Human embryonic and induced pluripotent stem cells in clinical trials: Table 1

The production of human induced pluripotent stem cells (hiPSCs) in quantities that are relevant for cell-based therapies and cell-loaded implants through standard adherent culture is hardly achievable and lacks process scalability. A promising approach to overcoming these hurdles is the culture of hiPSCs in suspension. In this study, stirred suspension culture vessels were investigated for their suitability in the expansion of two hiPSC lines inoculated as a single cell suspension, with a free scalability between volumes of 50 and 2400 ml. The simple and robust two-step process reported here first generates hiPSC aggregates of 324 ± 71 μm diameter in 7 days in 125 ml spinner flasks (100 ml volume). These are subsequently dissociated into a single cell suspension for inoculation in 3000 ml bioreactors (1000 ml volume), finally yielding hiPSC aggregates of 198 ± 58 μm after 7 additional days. In both spinner flasks and bioreactors, hiPSCs can be cultured as aggregates for more than 40 days in suspension, maintain an undifferentiated state as confirmed by the expression of pluripotency markers TRA-1-60, TRA-1-81, SSEA-4, OCT4, and SOX2, can differentiate into cells of all three germ layers, and can be directed to differentiate into specific lineages such as cardiomyocytes. Up to a 16-fold increase in hiPSC quantity at the 100 ml volume was achieved, corresponding to a fold increase per day of 2.28; at the 1000 ml scale, an additional 10-fold increase was achieved. Taken together, 16 × 10 6 hiPSCs were expanded into 2 × 10 9 hiPSCs in 14 days for a fold increase per day of 8.93. This quantity of hiPSCs readily meets the requirements of cell-based therapies and brings their clinical potential closer to fruition.

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“…The first trial thus far using hiPSCs as the cell source was initiated in Japan in 2013 (Ilic, Devito, Miere, & Codognotto, 2015).…”

mentioning

confidence: 99%

Scalable stirred suspension culture for the generation of billions of human induced pluripotent stem cells using single‐use bioreactors

Kwok

Ueda

Kadari

et al. 2017

J Tissue Eng Regen Med

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“…Geron used hESCs for treatment of spinal cord injuries, however, this trial was prematurely halted [60]. Current trials are underway for the treatment of Stargardt's macular dystrophy, dry age-related macular dystrophy and diabetes [60,61].…”

Section: Human Escsmentioning

confidence: 99%

“…The successful implantation of iPSC-derived retinal pigment epithelium cells into a patient with age-related macular dystrophy was reported; however, the trial was prematurely suspended when it was found that the second patient's differentiated cells contained multiple mutations [60]. This raises important safety concerns.…”

Section: Induced Pscsmentioning

confidence: 99%

See 1 more Smart Citation

Augmentation of Musculoskeletal Regeneration: Role for Pluripotent Stem Cells

2018

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The rise in the incidence of musculoskeletal diseases is attributed to an increasing ageing population. The debilitating effects of musculoskeletal diseases, coupled with a lack of effective therapies, contribute to huge financial strains on healthcare systems. The focus of regenerative medicine has shifted to pluripotent stem cells (PSCs), namely, human embryonic stem cells and human-induced PSCs, due to the limited success of adult stem cell-based interventions. PSCs constitute a valuable cell source for musculoskeletal regeneration due to their capacity for unlimited self-renewal, ability to differentiate into all cell lineages of the three germ layers and perceived immunoprivileged characteristics. This review summarizes methods for chondrogenic, osteogenic, myogenic and adipogenic differentiation of PSCs and their potential for therapeutic applications.

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“…The properties and the importance of human embryonic stem cells for potential medical therapies has been discussed previously and reported on in great detail; readers should refer to the relevant literature for more information on this point [9,10]. Moreover, the medical benefits are irrelevant for the observations discussed below.…”

mentioning

confidence: 99%

Response to: Dittrich et al.: Non-Embryo-Destructive Extraction of Pluripotent Embryonic Stem Cells – Overlooked Legal Prohibitions, Professional Legal Consequences and Inconsistencies in Patent Law

Faltus

Storz

2016

Geburtshilfe Frauenheilkd

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Humane embryonale Stammzellen erfahren in der Forschung Interesse für die Entwicklung neuer regenerativmedizinischer Therapien. Allerdings wird, hier am Beispiel für Deutschland gezeigt, selbst frühen Embryonen, die für die Stammzellengewinnung benötigt werden, von verschiedenen Seiten her der grundgesetzlich gesicherte Schutz der Menschenwürde und der Schutz der körperlichen Unversehrtheit zuerkannt. Die Gewinnung und Verwendung humaner embryonaler Stammzellen beschäftigt daher seit deren ersten Gewinnung und Kultivierung [2] sowohl den medizinisch-naturwissenschaftlichen als auch ethischen und rechtlichen Diskurs. Kern dieser Diskussionen war und ist der mora-lische und der damit verbundene rechtliche Status menschlicher Embryonen im Blastozystenstadium. Hier stehen sich im Wesentlichen zwei Positionen gegenüber. Zum einen wird vertreten, dass mit der befruchteten Eizelle, spätestens mit dem Verschmelzen des mütterlichen und väterlichen Kerns, eine Entität mit eigenem moralischen und rechtlichen Wert entstanden ist, wobei dieser Wert dem eines (geborenen) Menschen entspricht, sodass alle Entwicklungsphasen ab dieser Verschmelzung auch rechtlich wie geborene Menschen gegen fremdbestimmte und fremdnützige, weil nicht dem Embryo dienend, Zerstörung oder Verzwecklichung geschützt werden (siehe dazu mit weiteren Nachweisen [3, 4]). Zum anderen wird davon ausgegangen, dass der Moment der Entstehung dieses eigenständigen mora-Zusammenfassung ! Die Veröffentlichung von Dittrich et al. "Embryonenerhaltende Gewinnung pluripotenter Stammzellen: Implikationen für die regenerative Medizin und die Reproduktionsmedizin" Geburtshilfe und Frauenheilkunde 2015; 75: 1239-1242 [1] stellt die Möglichkeiten dar, die sich durch die embryoerhaltende Gewinnung embryonaler Stammzellen aus menschlichen Blastozysten ergeben können. Die Durchführung der Methode ist jedoch rechtlich und ethisch problematischer als von den Autoren dargestellt und in Deutschland rechtlich verboten. Das von Dittrich et al. erwähnte deutsche Patent DE 10 2004 062 184 zur embryoerhaltenden Gewinnung von Stammzellen steht im Widerspruch zur höherrangigen Rechtsprechung des Europäischen Gerichtshofs. Schließlich ist die von Dittrich et al. vorgeschlagene embryoerhaltende Gewinnung von Stammzellen zu Zwecken der Asservierung dieser Zellen für eventuelle Therapieverwendungen in Deutschland strafbeschwert verboten.

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Human embryonic and induced pluripotent stem cells in clinical trials: Table 1

Cited by 69 publications

References 23 publications

Scalable stirred suspension culture for the generation of billions of human induced pluripotent stem cells using single‐use bioreactors

Scalable stirred suspension culture for the generation of billions of human induced pluripotent stem cells using single‐use bioreactors

Augmentation of Musculoskeletal Regeneration: Role for Pluripotent Stem Cells

Response to: Dittrich et al.: Non-Embryo-Destructive Extraction of Pluripotent Embryonic Stem Cells – Overlooked Legal Prohibitions, Professional Legal Consequences and Inconsistencies in Patent Law

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