Embryology

Zygote: fertilized egg (1 cell), divides through mitosis

Embryogenesis: stages of development between fertilization and birth

Processes of embryogenesis:

·         Fertilization: fusion of the gametes

·         Cleavage: series of mitotic cell divisions after fertilization. The cytoplasm forms many small cells, called blastomeres, which form a sphere (blastula)

·         Gastrulation: Blastomeres change their relative positions; the three germ layers of the embryo form (endoderm, mesoderm, ectoderm)

·         Organogenesis: Cells interact with one another and rearrange themselves to produce tissues and organs

·         Metamorphosis: in some animals, larva become sexually mature adult organisms

·         Gametogenesis: germ cell differentiation occurs

       Epigenesis: the view that organs of an embryo are formed de novo (from scratch) each generation

        Preformation: the view that organs are already present, in miniature form, within an egg and a sperm.

     The Preformation theory is flawed n that it is unable to account for intergenerational genetic variations

Now, most biologists believe that instructions for the formation of the organism are present in a fertilized egg

    Primary germ layers and early organs
        Pander discovered germ layers: ectoderm, mesoderm and endoderm


      Ectoderm: outer layer of embryo, produces epidermis, brain and nervous system
      Mesoderm: generates blood, connective tissue, heart, kidneys, gonads, bones and muscles
     Endoderm: inner layer of embryo, forms epithelium of digestive tube and associated organs

   The four principles of Karl Ernat Von Baer
        1. The general features of a large group of animals appear earlier in development than do the specialized features of a smaller group

     2. Less general characteristics develop from the more general until finally the most specialized appear

       3. An embryo does not pass through the state/formations of other organisms but instead separates itself from them
5    
        4. The embryo of a higher form never resembles an adult of another form, but only an embryo of its own form 



     Blastospore: dimple, marks fixture dorsal (top) side of embryo. Formed at the beginning of gastrulation.

    The blastospore expands to form a ring. Cells that migrate through it become mesoderm
   The endoderm cells are the large yolky cells in the vegetal hemisphere.

   Notochord: rod of mesodermal cells in the most dorsal portion of the embryo. Signals ectodermal cells above it to form a tube and become the nervous system instead of forming the epidermis

    Neural precursor cells elongate, stretch and fold into the embryo, forming the neural tube
    Mesodermal cells near the neural tube and notochord are segmented into somites

    Somites: precursors to the back, skeleton and spine 

      Sources: "Developmental Biology" Tenth Edition - Scott F Gilbert

Stem Cells and Cancer: Cause

It is so far unclear to what extent cancer might be caused by the unchecked replication of mutated stem cells. Cancer stem cells (CSCs) are undifferentiated and replicate indefinitely. some scientists believe these cells arise from mutated stem cells, while others believe them to be the result of mutated progenitors or differentiated cells that have become de-differentiated. Because stem cells can self-renew, their life spans are longer than those of mature differentiated cells. This makes it more likely that CSCs arise from stem cells, as it would take a long time for specialized adult cells to mutate in all the ways necessary for them to obtain the characteristics of cancer cells. Having a long enough lifespan to undergo the mutations needed to form tumors and undergo metastasis would be rare for a differentiated cell. Sox 2, an important factor in maintaining the pluripotent, undifferentiated state of stem cells, has been linked with the proliferation of cancer cells, and some treatments attempt to target sox 2.

Dear stem cell

If you can be anything,
Be my grandfather's brain
Be words he hasn't spoken
In 600 days
And memories of when
He sang in the car with my mother
To show tunes and even now she says
It was her happiest moment
And when it's quiet she whispers
"I wish my dad was really here"

If you can be anything, be
My best friend's lungs
My mother's eyes-
She says they are going
She says she's afraid
She says nothing but I know
She needs you

