The adhesion molecule esam1 is a novel hematopoietic stem cell marker

Abstract
Hematopoietic stem cells (HSCs) have been highly enriched using combinations of 12-14 surface markers. Genes specifically expressed by HSCs as compared with other multipotent progenitors may yield new stem cell enrichment markers, as well as elucidate self-renewal and differentiation mechanisms. We previously reported that multiple cell surface molecules are enriched on mouse HSCs compared with more differentiated progeny. Here, we present a definitive expression profile of the cell adhesion molecule endothelial cell-selective adhesion molecule (Esam1) in hematopoietic cells using reverse transcription-quantitative polymerase chain reaction and flow cytometry studies. We found Esam1 to be highly and selectively expressed by HSCs from mouse bone marrow (BM). Esam1 was also a viable positive HSC marker in fetal, young, and aged mice, as well as in mice of several different strains. In addition, we found robust levels of Esam1 transcripts in purified human HSCs. Esam1(-/-) mice do not exhibit severe hematopoietic defects; however, Esam1(-/-) BM has a greater frequency of HSCs and fewer T cells. HSCs from Esam1(-/-) mice give rise to more granulocyte/monocytes in culture and a higher T cell:B cell ratio upon transplantation into congenic mice. These studies identify Esam1 as a novel, widely applicable HSC-selective marker and suggest that Esam1 may play roles in both HSC proliferation and lineage decisions.


Ooi AG, Karsunky H, Majeti R, Butz S, Vestweber D, Ishida T, Quertermous T, Weissman IL, Forsberg EC.

Institute of Stem Cell Biology and Regenerative Medicine, Department of Pathology, Stanford University School of Medicine, California, USA.

Stem cell niche

Stem cell niche is a phrase loosely used in the scientific community to describe the microenvironment in which stem cells are found, which interacts with stem cells to regulate stem cell fate. The word 'niche' can be in reference to the in vivo or in vitro stem cell microenvironment. During embryonic development, various niche factors act on embryonic stem cells to alter gene expression, and induce their proliferation or differentiation for the development of the fetus. Within the human body, stem cell niches maintain adult stem cells in a quiescent state, but after tissue injury, the surrounding micro-environment actively signals to stem cells to either promote self renewal or differentiation to form new tissues. Several factors are important to regulate stem cell characteristics within the niche: cell-cell interactions between stem cells, as well as interactions between stem cells and neighbouring differentiated cells, interactions between stem cells and adhesion molecules, extracellular matrix components, the oxygen tension, growth factors, cytokines, and physiochemical nature of the environment including the pH, ionic strength (e.g. Ca2+ concentration) and metabolites, like ATP, are also important. The stem cells and niche may induce each other during development and reciprocally signal to maintain each other during adulthood.
Scientists are studying the various components of the niche and trying to replicate the in vivo niche conditions in vitro. This is because for regenerative therapies, cell proliferation and differentiation must be controlled in flasks or plates, so that sufficient quantity of the proper cell type are produced prior to being introduced back into the patient for therapy.
Human embryonic stem cells are often grown in fibroblastic growth factor-2 containing, fetal bovine serum supplemented media. They are grown on a feeder layer of cells, which is believed to be supportive in maintaining the pluripotent characteristics of embryonic stem cells. However, even these conditions may not truly mimic in vivo niche conditions.
Adult stem cells remain in an undifferentiated state throughout adult life. However, when they are cultured in vitro, they often undergo an 'aging' process in which their morphology is changed and their proliferative capacity is decreased. It is believed that correct culturing conditions of adult stem cells needs to be improved so that adult stem cells can maintain their stemness over time.
A Nature Insight review defines niche as follows:
"Stem-cell populations are established in 'niches' — specific anatomic locations that regulate how they participate in tissue generation, maintenance and repair. The niche saves stem cells from depletion, while protecting the host from over-exuberant stem-cell proliferation. It constitutes a basic unit of tissue physiology, integrating signals that mediate the balanced response of stem cells to the needs of organisms. Yet the niche may also induce pathologies by imposing aberrant function on stem cells or other targets. The interplay between stem cells and their niche creates the dynamic system necessary for sustaining tissues, and for the ultimate design of stem-cell therapeutics...The simple location of stem cells is not sufficient to define a niche. The niche must have both anatomic and functional dimensions"
—David T. Scadden, The stem-cell niche as an entity of action, Nature, 441 (7097), 1075-1079 (29 June 2006

