells as determined by their molecular signatures, ontogeny, and niche dependent programming.

Stem Cell Reviews and Reports: Overcoming Challenges of Ovarian Cancer Stem Cells: Novel Therapeutic Approaches

Aguilar-Gallardo; Rutledge; Martínez-Arroyo; Hidalgo; Domingo; Simón — 2012-01-26

Type: Review Paper

Understanding the genetic and molecular mechanisms of ovarian cancer has been the focus of research efforts working toward the greater goal of improving cancer therapy for patients with residual disease after initial treatment with conventional surgery and neoadjuvant chemotherapy. The focus of this review will be centered on new therapeutic strategies based on Cancer Stem Cells studies of chemoresistant subpopulations, the prevention of metastasis, and individualized therapy in order to find the most successful combination of treatments to effectively treat human ovarian cancer. We reviewed recent literature (1993–2011) of novel treatment approaches to ovarian cancer stem cells. As the focus of ovarian cancer investigation has centered on the cancer stem cell model and the complexities that it presents in the development of effective treatments, the future of treating ovarian cancer lies in utilizing individualized treatment systems that include enhancing existing treatments, aiming for novel therapy targets, managing the plasticity of stem cells to induce cellular differentiation, and regulating oncogenic signaling pathways.

Stem Cell Reviews and Reports: Directed Differentiation of Embryonic Stem Cells Allows Exploration of Novel Transcription Factor Genes for Pancreas Development

Sui; Mehta; Shi; Morahan; Jiang — 2012-01-26

Type: Report

Embryonic stem cells (ESCs) have been promised as a renewable source for regenerative medicine, including providing a replacement therapy in type 1 diabetes. However, they have not yet been differentiated into functional insulin-secreting β cells. This is due partially to the knowledge gap regarding the transcription factors (TFs) required for pancreas development. We hypothesize that, if directed differentiation in vitro recapitulates the developmental process in vivo, ESCs provide a powerful model to discover novel pancreatic TF genes. Guided by knowledge of their normal development and using RT-PCR and immunochemical analyses, we have established protocols for directed differentiation of mouse ESCs into pancreatic progenitors. Microarray analyses of these differentiating ESC cells at days 0, 4, 8 and 15 confirmed their sequential differentiation. By day 15, we found up-regulation of a group of pancreatic progenitor marker genes including Pdx1, Ptf1a, Nkx6.1, Pax4 and Pax6. Consistently, Pdx1-immunoreactive cells were detected on day 15. Most of these Pdx1⁺ cells also expressed Nkx6.1. Bioinformatic analyses of sequential datasets allowed identification of over 20 novel TF genes potentially important for pancreas development. The dynamic expression of representative known and novel genes was confirmed by quantitative real time RT-PCR analysis. This strategy may be modified to study novel regulatory molecules for development of other tissue and organ systems.

Stem Cell Reviews and Reports: An Evolving Model of Hematopoietic Stem Cell Functional Identity

Lensch — 2012-01-26

Type: Original Paper

Easily accessed via venipuncture, blood has been an object of study for centuries. Direct sampling of the hematopoietic tissues in the bone marrow also presents a rather low bar for biopsy acquisition from living donors, especially when compared to other systems in the body such as the heart or brain. This relatively straight-forward ability to obtain cells from the primary anatomical locations of blood cell genesis and differentiation combines with a reliable transplantation assay and well-described surface markers to make the hematopoietic stem cell (HSC) the best understood of all tissue stem cells. HSC biology has been extensively though incompletely investigated over the years. The field continually refreshes itself as new findings require us to reevaluate our understanding of hematopoiesis. After providing a brief overview of the hematopoietic system in general, this review will touch on recent findings in three areas: (1) the niche, (2) HSC migration, and (3) challenges to the “classical” model of hematopoietic ontogeny.

Stem Cell Reviews and Reports: Multipotent Mesenchymal Stromal Cell Therapy and Risk of Malignancies

Casiraghi; Remuzzi; Abbate; Perico — 2012-01-12

Type: Review Paper

Cell therapy with Multipotent Mesenchymal Stromal Cells (MSC) holds enormous promise for the treatment of a large number of degenerative and immune/inflammatory diseases. Their multilineage differentiation potential, immunoprivilege and capacity of promoting recovery of damaged tissues coupled with anti-inflammatory and immunosuppressive properties are the focus of a multitude of clinical studies currently underway. The recognized clinical potential of MSC repairing/immunomodulatory effects now encompasses graft-versus-host disease, hematologic malignancies, cardiovascular diseases, neurologic and inherited diseases, autoimmune diseases, organ transplantation, refractory wounds, and bone/cartilage defects among others. However, it has been suggested that both the need of extensive ex vivo culture for MSC clinical use, and their proangiogenic, anti-apoptotic and immunomodulatory properties may act together as tumor promoters, raising significant safety concerns. This paper will review the available data on in vitro MSC maldifferentiation and the ability of MSC to sustain tumor growth in vivo, with the aim to clarify whether MSC-based therapeutic approaches may carry actual risk of malignancies.

Stem Cell Reviews and Reports: Isolation, Characterization and Differentiation Potential of Cardiac Progenitor Cells in Adult Pigs

2012-01-07

Type: Report
No abstract available.

Alert: Hematopoietic Stem Cell Biology by Kondo, Motonari

2010-05-14

Type: Alert

Alert: Stem Cell Reviews and Reports Impact Factor 3.766

2009-07-20

Type: Alert