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Adult Stem Cells, Homeostasis,
and Regenerative Medicine
What are Adult Stem Cells?
• An adult stem cell is an undifferentiated (or
partially-differentiated) cell found in tissues
and organs
• They can self-renew and differentiate to
become most or all of the specialized cell
types within their specific tissue lineage.
• Adult stem cells
– Maintain cell populations
– Help you heal
– Play a role in aging
Homeostasis
• The ability to regulate internal conditions,
usually by a system of feedback controls
Stabilize health and functioning, regardless of the
outside changing conditions.
• One piece of homeostasis is the constant or
periodic generation of new cells to replace
old, damaged, and dying cells
• Adult stem cells fulfill this role through the
process of regeneration
How Regeneration Works
• Adult stem cells normally remain quiescent (non-
dividing) for relatively long periods of time until they
are activated by signals to maintain tissues
• When activated they divide through a process called
asymmetric cell division
• Through this process they are able to maintain their
populations and differentiate into the desired cell
types by the creation of a progenitor cell
• A progenitor cell, in contrast to stem cells, is already
far more specific: they are pushed to differentiate into
their "target" cell.
Asymmetric Cell Division
1. Proliferates
2. Maintains pop.
3. Creates Progenitor Cell
Progenitor cell
Stem cell Stem cell
Location of Adult Stem Cells
• Adult stem cells and progenitor cells reside
through out your body
• These stem cells reside in a specific area of
each tissue called the “stem cell niche”
• This niche is a particular microenvironment
that fosters the growth of resident stem cells
• Mutations in cells, signals they receive, and
changes in the microenvironment can activate
a stem cell
Types of Adult Stem Cells
Hematopoietic stem cells: blood and immune system
Mesenchymal stem cells: bone, cartilage, fat, muscle,
tendon/ligament
Neural stem cells: neurons, glial cells
Epithelial stem cells: skin, linings
Hematopoietic stem cells
Give rise to all the blood cell types:
• Myeloid (monocytes and macrophages,
neutrophils, basophils, eosinophils, erythrocytes,
megakaryocytes/platelets, dendritic cells)
• Lymphoid (T-cells, B-cells, NK-cells)
Found in the bone marrow from very early on in
development, as well as in umbilical cord
blood and placental tissue
Mesenchymal stem cells
• These stem cells will
differentiate into:
– cartilage cells (chondrocytes)
– muscle cells (myocytes)
– fat cells (adipocytes)
– tendons, ligaments, and
connective tissue (epithelial
cells including osteoblasts)
• These cells are located
throughout the body
• Bone marrow, fat, and cord
blood are easiest to isolate
Smooth muscle cells (red)
© CIRM
Neural stem cells
• They are located in:
• Subventricular zone lining the
lateral ventricles, where they
give rise to newly-born
neurons that migrate to the
olfactory bulb via the rostral
migratory stream
• Subgranular zone, part of the
dentate gyrus of the
hippocampus
• Neural stem cells (also
called Neural precursor
cells) give rise to neurons,
oligodendrocytes, and
astrocytes
Top: Section of the
hippocampus, blue
dots are neural stem
cells
Left: Mature neuron
(red)
© CIRM
Epithelial stem cells
• Give rise to epithelial cells
which constitute 60 percent
of the differentiated cells in
the body.
• Responsible for covering
the internal (i.e. intestinal
lining) and external surfaces
(i.e. skin) of the body,
including the lining of
vessels, glands, and other
cavities.
• Epithelial stem cells are also
found in the bulge region of
the hair follicle
Retinal pigment epithelial cells
© CIRM
Adult Stem Cell Therapies
Bone Marrow Transplant
Tissue Specific Organs
• In November 2008, scientists
in Spain carried out a trachea
transplant for a woman whose
windpipe had been damaged
by tuberculosis.
• The doctors took adult stem
cells and some other cells
from the healthy right airway
of the woman needing the
trachea transplant, grafted
those cells onto the stripped-
down donated (cadaver)
trachea, and marinated the
trachea in chemicals in a lab to
coax the trachea into
rebuilding itself.
Clinical Trials
Clinical trials are conducted in phases. The trials at each phase have a
different purpose and help scientists answer different questions:
Phase I trials: researchers test an experimental drug or treatment in a
small group of people (20-80) for the first time to evaluate its safety,
determine a safe dosage range, and identify side effects.
Phase II trials: the experimental study drug or treatment is given to a
larger group of people (100-300) to see if it is effective and to further
evaluate its safety.
Phase III trials: the experimental study drug or treatment is given to large
groups of people (1,000-3,000) to confirm its effectiveness, monitor side
effects, compare it to commonly used treatments, and collect information
that will allow the experimental drug or treatment to be used safely.
Phase IV trials: post marketing studies delineate additional information
including the drug's risks, benefits, and optimal use.
Risk vs. Benefits of Participating in a
Clinical Trial
Risk
• The patient must stop taking
other treatments before the trial
• There may be unpleasant, serious
or even life-threatening side
effects to experimental
treatment.
