Robust strategies have been developed to differentiate pluripotent stem cells into retinal
pigment epithelium, A9 dopaminergic neurons, oligodendrocyte, pancreatic β-islet cells
and cardiomyocytes. Clinical trials are underway for embryonic stem cell (ES cell)
derivatives for age-related macular degeneration (AMD), type I diabetes, spinal cord
injury, myocardial infarct and Parkinson disease (using parthenogenetic embryonic stem
cells (pES cells)).
Induced pluripotent stem cells (iPSCs) are in a clinical trial for AMD. Rigorously tested,
abundant sources of these cell types are needed for preclinical research to generate
data for regulatory approval for human studies. The cells also need to be manufactured
in large quantities for clinical trials.
These clinical studies in humans begin with regulatory approval for Phase I trials, which
demonstrate safety. They are followed by Phase II studies showing proof of concept for
cell therapy in human patients. Sometimes, Phase I–II studies are designed to
demonstrate both safety and efficacy. Larger-scale Phase III clinical trials aim to
demonstrate the statistical significance of the therapeutic benefit.
Diagram of the evolving clinical trials process and other mechanisms of therapy
translation to the bedside. The traditional, multi-phasic FDA clinical trials process is
shown in black with a black arrow from bench to bedside. Evolving FDA mechanisms for
accelerating the clinical trial process are shown in orange. Compassionate Use (also
known as “Expanded Access”) and Right To Try (RTT) are shown in green with a loop
reflecting the bypassing of Phase 2 and Phase 3. It is notable that the requirements for
Compasionate Use are evolving and there are diverse stakeholder views. The precise
pre-requisites (e.g. Phase 1 versus Phase 2 data) obtainable from FDA guidance are not
completely clear and may vary on a case-by-case basis. The common stem cell clinic
approach of entirely avoiding the clinical trials approval process is shown in red. Note
that for some non-more than minimally manipulated stem cell products used in a
homologous manner, direct use by stem cell clinics or other physicians may be
appropriate with only a relatively minor role for the FDA.
Updated data from 23/2/2018 – compared to 22/2/2019
https://clinicaltrials.gov/ct2/results?term=heart+failure+human+embryonic
https://clinicaltrials.gov/ct2/show/NCT02057900?term=heart+failure+human+embryoni
c&rank=1 PATCH – ESCORT study est JUNE 2018
http://www.onlinejacc.org/highwire/markup/28281/expansion?width=1000&height=50
0&iframe=true&postprocessors=highwire_figures%2Chighwire_math%2Chighwire_inline
_linked_media%2Chighwire_embed
https://clinicaltrials.gov/ct2/results?term=heart+human+induced+pluripotent&type=&rs
lt=&recr=&age_v=&gndr=&cond=&intr=&titles=&outc=&spons=&lead=&id=&state1=&c
ntry1=&state2=&cntry2=&state3=&cntry3=&locn=&rcv_s=&rcv_e=&lup_s=&lup_e=
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P. Menasch´e, O. Alfieri, S. Janssens et al., “The myoblast
autologous grafting in ischemic cardiomyopathy (MAGIC)
trial: first randomized placebo-controlled study of myoblast
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D. M. Leistner, U. Fischer-Rasokat, J. Honold et al., “Transplantation
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Long-term results of intracoronary bone marrow cell transplantation: the potential of
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Meluzín J, Mayer J, Groch L, Janousek S, Hornácek I, Hlinomaz O, Kala P, Panovský R,
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J. M. Hare, J. E. Fishman, G. Gerstenblith et al., “Comparison of allogeneic vs autologous
bonemarrow-derivedmesenchymal stem cells delivered by transendocardial injection in
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The TRansendocardial Stem Cell Injection Delivery Effects on Neomyogenesis STudy (The
TRIDENT Study) (Trident) (NCT02013674)
E. C. Perin, R. Sanz-Ruiz, P. L. S´anchez et al., “Adipose-derived regenerative cells in
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R. Bolli, A. R. Chugh, D. D’Amario et al., “Cardiac stem cells in patients with ischaemic
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Derivation of Human Induced Pluripotent Stem (iPS) Cells to Heritable Cardiac
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“Blood Collection From Healthy Volunteers and Patients forthe Production of
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