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 controlsStabilize 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 Division1. 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/ligamentNeural stem cells: neurons, glial cellsEpithelial 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 TherapiesBone 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