If you can be anything,
Be
Everything

Stem cells and Musashi

Musashi is a family of RNA- binding proteins that are expressed in the nervous system. Musashi (Msi) proteins are fundamental in progenitor cells. Musashi 1 is a known marker or neural stem cells in humans, and plays an important role in differentiation and in maintaining the stem cell state. Msi1 has also been seen in intestinal epithelial cells, whose stem cells are not well known or understood by scientists. The musashi gene also helps regulate the asymmetric division of sensory organ precursor cells (SOPs). Musashi helps regulate gene expression and translation; it inhibits the translation of the TTK69 protein in certain neural precursor cells. Experiments have shown that the overexpression of Msi1 will lead to proliferation of stem cells, indicating that the protein plays an important role in maintaining and regulating stem cells, as well as serving as a marker by which scientists can identify and isolate neural progenitor cells and stem cells. Msi1 has been observed mainly in the periventricular ependymal cells and astrocytes. These cells are significant in that they maintain a stem cell state while in the adult brain. There is another musashi protein, musashi 2, that appears to have similar functions to those performed by musashi1. Musashi' role in regulating the translation of specific mRNA could be vastly important to our understanding of the nervous system and of stem cells. 


Source: http://www.sciencedirect.com.proxy.library.georgetown.edu/science/article/pii/S001448270500090X

Stem cell niches

Some adult tissues contain stem cells that are continuously regenerating (epidermis, hair follicles, blood cells, sperm cells, etc.), while others do not (nervous system, skeletal muscle). Stem cells produce daughter cells that can be differentiated or remain stem cells. Stem cell niches house continuously proliferating stem cells. They allow for regulated self-renewal of the stem cells and differentiation of those that leave the niche. Bone marrow is a stem cell niche, as are the placenta, the heart, the testes and the umbilical cord. The HSC niche produces many types of blood cells and is located in bone marrow. The HSC niche is able to regulate the production of blood cells, when one is at high altitudes, more red blood cells will be produced, and during an infection more white blood cells will be produced.

Sources: "Developmental Biology" Tenth Edition - Scott F. Gilbert

Stem cell factor (SCF)

SCF supports cell survival, proliferation and differentiation. It acts on many types of cells, including but not limited to stem and progenitor cells.

Stem cell factor is a paracrine factor. It activates MITF (microphthalmia- associated transcription factor), which plays a role in melanocyte and osteoclast development by binding to the receptor tyrosine kinase Kit. The absence of SCF leads to an absence of the Kit protein, which in turn can cause genetic heterogeneity- the creation of similar phenotypes from mutations in various genes (ex. anemia, albinism, sterility). SCF is produced by dermal cells. When Kit binds to SCF, it is able to prevent apoptosis and increase cell division of melanoblast precursors. Without Kit and SCF, neural crest cells would not replicate enough to sufficiently cover the skin. SCF is also needed for the survival and movement of primordial germ cells. It has yet another important function in regulating hematopoietic stem cells (HSCs) in the bone marrow. Without SCF, HSCs, which are undifferentiated and pluripotent stem cells, will die.



Vocabulary:
Melanocyte: specialized skin cell with the melanin pigment

Osteoclast: bone cell with multiple nuclei; helps with the absorption and dissolution of bone

Paracrine: denotes the secretion and binding of a hormone from one organ to another

Transcription factor: a protein that binds to a specific sequence of DNA, regulating the transcription of DNA into mRNA

Apoptosis: programmed cell death

Melanoblast: precursor of a melanocyte, originates in the neural crest

Neural crest: a group of embryonic cells that are not part of the CNS but migrate to and help form many parts of the nervous system

Sources: "Developmental Biology" Tenth edition - Scott F. Gilbert

Stem cell therapy

It has been discovered that the pluripotent stem cells found in embryos can migrate from a fetus to the blood of the pregnant mother. Once there, these stem cells can integrate into the mother's organs and help any diseased or damaged organs. This provides evidence of the potential benefits of embryonic/pluripotent stem cells in medicine. Stem cells could be used to regenerate damaged organs and could even work to combat the effects of aging on the body. Stem cells' undifferentiated and regenerative nature makes them potentially useful in treating diseases including Parkinson's, Alzheimer's, diabetes and cirrhosis, all of which involve the degeneration of adult cells.

While embryonic stem cells are the most useful for treatments, there are issues with using them in medical applications. Since they are not derived from the patient him or herself, they have a distinct genotype and could be rejected by the immune system of the patient. Also, the use of embryonic stem cells presents an ethical dilemma. Scientists have attempted to solve both of these problems with induced pluripotent stem cells, somatic cells that are given pluripotency. It is possible to create these cells because the differentiated state of adult cells must be maintained by transcription factors; in the absence of these factors, a cell will return to an undifferentiated state. IPS cells can be created by adding activated genes including sox 2 and oct4, which inhibit differentiation and support pluripotency. The success of IPS cells was shown in an experiment done on mice in which the IPS cells helped treat sickle-cell anemia.

