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Mulitcellular Organisms

Stem Cells (2022 Update)

Stem cells are primitive cells that give rise to other types of cells. Also called progenitor cells, there are several kinds of stem cells. Totipotent cells are considered the "master" cells of the body because they contain all the genetic information needed to create all the cells of the body plus the placenta, which nourishes the human embryo. Human cells have this capacity only during the first few divisions of a fertilized egg. In the Bush era research on human embryonic stem cell lines may be conducted with Federal support if the cell lines meet the President’s criteria under the executive order announced on August 9, 2001.
Differentiation Stem Cell There are 69 cell lines registered with NIH - National Institutes of Health, 15 of these are available for shipment. President Obama signed an executive order on March 9, 2009 to lift the ban under the Stem Cell Policy in the Bush era. He also directed the NIH to develop revised guidelines to ensure that such research "never opens the door to the use of cloning for human reproduction". Legally it is possible that Obama's successor can in turn reverse the Obama executive order. Now back to the stem cell:

Figure 10-13a Differentiation Pathway

Figure 10-13b Stem Cell Cycle
[view large image]

After 3 - 4 divisions of totipotent cells, there follows a series of stages in which the cells become increasingly specialized. The next stage of division results in pluripotent cells, which are highly versatile and can give rise to any cell type except the cells of the placenta. At the next stage, cells become multipotent, meaning they can give rise to several other cell types, but those types are limited in number. An example of multipotent cells is hematopoietic cells - blood stem cells that can develop into several types of blood cells, but cannot develop into brain cells. At the end of the long chain of cell divisions that make up the embryo are "terminally differentiated" cells - cells that are permanently committed to a specific function. Figure 10-13a shows the pathway from embryonic stem cell to multipotent stem cell and on to the different type of specialized cells.

Multipotent stem cell is self-renewing. When the stem cell divides, one of the two daughter cells may go on to give rise
to other types of cell, whereas the other daughter cell remains a stem cell, capable of dividing again and always giving one daughter to diversification. (See Figure 10-14b)

Blood cells in human body are replaced every 120 days. The replacement comes from the multipotent stem cell in the bone marrow. Skin cells are shed every few weeks. The replacement comes from the multipotent stem cell at the base of the skin (the basal layer). Scientists are still looking for the the neural stem cell. Its identity, location and potential remain unclear.

It has been long held that differentiated cells cannot be altered or caused to behave in any way other than the way in which they have been naturally committed. New research, however, has called that assumption into question. In recent stem cell experiments, scientists have been able to persuade blood cells to behave like neurons, or brain cells.

Recent research in 2004 has located the neural stem cells in the subventricular zone (SVZ). It is a principal source of adult neural stem cells in the rodent brain, generating thousands of olfactory bulb neurons every day. These neurons migrate from the SVZ to the brain region concerned with sensing smell. But such stem cells have become non-functional in adult human. The systematic decrease in the extent of adult neurogenesis during vertebrate evolution may be the result of an adaptation to keep neuronal populations with their accumulated experience for an entire lifespan. Therefore, the therapeutic transplantation of new neurons to regions of the human brain that are responsible for more advanced brain functions may be counterproductive, but their transplantation to other regions, such as the sensory or motor systems of the brain, could have enormous clinical significance. The identification of the cellular and molecular mechanisms that prevent adult neural stem cells from becoming integrated into functional neuronal networks would be a major accomplishment for repairing brain damage or lost neurons.

The Nature magazine has kindly made available a poster (2.8 MB in pdf format), which provides an overview of distinct embryonic and adult stem-cell types.

A 2012 paper in Nature reported that Optic Cup (a rounded goblet of retinal tissue in the back of the eye) has been grown from
Stem Cells to Optic Cup stem cell culture (from mouse for now). The process involves carefully controlled external environment (such as number of stem cells ~ 9000 in this case, the concentration of growth factors, and the addition of cell-culture ingredient called Matrigel etc). After introducing a right mixture into the stem cells, the rest is up to themselves to run their internal programs without any other supporting tissue. The optic cup emerge naturally in about 24 days (see Figure 10-13c). This feat has obvious implication for repairing vision.

Figure 10-13c From Stem Cells to Optic Cup [view large image]

Further researches are expending into the areas of pituitary gland, cerebral cortex, a complete photoreceptors, and cerebellum, but not the whole brain - that would be enormously difficult and ethically fraught.

[2022 Update]

Stem Cell Activation Cues Stem cells are similar to common cells. It contains a nucleus, mitochondria, endoplasmic reticulum, ribosomes, membrane ... (Figure 10-13d) - nothing out of the ordinary. What makes them standing out is their ability of differentiating into specialized cell type by cue (Figure 10-13e). As explained further in the followings, there are different types of stem cells according to their potency (ability) and different kinds of activation cues for activating different genes (to produce specialized cell type).

Figure 10-13d Stem Cell

Figure 10-13e Activation Cues [view large image]

    Stem Cell Types :
  1. Totipotent Cell - Totipotent stem cells are unique as they have the greatest developmental potential compared with other stem cells. Examples include :
  2. Pluripotent Stem Cells (PSC) - this is the embryonic stem cell which has all the properties of the totipotent cell except the ability of generating placenta. These cells have the ability to undergo self-renewal and to give rise to all cells of the tissues of the body as shown in Figure 10-13f. The discovery in 2006 that human and mouse fibroblasts could be reprogrammed to generate induced pluripotent stem cells (iPSCs) with qualities remarkably similar to embryonic stem cells has created a valuable new source of pluripotent cells for drug discovery, cell therapy, and basic research. See "Induced Pluripotent Stem Cells: Problems and Advantages when Applying them in Regenerative Medicine" for a thorough review of iPSC.

  3. Multipotent Stem Cells - They have the ability to develop specific types of cells (terminally differentiated cells). Ordering according to the lineage (from endoderm, to mesoderm, and ectoderm) as shown in Figure 10-13f, examples include :
    There are three different types of differentiated cells:
  1. Those which are terminally differentiated and do not have any precursor left for their repair of any injury which may happen in the future, such as heart cells.
  2. The second type of differentiated cells are those which are kept in the G0 phase and as and when they are required they are used for replenishing the dead cells such as skin fibroblasts, smooth muscle cells, the endothelial cells that line blood vessels, and the epithelial cells of most internal organs, such as the liver, pancreas, kidney, lung, prostate, and breast. Such process is called mitosis.
  3. The third type of cells are those differentiated cells which include blood cells, epithelial cells of the skin, and the epithelial cells lining the digestive tract which have short life spans and must be replaced by continual cell proliferation in adult animals. They are replaced via the proliferation of multipotent stem cells.

  4. See a "List of human cell types derived from the germ layers".

Xenobot - By 2020, the African Frog, Xenopus has become valuable model organism to study early embryonic development as well as
Xenobot, Generation Xenobot, Replcation for research into human genetic disease (complementary to the more commonly used mouse and zebrafish). Recently, it is found that the stem cells extracted from the early embryo can replicate itself (touted as a new way of reproduction - the so-called "kinetic replication" ???). Closer examination reveals that it can be explained by the various cues (as presented above) on the stem cells.

Figure 10-13g2 Xenobot,
Stem Cells Extraction

Figure 10-13g3 Xenobot,

[End of 2022 Update]

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