Stem Cells

What is

The fertilized egg contains totipotent stem cells. Can become any cell in the body. These can be used to make models of disease, such as solid cancers and genetic disorders. You may know the subjects as knockout/transgenic mice.

The inner cell mass of the embryo are pluripotent. They can become any cell except placenta. These tend to form tumors when used.

Any tissue which is constantly renewing contains stem cells. For example, the lining of the GI tract, bone marrow in long bones, and seminiferous epithelium in men. The basal layer of the epidermis will also make replace itself as well as the bulb of hair follicles which can become squamous cells, hair, or sebaceous glands.

Derivation

Adult stem cells (ASCs) are considered multipotent and will form a few cells but not many. Multipotent cells will usually come from a true stem cell, but lose ability as it differentiates (see Hematopoeisis > Blood cell production for examples). They are difficult to identify and locate, but some antibodies will bind to them. If obtained, cloning can be achieved using Somatic Cell Nuclear Transfer (SCNT).

Induced pluripotent stems cells (iPSCs) are adult stem cells which have been converted from multipotent to pluripotent. They are created by using viral vectors to transfect genes into fibroblasts.

Important gene vectors

c-Myc (or LIN-28)
Klf4
Sox2
Oct4

Problems with this method

Retrovirus or adenovirus required
Genes may be oncogenic
Genes may not be controlled (e.g. may form teratomas)
Inserted genes may replace working tumor suppressor genes

Uses of Adult Stem Cells

Source from healthy donor, such as with bone marrow transplants.
Source from same (sick) patient. Will have to be dedifferentiated, modified to form the target cell type, and then reinserted.
Source from another somatic cell (transdifferentiating) and differentiate it directly into the target cell type. For example, taking adipose tissue and turning it directly into pancreatic islets.

These can be used to treat diseases from a single gene malfunction or damage to a single cell type.

Clinical Pearl: Repairing Heart Attacks

Transmyocardial injection: Inject cells directly into area of infarct
Intravenous: Inject cells into the blood stream (less effective)
Intracoronary: Use a catheter to inject stem cells into the left anterior descending (LAD) artery
Direct endocardial: Use a transendocardial catheter to inject stem ells within ventricle if area of infarct penetrates deep into myocardium
Coronary sinus injection: Inject stem cells into vein (avoiding cells getting kicked out from blood pressure)