Essential Stem Cell Methods

ESSENTIAL STEM CELL METHODS




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Edited By
Robert Lanza, Chief Scientific Officer, Advanced Cell Technology, MA, USA; Adjunct Professor, Institute of Regenerative Medicine, Wake Forest University School of Medicine, NC, USA Robert Lanza Advanced Cell Technology 381 Plantation Street Worcester, MA 01605
Irina Klimanskaya, Advance Cell Technology, Worcester, MA, USA

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Contents




Section 1: Organ-Derived Stem Cells

1. Neural Stem Cell Isolation and Characterization ; Rodney L. Rietze and Brent A. Reynolds
2. Neural Stem Cells and Their Manipulation; Evan Snyder
3. Retinal Stem Cells; Thomas A. Reh and Andy J. Fischer
4. Dental Pulp Stem Cells; He Liu, Stan Gronthos and Songtao Shi
5. Spermatogonial Stem Cells; Jon M. Oatley and Ralph L. Brinster
6. Stem Cells in the Lung; Xiaoming Liu, Ryan R. Driskell and John F. Engelhardt
7. Pancreatic Cells and Their Progenitors; Seth J. Salpeter and Yuval Dor
8. Pluripotent Stem Cells from Germ Cells; Candace L. Kerr, Michael J. Shamblott and John D. Gearhart
9. Amniotic Fluid and Placental Stem Cells; Dawn M. Delo, Paolo De Coppi, Georg Bartsch, Jr. and Anthony Atala
10. Cord Blood Stem and Progenitor Cells; Mervin C. Yoder
11. Purification of Hematopoietic Stem Cells Using the Side Population; K.K. Lin and Margaret A. Goodell
12. Microarray Analysis of Stem Cells and Differentiation; Howard Y. Chang
13. Tissue Engineering Using Adult Stem; Cells Daniel Eberli
14. Mesenchymal Stem Cells and Tissue Engineering; Nicholas W. Marion and Jeremy J. Mao


Section II: Embryonic Stem Cells

15. Murine Embryonic Stem Cells; Andras Nagy and Kristina Vintersten
16. Human Embryo Culture; Amparo Mercader, Diana Valbuena and Carlos Sim n
17. Human Embryonic Stem Cells; Douglas Melton
18. Characterization and Evaluation of Human Embryonic Stem Cells; Chunhui Xu
19. Feeder-Free Culture of Human Embryonic Stem Cells; Michal Amit and Joseph Itskovitz-Eldor
20. Neural Stem Cells, Neurons, and Glia; Steven M. Pollard, Alex Benchoua and Sally Lowell
21. Hematopoietic Cells; Malcolm A.S. Moore, Jae-Hung Shieh and Gabsang Lee
22. Cardiomyocytes; Xiangzhong Yang, Xi-Min Guo, Chang-Yong Wang and X. Cindy Tian
23. Insulin-Producing Cells; Insa S. Schroeder, Gabriela Kania, Przemyslaw Blyszczuk
24. Transgene Expression and RNA Interference in Embryonic Stem Cells; Holm Zaehres and George Q. Daley
25. Lentiviral Vector-Mediated Gene Delivery into Human Embryonic Stem Cells; Michal Gropp and Benjamin Reubinoff
26. Engineering Embryonic Stem Cells with Recombinase Systems; Frank Schn tgen, A. Francis Stewart, Harald von Melchner and Konstantinos Anastassiadis
27. Tissue Engineering Using Embryonic Stem Cells; Shahar Cohen, Lucy Leshanski and Joseph Itskovitz-Eldor

Blood Substitutes

“If this really works all the way, then mankind will have taken a big step forward. This is like landing on the moon."