• The experimental treatment may
not be effective for the
participant, or given a placebo
• The protocol may require more of
their time and attention than
would a non-protocol treatment,
including trips to the study site,
more treatments, hospital stays
or complex dosage requirements.
Benefit
• Play an active role in their own
health care.
• Gain access to new research
treatments before they are
widely available.
• Obtain expert medical care at
leading health care facilities
during the trial.
• Help others by contributing to
medical research.
• The patient may get better as a
result of the experimental
treatment.
• Patients who receive the placebo
are usually, but not always, given
access to the treatment once the
trial ends
Stem Cell Tourism
• In what is called “stem cell tourism” patients travel to
other countries with less restrictions to receive stem
cell therapies.
• Sometimes experimental and can be dangerous
• There are many legitimate therapies going through
national regulatory processes in these countries.
• December 2008 study of stem cell clinic web sites
• Sites claimed to treat a range of diseases that go beyond
the scope of the early evidence on stem cells' efficacy
• Played up the benefits and talked little about risks
• Each treatment costs around $21,500

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Epithelia stem cells

  • 1. Adult Stem Cells, Homeostasis, and Regenerative Medicine
  • 2. What are Adult Stem Cells? • An adult stem cell is an undifferentiated (or partially-differentiated) cell found in tissues and organs • They can self-renew and differentiate to become most or all of the specialized cell types within their specific tissue lineage. • Adult stem cells – Maintain cell populations – Help you heal – Play a role in aging
  • 3. Homeostasis • The ability to regulate internal conditions, usually by a system of feedback controls Stabilize health and functioning, regardless of the outside changing conditions. • One piece of homeostasis is the constant or periodic generation of new cells to replace old, damaged, and dying cells • Adult stem cells fulfill this role through the process of regeneration
  • 4. How Regeneration Works • Adult stem cells normally remain quiescent (non- dividing) for relatively long periods of time until they are activated by signals to maintain tissues • When activated they divide through a process called asymmetric cell division • Through this process they are able to maintain their populations and differentiate into the desired cell types by the creation of a progenitor cell • A progenitor cell, in contrast to stem cells, is already far more specific: they are pushed to differentiate into their "target" cell.
  • 5. Asymmetric Cell Division 1. Proliferates 2. Maintains pop. 3. Creates Progenitor Cell Progenitor cell Stem cell Stem cell
  • 6.
  • 7. Location of Adult Stem Cells • Adult stem cells and progenitor cells reside through out your body • These stem cells reside in a specific area of each tissue called the “stem cell niche” • This niche is a particular microenvironment that fosters the growth of resident stem cells • Mutations in cells, signals they receive, and changes in the microenvironment can activate a stem cell
  • 8. Types of Adult Stem Cells Hematopoietic stem cells: blood and immune system Mesenchymal stem cells: bone, cartilage, fat, muscle, tendon/ligament Neural stem cells: neurons, glial cells Epithelial stem cells: skin, linings
  • 9. Hematopoietic stem cells Give rise to all the blood cell types: • Myeloid (monocytes and macrophages, neutrophils, basophils, eosinophils, erythrocytes, megakaryocytes/platelets, dendritic cells) • Lymphoid (T-cells, B-cells, NK-cells) Found in the bone marrow from very early on in development, as well as in umbilical cord blood and placental tissue
  • 10. Mesenchymal stem cells • These stem cells will differentiate into: – cartilage cells (chondrocytes) – muscle cells (myocytes) – fat cells (adipocytes) – tendons, ligaments, and connective tissue (epithelial cells including osteoblasts) • These cells are located throughout the body • Bone marrow, fat, and cord blood are easiest to isolate Smooth muscle cells (red) © CIRM
  • 11. Neural stem cells • They are located in: • Subventricular zone lining the lateral ventricles, where they give rise to newly-born neurons that migrate to the olfactory bulb via the rostral migratory stream • Subgranular zone, part of the dentate gyrus of the hippocampus • Neural stem cells (also called Neural precursor cells) give rise to neurons, oligodendrocytes, and astrocytes Top: Section of the hippocampus, blue dots are neural stem cells Left: Mature neuron (red) © CIRM
  • 12. Epithelial stem cells • Give rise to epithelial cells which constitute 60 percent of the differentiated cells in the body. • Responsible for covering the internal (i.e. intestinal lining) and external surfaces (i.e. skin) of the body, including the lining of vessels, glands, and other cavities. • Epithelial stem cells are also found in the bulge region of the hair follicle Retinal pigment epithelial cells © CIRM
  • 13. Adult Stem Cell Therapies Bone Marrow Transplant
  • 14. Tissue Specific Organs • In November 2008, scientists in Spain carried out a trachea transplant for a woman whose windpipe had been damaged by tuberculosis. • The doctors took adult stem cells and some other cells from the healthy right airway of the woman needing the trachea transplant, grafted those cells onto the stripped- down donated (cadaver) trachea, and marinated the trachea in chemicals in a lab to coax the trachea into rebuilding itself.