Sources: "Developmental Biology" Tenth Edition- Scott F Gilbert

Stem cells and sox 2

Sox 2, a member of the Sox B1 family of proteins, plays an important role in stem cells. It helps to regulate the self renewal of embryonic stem cells and to maintain pluripotency and keep stem cells from differentiating. Sox 2 is one of the main transcription factors used to create induced pluripotent cells. Sox 2 has been associated with cancer stem cells and is believed to play a role in initiating skin tumors. It regulates a gene network that is involved in regulating pluripotency and the survival and proliferation of tumor cells. While sox 2 is a necessary transcription factor for maintaining stem cells, and is used by scientists to create induced pluripotent stem cells, it also plays a worrisome role in cancer stem cells. Sox 2 is important in neural stem cells; along with sox 3, it keeps oligodendrocyte precursor cells from becoming mature oligodendrocytes (neural glia that have a myelinating function).

Stem Cells and Cancer: Cure

There are three types of stem cell transplants that are used in cancer treatment: autologous, allogeneic and syngeneic. Autologous transplants entail harvesting stem cells from the cancer patient before they undergo treatment that will destroy the stem cells, freezing these cells and then transplanting them back into the patient after chemo or radiation is complete. This is a useful technique in that it leaves no chance for a negative graft vs host reaction; stem cells derived from another source might be rejected by the patient's body or cause an infection. However, autologous transplants are not always successful. They are most often used to treat leukemias, lymphomas and myeloma. One consequence of autologous transplants is that cancer cells me could potentially be collected along with stem cells when they are harvested from the body; these cancer cells would then be placed back in the patient's body. To combat this, some doctors use purging, a method of treating the harvested stem cells in order to remove any cancer cells. Purging has not proven to be effective thus far, and comes with the downside of potentially damaging or killing stem cells in the process. A more common method for removing the cancer cells from the stem cells is in vivo purging, wherein the patient is given medicine to kill cancer cells after the stem cells have been re-injected into his or her body. Sometimes, two autologous transplants will be done consecutively. This is called a tandem transplant. The tandem treatment is generally reserved for patients with advanced testicular cancer or multiple myeloma, and the risks of a single autologous transplants are compounded by the procedure.

Allogeneic transplants involve transplanting stem cells from an individual with the tissue type of the patient into the patient’s body following chemo or radiation. Occasionally, an allogeneic transplant can be performed by taking blood from the placenta and umbilical cord of a newborn and transplanting it into the cancer patient. This serves as a good source of stem cells, but is still not sufficient to fulfill an adult patient’s stem cell needs. Allogeneic transplants are beneficial in that the transplanted stem cells produce immune cells, which can aid the patient’s immune system in battling the cancerous cells. Also, in contrast with the autologous transplant, the allogeneic transplant does not involve a source that has a finite quantity of stem cells. However, allogeneic transplants are risky in that the transplant (graft) could be rejected by the host. The patient’s immune system might attack the new cells, and might damage or destroy some of its own healthy cells in the process.

The syngeneic transplant is a very specific subset of the allogeneic transplant. It can be done when a cancer patient has an identical sibling. Transplanting stem cells from one identical sibling to another is optimal; there is not a risk of the host rejecting the transplant, nor is there a chance of transplanting cancer cells into the body, which is a risk of the autologous transplant. However, the syngeneic transplant does not have the benefit that other allogeneic transplants have; the graft does not introduce new, foreign immune cells that could help attack cancer cells.

Alzheimer's and Amyloid Beta (powerpoint)

More information on the role of the amyloid beta protein in Alzheimer's. Amyloid beta is only instrumental in creating brain plaques in Alzheimer's patients, and is damaging to neural stem cells which could potentially help treat Alzheimer's.


https://docs.google.com/presentation/d/16UShvcjO5GsGz1D1nr7pagpXJ1ilRjjYTasPiZV7XLw/edit#slide=id.p

Poem

"What do you want to be when you grow up?"

