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Stem cells — hype and hope Nature   406 , 361 - 364 (2000)
[object Object],Stem cells have become the centre of so much attention because they turn into all the different cell types that make up complex organisms, and they promise to perform this remarkable feat on demand. The implications for medicine are profound, but practical and ethical barriers stand  in the way .
The Embryonic Stem Cell ,[object Object],[object Object],[object Object]
 
 
[object Object],Are Embryonic Stem Cells truly Pluripotent?
Reported differentiated cell types from mouse ES cells  in vitro
Controlling cell fate ,[object Object]
[object Object],[object Object],[object Object],[object Object],The behavior of stem cells depends on their history and on their local context or niche.
Germ cells and cancer ,[object Object],[object Object]
[object Object],[object Object],[object Object],[object Object]
Embryonic stem cells ,[object Object],[object Object]
[object Object],[object Object],[object Object]
[object Object],[object Object],[object Object],[object Object],[object Object],what is the motivation for working with early human cells?
Adult stem cells ,[object Object],[object Object],Stem cells are abundant in the developing brain and in two areas of the adult central nervous system (CNS): the hippocampus and the olfactory bulb. Cells in the brain are not replaced as efficiently as blood cells, however, so we cannot define adult CNS stem cells in the same way as haematopoietic stem cells. But CNS stem cells can be easily grown in the lab and — under the right conditions — differentiate efficiently in culture dishes into neurons, oligodendrocytes (the cells that insulate the electrical signals passing down axons in the nervous system) and astrocytes (another type of non-neuronal cell in the CNS). The many cell types of the peripheral nervous system are also generated from a stem cell.
Figure 1  Stem-cell transitions. At least in the lab, stem cells are not always restricted to one particular pathway of differentiation. For example, central nervous system (CNS) stem cells form the different cell types of the CNS, but can also differentiate into haematopoietic (blood) stem cells. Blood stem cells in turn form the different cell types found in blood, as shown here, but can also differentiate into skeletal muscle stem cells (which differentiate into skeletal muscle cells, pictured) and central nervous system cells. Embryonic stem (ES) cells are pluripotent, and contribute to all of the tissues of developing mammals. For simplicity, only a few of the stem-cell types that ES cells can produce are shown here.
[object Object],[object Object],[object Object],[object Object],[object Object]
Clinical potential and pitfalls ,[object Object],[object Object],[object Object],[object Object],[object Object],[object Object]
[object Object],[object Object],[object Object],[object Object],[object Object]
[object Object]
[object Object],[object Object],[object Object],[object Object],'Immortalized' cells grow indefinitely in culture, without forming tumors when injected into animals.
Figure 3  In principle, liver diseases might be treatable by transplanting isolated liver cells (hepatocytes). Donor livers, however, provide only a fraction of the cells needed for clinical transplantation, and primary liver cells do not proliferate significantly in tissue culture. When hepatocyte stem cells have been immortalized by introducing growth-promoting genes into them, they proliferate in culture, retain their ability to differentiate into hepatocytes, and function in animal models of liver failure16. This photomicrograph of a spleen section shows a transplanted cell (arrow) with hepatocellular morphology three months after transplantation. Scale bar,  10  m.
[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object]
The image shows the chromosomes of a female bone marrow donor in pink. The recipient's cells are in pink. The resut is a fused cell that contains chomosomes from the donor and the recipient.   Photo: Wang, et al,  Nature , March 30, 2003.
Damaged liver cells are in brown. Blue indicated the repopulation of new, healthy cells.    Photo: Wang, et al,  Nature , March 30, 2003.   The different colors indicate the genetic expression of various cells, proving that cells have fused and still carry characteristics of both the bone marrow donor and the recipient.   Photo: Vassilopoulos, et al,  Nature , March 20, 2003.
 
 
 
 
 
 
In recent years stem cells are subject of increasing scientific interest because of their potential utility in numerous biomedical applications.  Stem cell technology provides unprecedented opportunities not only for investigating new ways to prevent and treat a vast arrays of diseases but also for changing the way we identify new molecular targets, discover and develop new drugs, as well as test them for safety.  Because stem cells are a self-renewing population of cells, they can be continuously cultured in an undifferentiated state and give rise to more specialized cells of the human body, such as heart, liver, bone marrow, blood vessels, pancreatic islets and nerve cells. Therefore, stem cells offer an important new tool to develop unique in vitro model systems for testing drugs and chemicals and potentially predict or anticipate toxicity in humans.  The following review provides an overview on the evolving concept of applying stem cell technology to biomedical research and also describes potential applications of stem cells in the area of toxicology. Emphasis has been placed in the use of 1) bone marrow-derived adult stem cells as an alternative source of critical cells required to perform needed safety evaluation in human cells, 2) hepatocyte-like cells from human placenta for drug metabolism and toxicity studies 4) embryonic stem cells for target validation and in vitro toxicology and 5) adult stem cells to screen genotoxic/epigenetic toxins and toxicants and their potential to help develop a biological-based risk assessment of toxic chemical exposure to human beings.
Studies of stem cells will help in understanding the development and function of organs in mammals.  ,[object Object]
What are embryonic stem cells? ,[object Object]
Where do embryonic stem cells come from? ,[object Object]
Why are embryonic stem cells important? ,[object Object],[object Object],[object Object],[object Object],Continued….
[object Object],[object Object],[object Object],[object Object],Why are embryonic stem cells important?
How might embryonic stem cells be used to treat disease? ,[object Object],[object Object],[object Object]
What are the benefits of studying embryonic stem cells? ,[object Object],[object Object],[object Object],[object Object]
Why not derive stem cells from adults? ,[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object]
 
