Stem Cells from the Ground Floor. Jonathan Golob Medical Scientist Training Program University of Washington Center for Cardiovascular Biology and Regenerative Medicine Department of Pathology Doctoral Candidate.
Medical Scientist Training Program University of Washington
Center for Cardiovascular Biology and Regenerative Medicine
Department of Pathology Doctoral Candidate
Tissues can repair themselves, filling the void with tough but otherwise non-functional material using the body’s equivalent of duct tape: the scar.What happens when we get injured, or something just wears out?
Immune cells come in and clear away the debris and any infection.
Regeneration is the complete restoration of the original tissue. Damaged tissue is replaced by new functional cells.
either dividing the existing functional cells
A stem cell must make more copies of itself (self-renew) and give rise to more capable offspring (differentiate).
or by activating an adult stem cell population.
The more capable the cell becomes, the fewer types of cells it can become.
During differentiation, cells progress down increasingly restrictive lineages.
Bone, Skin, Tendon, cartilage
(placenta and amnion)
Inner cell mass
(all tissues in the body)
Tubule cell of the kidney
Red Blood Cell
Sperm and Egg
MelanocyteThe inner cell mass gives rise to all the cells in the body.
Time of Gestation
Embryonic Stem Cell
Scientists have figured out how to make inner cell mass cells self-renew in plastic dishes.
A few hundred cells from one embryo can be grown into at least 1.3 × 1031 cells creating a stem cell line.
Eggs collected for in-vitro fertility treatment cannot be easily frozen and stored.
Early embryos created after the combination of sperm and eggs can be frozen.
An excess of embryos are created as the process of egg collection is painful, dangerous and expensive.
For most couples, more embryos are created than are needed to have a desired number of children.
Patient-Specific Stem Cells
BlastocystSomatic cell nuclear transfer is an alternate source of embryonic stem cells
Fusion with patient’s cell
Somatic Cell Nuclear Transfer derived embryonic stem cells avoid immune rejection problems and allow the study of complex genetic diseases.
Active areas of research include:
Directing the differentiation into useful cell types.
Studyingcell types that are difficult to acquire from other sources.
Studying the effect of drugs on human development.
What makes embryonic stem cells different from other stem cells and functional adult cells.
Developing new treatments for common diseases using embryonic stem cell derived cells.
Adult stem cells
Embryonic stem cells
Typically reside in or near their tissue
Created from inner cell mass cells that exist only in very early embryos
Are capable of giving rise to functional cells in their tissue (but not other tissue types)
Are typically found only in tissues that undergo regular turnover.
Are capable of giving rise to all of the cell types in the body including non-regenerative
Can be divided many times (possibly indefinitely) in culture to make many cells.
Decrease in both number and activity as one ages.
Leading Causes of Death in the US (2001)
Approximately one billion heartcells are lost during a serious heart attack. If one survives the initial event, a progressive chronic heart failure often occurs due to the replacement of functional beating heart cells with a tough fibrous scar.
2,016 heart transplants were performed in 2004.
About 2,500Americans die of cardiovascular disease each day.
If all major forms of cardiovascular disease were eliminated, life expectancy would increase by about 7 years.
For tissues incapable of regenerating, we look towards stem cellsas a sourceof functional replacement cells.
Do not exist in adults.Can other tissue’s adult stem cells become heart cells by transdifferentation?
Inner Cell Mass
Despite some early non-reproducable results, adult bone marrow cells cannot become heart, liver or brain cells.
Various labs around the world have described four non-overlapping stem cell populations in the heart.
The data is still very incomplete for each of these cell types.
It is unclear what role, if any, is played by these cells.
An eventual goal is to activate these cells after a heart attack, or somehow augment their function.
Tissues resort to non-functional repair mechanisms when there is a lack of functional replacement cells either due to the properties of the tissue or the endogenous regeneration pathways being overwhelmed.
Embryonic stem cells have an unmatched and undisputed ability to become any cell type found within the body.
Early attempts, using a flawed experimental approach, falsely indicated that bone marrow derived stem cells could become heart cells, against their lineage commitment.