-Dr. Pierre LaFolie

Types of stem cells

ASC (adipose stem cells)
CSC (cochlear stem cells)
CTP (connective tissue progenitors)
ESC (embryonic stem cells)
HSC (hematopoietic stem cells)
HB1 (AC133+ hemangioblasts from umbilical cord blood)
iPS (induced pluripotent stem cells)
MSC (mesenchymal stem cells)
MAPC (multi-potent adult stem cells)
NSC (neural stem cells/oligodendrocyte progenitors)
SKMB (skeletal myoblasts and muscle stem cells), and
UCB (umbilical cord blood derived stem cells)

Professor Martin L Olsson

The Regional Blood Center, Lund University Hospital, Sweden
Martin Olsson is a Professor of Transfusion Medicine at Lund University, Lund, Sweden and a Visiting Associate Professor/Lecturer at Harvard Medical School, Boston, MA, USA. He received his medical degree and PhD at Lund University. His main clinical and research interests are in the molecular genetics of red cell surface markers with a special emphasis on carbohydrate histo-blood group systems and blood typing. His scientific contributions have focused on clarifying the correlation between red cell phenotypes and the underlying genetic polymorphisms, as well as glycosyltransferase function in different blood groups. He is also interested in pathogen-related aspects of blood group antigens and different mechanisms of protection against hemolysis, including exoglycosidase-treated red cells for ABO-universal transfusion. Dr. Olsson serves as Associate Editor of Transfusion Medicine and is a member of the Editorial Board of Transfusion. His awards include the Jean Julliard Prize from the International Society of Blood Transfusion, the Race and Sanger Award from the British Blood Transfusion Society, the Fernstrِm Prize at Lund University and the Hain Foundation Prize

scapegoating

scapegoat

In the Old Testament, a goat that was symbolically burdened with the sins of the people and then killed on Yom Kippur to rid Jerusalem of its iniquities. Similar rituals were held elsewhere in the ancient world to transfer guilt or blame. In ancient Greece, human scapegoats were beaten and driven out of cities to mitigate calamities. In early Roman law, an innocent person was allowed to assume the penalty of another; Christianity reflects this notion in its belief that Jesus died to atone for the sins of mankind.

Artificial Blood Products And Artificial Oversight?

Artificial blood products increased the risk of death by 30 percent and almost tripled the risk of heart attacks in 16 clinical trials, according to a study in the Journal of the American Medical Association. The researchers write that the FDA should have stopped the studies eight years ago, but meanwhile five trials are still under way and another is about to begin.

Eight years ago, the FDA received data on individual studies showing increased risks that should have triggered suspension of testing until a large-scale analysis could be conducted, according to the researchers, who say the FDA should end the trials and Congress should review rules forcing the agency to keep info on new products confidential for competitive reasons.

“One straightforward solution to these problems would be for Congress to reverse the FDA’s policy of treating as confidential all corporate materials submitted during the product development process, including the investigational drug application,” the researchers wrote. The blood products studied were made by Baxter International, Biopure, Hemosol BioPharma, Northfield Laboratories and Sangart.

“If you have secret science, things like this can happen,” Charles Natanson, a septic shock researcher at the National Institutes of Health, tells Bloomberg News. “Once you’ve randomized patients, your results can’t be a trade secret. It’s a measure of protection to the American public.”


But Jay Epstein, director of the FDA’s office of blood research and review, tells Bloomberg that analyzing several studies together as one has its limitations. And he adds that the agency also has unpublished info not available to the study’s authors that shows potential benefits of artificial blood. It’s not clear whether that info will be discussed at an FDA workshop being held tomorrow to review the products.

Filgrastim

Filgrastim is a granulocyte colony-stimulating factor (G-CSF) analog used to stimulate the proliferation and differentiation of granulocytes. It is produced by recombinant DNA technology. The gene for human granulocyte colony-stimulating factor is inserted into the genetic material of Escherichia coli. The G-CSF then produced by E. coli is only slightly different from G-CSF naturally made in humans. It is marketed by Amgen with the brand name Neupogen, Reliance Biopharmaceuticals with the brand name Religrast,Zenotech Laboratories Limited with the brand name Nugrafand also by Raichem lifesciences with the brand name Shilgrast.Filgrastim is used to treat neutropenia (a low number of neutrophils), stimulating the bone marrow to increase production of neutrophils. Causes of neutropenia include chemotherapy and bone marrow transplantation.Filgrastim is also used to increase the number of hematopoietic stem cells in the blood before collection by leukapheresis for use in hematopoietic stem cell transplantation.It is produced by many companies worldwide.

Lund Stem Cell Center

Established in January 2003, the center focuses on stem cell and developmental biology of the central nervous and blood systems, and development of stem cell and cell replacement therapies in these organ systems as well as research in non-mammalian model systems.

Consisting of many strong research groups and almost 130 people under "one roof", the Center is already one of the largest in the field, with the goal of becoming a major force in translational research and career development in biomedical research.

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