Pluripotent stem cells progressing to the clinic

Abstract

Basic experimental stem cell research has opened up the possibility of many diverse clinical applications; however, translation to clinical trials has been restricted to only a few diseases. To broaden this clinical scope, pluripotent stem cell derivatives provide a uniquely scalable source of functional differentiated cells that can potentially repair damaged or diseased tissues to treat a wide spectrum of diseases and injuries. However, gathering sound data on their distribution, longevity, function and mechanisms of action in host tissues is imperative to realizing their clinical benefit. The large-scale availability of treatments involving pluripotent stem cells remains some years away, because of the long and demanding regulatory pathway that is needed to ensure their safety.

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Figure 1: The leading applications for pluripotent stem cell derivatives.
Figure 2: The bench to bedside pathway.
Figure 3: The translation pathway for product development and interactions with regulatory agencies.

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Correspondence to Alan Trounson.

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Competing interests

A.T. declares competing financial interests as a Board Director of Stem Cells Inc., California, USA, and Cartherics Pty Ltd., Australia.

PowerPoint slides

Glossary

Allogeneic therapies

Transplants using cells or tissues derived from a different person.

Autologous therapies

Immunologically compatible transplants using the patient's own cells or tissues.

A9 dopaminergic neurons

Mature dopamine-producing neurons of the midbrain substantia nigra, which are lost in Parkinson disease.

Choroid

Vascular layer of the eye between the retina and the sclera.

Cell-mediated immune rejection

Activation of the innate immune system in response to cells recognized as foreign, which can constitute a major barrier to successful organ transplantation and allogeneic cell therapies.

Dyskinesia

Repetitive, involuntary and purposeless movements.

Expandable (immortal) in culture

Capable of continuous cell replication and passage in vitro without senescence.

Graft-versus-host disease

(GVHD). When the immune cells of a foreign transplant attack the recipient's own tissues, causing serious life-threatening loss of organ or tissue function.

Housekeeping genes

Constitutive genes that are responsible for the maintenance of basic cell function and are normally expressed in all cells.

Humanized mice

Genetically modified mice with human immune cells that are tolerant to human grafts.

Immune-competent humans

Humans with natural uncompromised immunity.

Immune-incompetent mice

Mice that are genetically modified to prevent the development of an adaptive immune system.

Infarct

An area of tissue death or necrosis caused by lack of local oxygen due to blockage of blood supply.

Knock-in gene mutants

Cells or organisms with gene and regulatory DNA elements introduced into their genomes to enable expression of an introduced mutant gene.

Macula

An oval-shaped area near the centre of the retina of the eye, specialized for high-acuity vision.

Oligodendrocyte

Glial cell of the central nervous system (CNS) that is responsible for creating the myelin sheath surrounding the axons of CNS neurons, enabling transmission of electronic impulses.

Optogenetic

Light-directed identification and control of individual neurons, in living tissue, that have been genetically modified to express light-sensitive ion channels.

Pharmacogenetic

Drug-directed control of individual neurons that have been genetically modified to respond to specific drugs.

Teratomas

Tumours with organ and tissue components that are derivatives of more than one germ layer, typically formed in vivo from pluripotent stem cells.

Tissue stem cell

Undifferentiated stem cell in a tissue or organ that can self-renew and give rise to the major cell types of that tissue or organ. Tissue stem cells are also referred to as adult stem cells or somatic stem cells.

Ventricular arrhythmias

Severely abnormal heart rhythms that cause the majority of sudden deaths due to heart problems.

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Trounson, A., DeWitt, N. Pluripotent stem cells progressing to the clinic. Nat Rev Mol Cell Biol 17, 194–200 (2016). https://doi.org/10.1038/nrm.2016.10

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