The embryonic stem cell couldn't make his mind up

With pluripotency, he didn't have to decide

He could be anything at all when the time was right

The adult stem cell, who was a bit more mature

Did everything that was expected of her

Followed those in her surrounding space

When a teammate was sick, happily took their place

she was un specialized but her fate was decided

Her heart held the key to her future inside it

Like a caterpillar as a butterfly wakens,

Embryonic and adult had differentiation

Both got their scripts and dressed for their roles

As liver or skin cells, for the good of the whole

With countless costars, they played their parts well

A standing ovation for the stem cell

Stem Cells and Alzheimer's

The prospect of curing Alzheimer's with the use of stem cells is both exciting and daunting. It would be immensely difficult because a large variety of neurons are affected in the brain of an Alzheimer's patient. Therefore, in order to have a positive effect, neural stem cells would have to be able to travel throughout the brain to places that have been damaged and produce many different types of neurons that are able to integrate into the brain and make connections that were once made by the damaged cells. 

So far, tests conducted in mice have had small success, and scientists worry that the brains of Alzheimer's patients would lack the ability to reform important neural connections with the stem cells. Also, stem cells placed in the brain might be damaged by amyloid and tau proteins, proteins that aggregate in the brain due to Alzheimers disease. Stem cells could have potential benefits for Alzheimers patients through their production of neurotrophins. Neurotrophins are proteins that support the development of neurons in a healthy brain, but are scarce in Alzheimer’s patients. Experiments in mice have shown some memory improvement thanks to the neurotrophins produced by neural stem cells.

Scientists have been able to create induced pluripotent stem (iPS) cells that mimic the neurons found in the brains of Alzheimer's patients. The iPS cells release the amyloid beta protein, a main factor in Alzheimer's and a primary component in plaques within the brain. This is highly useful in that it gives scientists the ability to study the disease and how it varies from one individual from the next.

Sources: 

http://www.eurostemcell.org/factsheet/alzheimers-disease-how-could-stem-cells-help

Stem Cells and Multiple Sclerosis

Tests have been performed on mice with MS-like conditions. Stem cells injected into the mice, though fiercely rejected by the immune systems of the subjects, lessened inflammation and repaired some of the myelin sheaths around nerve cells, whose destruction plays a key role in MS. The most positive results came from a study involving the injection of mesenchymal cells (multipotent stromal cells derived from human stem cells). These cells were able to cross the blood- brain barrier and both repair damaged cells and prevent further damage from occurring in the future.



Sources: http://www.usatoday.com/story/news/nation/2014/06/05/stem-cells-multiple-sclerosis/9924469/

Vocabulary

Embryonic stem cell: pluripotent stem cells derived from the inner cell mass of a blastocyst

Adult stem cell: undifferentiated cell, found throughout the body after development, that multiplies by cell division to replenish dying cells and regenerate damaged tissues

Blastocyst: an early-stage preimplantation embryo (3 to 5 days old)

Pluripotency: The ability to differentiate into multiple cell types

Induced pluripotent cell: An adult cell that is genetically reprogrammed to have the pluripotent quality of an embryonic stem cell

Differentiation: The process through which a cell becomes specialized

Progenitor cell: Cell that differentiates into a specialized cell, but is more specific than a stem cell. Unlike a stem cell, it cannot divide indefinitely.

Proliferation: the growth, production and replication of cells

Sources: http://stemcells.nih.gov/Pages/Default.aspx

The Basics

Stem cells are unspecialized cells that can reproduce through mitosis. They are notable in that they are not differentiated: they do not perform a specific function. There are two main types of stem cells- embryonic and adult. Embryonic stem cells have yet to become differentiated into liver cells, brain cells, etc. They are pluripotent; they are able to differentiate into many different types of cells. Adult stem cells differ from embryonic ones in that they are not pluripotent. They differentiate to perform the function that the cells around them perform.  Embryonic stem cells are also able to last longer without differentiating.

Given certain physiologic or experimental conditions, stem cells can be induced to become specialized. Organs such as the gut ad the bone marrow are sites of frequent cell damage and death; stem cells in these regions regularly divide and specialize in order to replace damaged or worn cells. 









Sources: 
http://stemcells.nih.gov/Pages/Default.aspx
http://stemcells.nih.gov/info/basics/pages/basics1.aspx