  • 15. Clinical Trials Clinical trials are conducted in phases. The trials at each phase have a different purpose and help scientists answer different questions: Phase I trials: researchers test an experimental drug or treatment in a small group of people (20-80) for the first time to evaluate its safety, determine a safe dosage range, and identify side effects. Phase II trials: the experimental study drug or treatment is given to a larger group of people (100-300) to see if it is effective and to further evaluate its safety. Phase III trials: the experimental study drug or treatment is given to large groups of people (1,000-3,000) to confirm its effectiveness, monitor side effects, compare it to commonly used treatments, and collect information that will allow the experimental drug or treatment to be used safely. Phase IV trials: post marketing studies delineate additional information including the drug's risks, benefits, and optimal use.
  • 16. Risk vs. Benefits of Participating in a Clinical Trial Risk • The patient must stop taking other treatments before the trial • There may be unpleasant, serious or even life-threatening side effects to experimental treatment. • The experimental treatment may not be effective for the participant, or given a placebo • The protocol may require more of their time and attention than would a non-protocol treatment, including trips to the study site, more treatments, hospital stays or complex dosage requirements. Benefit • Play an active role in their own health care. • Gain access to new research treatments before they are widely available. • Obtain expert medical care at leading health care facilities during the trial. • Help others by contributing to medical research. • The patient may get better as a result of the experimental treatment. • Patients who receive the placebo are usually, but not always, given access to the treatment once the trial ends
  • 17. Stem Cell Tourism • In what is called “stem cell tourism” patients travel to other countries with less restrictions to receive stem cell therapies. • Sometimes experimental and can be dangerous • There are many legitimate therapies going through national regulatory processes in these countries. • December 2008 study of stem cell clinic web sites • Sites claimed to treat a range of diseases that go beyond the scope of the early evidence on stem cells' efficacy • Played up the benefits and talked little about risks • Each treatment costs around $21,500

Editor's Notes

  1. Undifferentiated - Of, or describing a cell that has not yet acquired a special structure and function; pertaining to an immature cell or a primitive cell Self-renew - the ability to go through numerous cycles of cell division while maintaining the undifferentiated state. Differentiate - the process by which a less specialized cell becomes a more specialized cell type Specialized - Specialized cells perform specialized functions in multicellular organisms. Groups of specialized cells cooperate to form a tissue, such as a muscle.
  2. Q: How is a stem cell different from other normal (somatic) cells? A1: A stem cell can divide over and over again. Embryonic stem cells can divide indefinitely in culture. “Adult” stem cells appear when those three distinct layers show up, but they can only divide a limited number of times in culture. A2: Both embryonic and adult stem cells have the potential to differentiate (or mature) into a range of specialized cell types. Adult stem cells are more restricted than embryonic stem cells in what they can become. Which will be more useful for research and medicine has yet to be confirmed. A3: Stem cells can migrate to where they are needed, although other non-stem cells can do this too. Q: How many cell types can embryonic stem cells differentiate into? A1: All of the 200+ mature cell types in the adult body, including all of the types of adult stem cells.
  3. A progenitor cell further differentiates into CLICK! a mature cell type, like the skin cell in green. The stem cell can divide again, CLICK! this time producing a different type of progenitor cell CLICK! which matures into yet another cell type, CLICK! like a neuron in pink. In this way, stem cells can regenerate tissues after injury and maintain healthy cells and cell numbers.
  4. http://www.nature.com/nature/journal/v414/n6859/images/414098ae.2.jpg
  5. Although they are more difficult to obtain than embryonic stem cells, adult stem cells do have therapeutic potential which some of you might have heard about. A well-established adult stem cell therapy is a bone marrow transplant. Bone marrow transplants have been practiced for 40 years as a treatment for diseases of the blood, bone marrow, and certain types of cancer like leukemia. FIRST, a donor’s tissue type is matched with the patient’s tissue type to make sure the patient won’t reject the transplant. NEXT, bone marrow containing hematopoietic (hee-mat-oh-poetic), or blood-forming, stem cells is taken from the donor’s pelvis. THEN, right before the transplant, the recipient patient receives chemotherapy to destroy all of their malignant blood cells. FINALLY, the donor’s stem cells are filtered out and given in a transfusion to the patient, and the cells will find their way to the bone marrow and eventually repopulate the patient’s blood system. Sometimes instead of receiving stem cells from a donor, the patient can receive their own stem cells. Umbilical cord, the tissue connecting baby to mother before birth, is a rich source of hematopoietic (hee-mat-oh-poetic) stem cells. The umbilical cord is usually thrown away after a baby is born, but some people choose to “bank” the umbilical cord blood cells in case the child needs to use those stem cells later on. Hematopoietic stem cells from umbilical cord do not have the same immune-rejection issues as hematopoietic stem cells from bone marrow, which makes them ideal for therapies.
  6. http://newsimg.bbc.co.uk/media/images/45220000/gif/_45220227_961188b5-37a0-4aec-a13d-140e8bc0e7c7.gif
  7. A research study in human beings that follows a pre-defined protocol.