Extrapolation to humans
In the last few years, the great progress of certain fields, such as molecular biology and development, has allowed a detailed knowledge of mechanisms implicated in cellular programming.  This has permitted a rapid and unexpected advance in therapeutic cellular strategies. Thus, it has been possible to discover mechanisms involved in cellular differentiation and therefore has opened possibilities for human cellular manipulation and function replacement of damaged cells.  Embryonic stem cells, have been obtained from the embryoblast. A lot of types of cellular lineages that include neurons, glial cells, pancreatic islets cells, hepatic cells, osteoblast and adipocytes, have been derived from mouse embryonic stem cells. In the same way, cellular lineages have been obtained by nuclear transference techniques capable of generating embryonic clones. Some scientist intend to evade by this approach, the bioethic reproval for human cloning, emphasizing that this is a "therapeutic cloning".
The Dilemma of Embryonic Stem Cell Research ,[object Object],[object Object],[object Object],[object Object]

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Stem Cell

  • 1. Stem cells — hype and hope Nature 406 , 361 - 364 (2000)
  • 2.
  • 3.
  • 4.  
  • 5.  
  • 6.
  • 7. Reported differentiated cell types from mouse ES cells in vitro
  • 8.
  • 9.
  • 10.
  • 11.
  • 12.
  • 13.
  • 14.
  • 15.
  • 16. Figure 1 Stem-cell transitions. At least in the lab, stem cells are not always restricted to one particular pathway of differentiation. For example, central nervous system (CNS) stem cells form the different cell types of the CNS, but can also differentiate into haematopoietic (blood) stem cells. Blood stem cells in turn form the different cell types found in blood, as shown here, but can also differentiate into skeletal muscle stem cells (which differentiate into skeletal muscle cells, pictured) and central nervous system cells. Embryonic stem (ES) cells are pluripotent, and contribute to all of the tissues of developing mammals. For simplicity, only a few of the stem-cell types that ES cells can produce are shown here.
  • 17.
  • 18.
  • 19.
  • 20.
  • 21.
  • 22. Figure 3 In principle, liver diseases might be treatable by transplanting isolated liver cells (hepatocytes). Donor livers, however, provide only a fraction of the cells needed for clinical transplantation, and primary liver cells do not proliferate significantly in tissue culture. When hepatocyte stem cells have been immortalized by introducing growth-promoting genes into them, they proliferate in culture, retain their ability to differentiate into hepatocytes, and function in animal models of liver failure16. This photomicrograph of a spleen section shows a transplanted cell (arrow) with hepatocellular morphology three months after transplantation. Scale bar, 10 m.
  • 23.
  • 24. The image shows the chromosomes of a female bone marrow donor in pink. The recipient's cells are in pink. The resut is a fused cell that contains chomosomes from the donor and the recipient. Photo: Wang, et al, Nature , March 30, 2003.
  • 25. Damaged liver cells are in brown. Blue indicated the repopulation of new, healthy cells. Photo: Wang, et al, Nature , March 30, 2003. The different colors indicate the genetic expression of various cells, proving that cells have fused and still carry characteristics of both the bone marrow donor and the recipient. Photo: Vassilopoulos, et al, Nature , March 20, 2003.
  • 26.  
  • 27.  
  • 28.  
  • 29.  
  • 30.  
  • 31.  
  • 32. In recent years stem cells are subject of increasing scientific interest because of their potential utility in numerous biomedical applications. Stem cell technology provides unprecedented opportunities not only for investigating new ways to prevent and treat a vast arrays of diseases but also for changing the way we identify new molecular targets, discover and develop new drugs, as well as test them for safety. Because stem cells are a self-renewing population of cells, they can be continuously cultured in an undifferentiated state and give rise to more specialized cells of the human body, such as heart, liver, bone marrow, blood vessels, pancreatic islets and nerve cells. Therefore, stem cells offer an important new tool to develop unique in vitro model systems for testing drugs and chemicals and potentially predict or anticipate toxicity in humans. The following review provides an overview on the evolving concept of applying stem cell technology to biomedical research and also describes potential applications of stem cells in the area of toxicology. Emphasis has been placed in the use of 1) bone marrow-derived adult stem cells as an alternative source of critical cells required to perform needed safety evaluation in human cells, 2) hepatocyte-like cells from human placenta for drug metabolism and toxicity studies 4) embryonic stem cells for target validation and in vitro toxicology and 5) adult stem cells to screen genotoxic/epigenetic toxins and toxicants and their potential to help develop a biological-based risk assessment of toxic chemical exposure to human beings.
  • 33.
  • 34.
  • 35.
  • 36.
  • 37.
  • 38.
  • 39.
  • 40.
  • 41.  
  • 43. In the last few years, the great progress of certain fields, such as molecular biology and development, has allowed a detailed knowledge of mechanisms implicated in cellular programming. This has permitted a rapid and unexpected advance in therapeutic cellular strategies. Thus, it has been possible to discover mechanisms involved in cellular differentiation and therefore has opened possibilities for human cellular manipulation and function replacement of damaged cells. Embryonic stem cells, have been obtained from the embryoblast. A lot of types of cellular lineages that include neurons, glial cells, pancreatic islets cells, hepatic cells, osteoblast and adipocytes, have been derived from mouse embryonic stem cells. In the same way, cellular lineages have been obtained by nuclear transference techniques capable of generating embryonic clones. Some scientist intend to evade by this approach, the bioethic reproval for human cloning, emphasizing that this is a "therapeutic cloning".
  • 44.