Human Physiology, 14th edition (2016)

Blastocyst cavity

Trophoblast

Inner cell mass

Embryonic pole

Endometrial

epithelium

Endometrial

capillary

Endometrial

gland

(a)

Syncytiotrophoblast

Cytotrophoblast

Amniotic cavity

Embryonic disc

(b)

Reproduction 739

Many people hope that ES cells produced in this way might
be induced to differentiate into dopamine-releasing neurons for
the treatment of Parkinson’s disease, other neurons for the treat-
ment of spinal cord injuries, insulin-secreting beta cells for the
treatment of type 1 diabetes mellitus, and other cell types for
treating diseases that are presently incurable. A patient would not
immunologically reject these cells if they were derived using the
patient as the donor of the nucleus for the somatic cell nuclear
transfer. However, in the first therapeutic use of ES cells, patients
with spinal cord injury will receive oligodendrocyte precursor
cells developed from one of the original embryonic stem cell
lines, and thus will need drugs to suppress immunological rejec-
tion of these cells.
In contrast to ES cells, adult stem cells are found in pro-
tected locations where renewal of specialized cells is required
in the adult body. For example, neural stem cells are located in
the hippocampus (chapter 8; see fig. 8.15) and subventricular
zone of the brain; epithelial stem cells are found in the intesti-
nal crypts (chapter 18; see fig. 18.10) and in the bulge of hair
follicles (chapter 1; see fig. 1.23); and hematopoietic stem cells
are found in the bone marrow (chapter 13; see fig. 13.4).
Adult stem cells have been described as multipotent, because
they can give rise to a number of differentiated cell types. For
example, neural stem cells give rise to neurons and glial cells, and
hematopoietic stem cells give rise to different types of blood cells.
In general, adult stem cells are believed to differentiate into cells
characteristic of their organ, and do not jump across embryonic
germ layer (embryonic tissue) lines. Adult stem cells may have
some flexibility within the constraints of the embryonic germ lay-
ers, such as changing from bone marrow tissue to muscle tissue
(because both are derived from mesoderm). For example, stem
cells from the bone marrow can differentiate into myocardial cells,

which may help repair myocardial infarction, and into skeletal

muscle fibers, which may be useful in the treatment of muscular

dystrophy. There are also some stem cells in the heart, which nor-

mally replace about 1% of myocardial cells per year but are insuffi-

cient to repair a myocardial infarction. These have been multiplied

in vitro and introduced into heart patients with some success.

Part of the 2012 Nobel Prize in Physiology or Medicine was

awarded to Shinya Yamanaka for pioneering work first published

in 2006. He and his colleagues demonstrated that adult human

fibroblasts could be changed into pluripotent stem cells by using

retroviruses (similar to HIV; see chapter 15, section 15.3) to insert

into the cell’s DNA four human genes coding for transcription fac-

tors. Transcription factors, as described in chapter 3, section 3.3,

are proteins that regulate the transcription of specific genes. The

four transcription factors reprogrammed the cells into what these

scientists called induced pluripotent stem ( iPS ) cells.

This important discovery has produced a great deal of

excitement, because iPS cells could be used to (1) generate

many cell lines with different diseases, so that the mechanisms

of the diseases can be studied; (2) test how different drugs

work on those diseases; (3) test the effectiveness and toxic-

ity of drugs on cells from people with genetic differences; and

(4) produce stem cells that can be used to treat many diseases.

Use of iPS cells to treat specific diseases, including sickle-cell

anemia and Parkinson’s disease, has been successful in mice,

and an attempt to treat macular degeneration with iPS cells in

humans may soon be made.

A field called regenerative medicine involves developing

future medical treatments using stem cells. Embryonic stem

cells, derived using a patient’s nucleus inserted into an unfertil-

ized oocyte’s cytoplasm (the technique of somatic cell nuclear

transfer, previously discussed), can develop into tissues tolerated

Figure 20.43 Implantation of the blastocyst. ( a ) A diagram showing the blastocyst attached to the endometrium on about
day 6. ( b ) Implantation of the blastocyst at day 9 or 10.