Stem Cell research

What are stem cells? Stem cells are cells that retain the ability to differentiate into many different types of cells In some systems of the body stem cells exist to repair damage (bone marrow, digestive system) Three distinct characteristics: Unspecialized cells Able to renew themselves through cell division (even after long periods of inactivity) Under certain conditions can become tissue specific cells with specialized functions

Embryonic Stem Cells 3-5 day old embryo, blastocyst, will generate ALL of the specialized cells of the body Embryonic Stem Cells Derived from embryos (most from in vitro clinics that are donated to research) Cells are cultured (grown) in a lab for several months to ensure their sustainability If left to continue to divide, the stem cells will spontaneously begin to differentiate Scientists are still working on directing differentiation into the specific desired cells

Somatic (adult) stem cells Found among differentiated cells in a tissue that can renew itself and differentiate into most or all of the cell types for that tissue or organ Primary role is to maintain or repair damage to the tissue/organ Consider the possibilities of using stem cells for transplant recipients Adult stem cells have been found in: brain, bone marrow, blood vessels, blood, skeletal muscle, skin, teeth, heart, gut, liver, ovarian epithelium and testis

Pathways of adult stem cells Hematopoietic stem cells give rise to all the types of blood cells: red blood cells, B lymphocytes, T lymphocytes, natural killer cells, neutrophils, basophils, eosinophils, monocytes, and macrophages. Mesenchymal stem cells give rise to a variety of cell types: bone cells (osteocytes), cartilage cells (chondrocytes), fat cells (adipocytes), and other kinds of connective tissue cells such as those in tendons. Neural stem cells in the brain give rise to its three major cell types: nerve cells (neurons) and two categories of non-neuronal cells—astrocytes and oligodendrocytes.

Pathways of adult stem cells Epithelial stem cells in the lining of the digestive tract occur in deep crypts and give rise to several cell types: absorptive cells, goblet cells, paneth cells, and enteroendocrine cells. Skin stem cells occur in the basal layer of the epidermis and at the base of hair follicles. The epidermal stem cells give rise to keratinocytes, which migrate to the surface of the skin and form a protective layer. The follicular stem cells can give rise to both the hair follicle and to the epidermis.

transdifferentiation This process takes adult cells and reprograms them into another cell type One experiment took pancreatic cells and “reprogrammed” them to be pancreatic beta-like cells that secrete insulin Beta cells are damaged and no longer work in diabetics Induced Pluripotent Stem Cells (iPSCs) Process of reprogramming adult stem cells to be like embryonic stem cells Still a lot to consider from this field

Remaining questions about adult stem cells How many kinds exist and where are they located in the body? How do they evolve in the adult? How are they maintained? Are they “leftover” embryonic cells? Why do the stem cells remain undifferentiated when the cells around them become specialized? What are the characteristics of the “niche” that control their behavior?

Remaining questions about adult stem cells Do they have the ability to transdifferentiate? Can we control it? What are the factors that control cell proliferation and differentiation? What factors stimulate the stem cells to move to areas of injury and how can this process be enhanced for better healing?

Embryonic vs adult stem cells Embryonic stem cells have the ability to differentiate into any cell of the body (they are pluripotent); Adult stem cells appear to only be able to become the cells necessary for the tissue/organ in which they reside Embryonic stem cells are easier to grow in the laboratory; Isolating adult stem cells is difficult (laboratory procedures for culturing are still being worked out) Expected difference in transplant acceptance/rejection A patient’s own cells would be used for adult stem cells

Induced pluripotent stem cells Characteristics of Pluripotent Stem Cells Express stem cell markers Form tumors containing cells from all three germ layers Able to contribute to cell generation in many different tissues when injected at an early stage of development Useful tool in drug development and modeling of diseases Currently use a virus to induce the cells (currently has been shown to cause cancer)

Potential uses of human stem cells Research the complex events of human development How to turn genes on and off Limit diseases like cancer and birth defects Stem cells can be used to test new drugs/treatments Cancer cell lines are already being used to test anti-tumor medications Cell-based therapies Transplant recipient, Alzheimer’s disease, spinal cord injuries, stroke, burns, heart disease, diabetes, osteoarthritis, rheumatoid arthritis

Keys to success To be useful in transplant therapies, stem cells must be made to: Proliferate extensively and generate sufficient quantities of tissue. Differentiate into the desired cell type(s). Survive in the recipient after transplant. Integrate into the surrounding tissue after transplant. Function appropriately for the duration of the recipient's life. Avoid harming the recipient in any way. Currently, it is anticipated that there is a 1 in 217 chance of needing some form of stem cell therapy in an individual’s lifetime.

Cord blood Cord blood is the blood that is remaining in the umbilical cord and placenta after the baby is born Another option for stem cells (specifically regarding stem cells for blood formation) They differ from stem cells because they are biologically younger than other stem cells Less risk of complications in transplants Immediately accessible (when banked) Freezing them “stops the clock” – protected from stresses of life Collection is simple, safe, and painless

Cord blood Has been used to treat blood disorders, leukemia, and other cancers Researching uses in regenerative medicine Possibly to induce hearing or regenerate cells to repair tissues Patients tend to get less graft verses host disease with cord blood transplants than with bone marrow or peripheral blood transplants

Cord blood Reasons cord blood may not be chosen: Cord blood donations tend to have less cells available for transplant It takes longer for cord blood transplants to engraft (begin growing, creating new blood, and an immune system) Patients cannot get a backup donation from the same source if the cells do not engraft or if the patient has a relapse This is a newer therapy and there is not as much research available showing long term effects

Ethical considerations Stem Cell research opens the door for cloning opportunities Stem Cell manipulation can determine the gender of an embryo Use of oocytes with the nucleus removed as “growing chambers” for the specified tissue may be seen as destruction of a potential human life Current embryonic stem cell research uses cells from the blastocyst stage or an aborted fetus’ cells – again destruction of a potential human life