What is the current clinical usefulness of stem cell

treatments, embryonic and IPS cells?

Human adult stem cells (iPS) have been found to be most clinically useful human cells for
therapeutic purposes

Pluripotent cells (PCs) are defined as those from which cells of different tissue types can be obtained.
These can be obtained either from preimplantation human embryonic cells, in which case pluripotent
embryonic stem cells are obtained, or from somatic (adult) cells that can be reprogrammed to a state
of pluripotentiality, called induced pluripotent cells (iPS cells).
Ad present stem cell treatments with human adult stem cells have been found to be most clinically
useful human cells for therapeutic purposes, especially cells from bone marrow, peripheral blood,
umbilical cord blood or other tissues. Mesenchymal cells obtained from bone marrow, placenta and
the umbilical cord are particularly useful. These cells have the advantage of having low
immunogenicity and the disadvantage that after being transplanted, they persist for very little time in
the recipient, which poses problems for maintaining their effect over time. These cells can be
obtained from the patients themselves or from external donors, which gives rise to autologous
therapy (which uses cells from the patient themselves) or allogenic therapy (which uses cells from
individuals other than the patient). Their use has so far given good results as regards their safety,
which has been evaluated in very diverse clinical trials. However, pluripotent cells, both embryonic
and iPS cells, have limited clinical applications as they have been used in little more than ocular
diseases. Therefore, it is of no interest to analyse this clinical usefulness at present, following a
magnificent review recently published in Nature Reviews/Molecular Cell Biology (17; 194-200, 2016).

Spinal cord injuries

Spinal cord injuries, most often traumatic, cause paraplegia in patients who suffer them, hence the
importance of being able to treat them.
 Studies to date have always been in the experimental area, with rats and mice, in which recovery of
feet and tail movements has been confirmed in the injured animals. However, these data, well
documented in rodents, have not been proven in humans, with the exception of a patient whose
spinal cord was severely damaged with a knife. Two companies — Geron and Asteria — hope to
commence clinical trials in humans.

Neurodegenerative diseases

1. Huntington’s disease. Essentially characterised by loss of the sheath that protects the neurons. To
date, nerve cells with their accompanying sheath have been produced from iPS cells, but much
larger studies are required to test their therapeutic efficacy.
2. Parkinson’s disease. As we know, this disease is due to a reduction in the proportion of dopamine-
producing neurons, i.e. dopaminergic neurons. Although positive results have been obtained in
rodents, in which the clinical symptoms of Parkinson’s were reduced, their clinical effect is not as
evident in humans. A phase I clinical trial has been approved in Australia using embryonic
pluripotent cells from embryos obtained by parthenogenesis. Some clinical experiments have also
been carried out in mice and monkeys to check whether there is any clinical improvement in these
animals. However, some technical aspects, particularly the purity of the transplanted material,
must be improved before they can be used in humans.
3. Amyotrophic lateral sclerosis (ALS). ALS is a fatal disease characterised by progressive loss of
neurocellular activity, leading to gradual loss of motor neurons. We know that motor neurones are
maintained functionally active by another type of neurons, the astrocytes, so the use of the latter
in phase 1 and 2 clinical trials could be interesting for the treatment of ALS. However, since the
mechanisms of this disease are not well known, studies have so far failed to achieve steady
recovery of damaged motor neurons. (Read last advace HERE)

Eye diseases

The area of ocular disease is the medical field where the most positive steps have been taken for the
use of iPS cells (read more HERE), especially in age-related macular degeneration and Stargardt’s
disease. Age-related macular degeneration is the most common cause of blindness in the over-60s.
This disease leads to progressive loss of epithelium from the retina, affecting its photoreceptors and
thus producing blindness.
To date, only preclinical studies in animals have been conducted, but a clinical trial was recently
started in patients with age-related macular degeneration, using iPS cells derived from the patients’
own somatic cells. The first patient obtained encouraging results, in that there seemed to be no
negative side effects and he obtained some improvement in his visual deficit. However, alterations
were found in the genome of the second patient, derived from the reprogramming process, which led
to the trial being halted by the Japanese health authorities. Therefore as far as we are aware, there
are no ongoing human clinical trials at present.

Diabetes

Although there are positive preclinical studies for treating diabetes in animals with iPS cells, in the
clinical area there is only one phase 1 and 2 ongoing multicentre clinical trial sponsored by the
company ViaCyte. The procedure involves using a subcutaneous encapsulation medical device to
treat patients with type 1 diabetes (last advance read HERE)
Heart disease

Recent studies have shown that heart cells derived from human embryonic stem cells can improve
deteriorated cardiac function in animal models, but in the human setting we are aware of only one
patient in which heart cells derived from human embryonic stem cells were implanted the infarcted
area in parallel with a by-pass procedure. Although no adverse effects were recorded, and cardiac
function appears to have improved at three months, the possibility of obtaining positive clinical
results remains distant (read an example of the possible use of iPS cellsHERE).

Future outlook

According to most experts, although clinical trials using cells obtained from embryonic stem cells or
iPS cells have been proposed and are ongoing, it is generally agreed that it will still be a few years
before these cells are really useful for human medicine.

Justo Aznar

Bioethics Observatory

Catholic University of Valencia