Preclinical safety studies of human embryonic stem cell-derived retinal pigment epithelial cells for the treatment of age-related macular degeneration

Autor: Monica Aronsson, Anders Kvanta, Pankaj Kumar, Sara Padrell Sánchez, Fredrik Lanner, Helder André, Alvaro Plaza Reyes, Hammurabi Bartuma, Sandra Petrus-Reurer, Emeline F. Nandrot
Přispěvatelé: Karolinska Institutet [Stockholm], Institut de la Vision, Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), Nandrot, Emeline, Centre National de la Recherche Scientifique (CNRS)-Sorbonne Université (SU)-Institut National de la Santé et de la Recherche Médicale (INSERM)
Rok vydání: 2020
Předmět:
Pluripotent Stem Cells
0301 basic medicine
Human Embryonic Stem Cells
Cell
retinal pigment epithelium
Biology
chemically defined
Germline
Manufacturing for Regenerative Medicine
Cell therapy
Macular Degeneration
03 medical and health sciences
xeno‐free
0302 clinical medicine
medicine
Humans
lcsh:QH573-671
[SDV.MHEP.OS]Life Sciences [q-bio]/Human health and pathology/Sensory Organs
Induced pluripotent stem cell
biodistribution
ComputingMilieux_MISCELLANEOUS
Aged
lcsh:R5-920
whole genome sequencing
Retinal pigment epithelium
lcsh:Cytology
age‐related macular degeneration
Cell Differentiation
cellular therapy
Cell Biology
General Medicine
Macular degeneration
medicine.disease
Embryonic stem cell
In vitro
3. Good health
030104 developmental biology
medicine.anatomical_structure
[SDV.MHEP.OS] Life Sciences [q-bio]/Human health and pathology/Sensory Organs
Cancer research
tumorigenicity
lcsh:Medicine (General)
safety studies
subretinal injection
030217 neurology & neurosurgery
Developmental Biology
Zdroj: Stem Cells Translational Medicine
Stem Cells Translational Medicine, 2020, 9, pp.936-953. ⟨10.1002/sctm.19-0396⟩
Stem Cells Translational Medicine, Vol 9, Iss 8, Pp 936-953 (2020)
Stem Cells Translational Medicine, Wiley, 2020, 9, pp.936-953. ⟨10.1002/sctm.19-0396⟩
ISSN: 2157-6580
2157-6564
DOI: 10.1002/sctm.19-0396
Popis: As pluripotent stem cell (PSC)‐based reparative cell therapies are reaching the bedside, there is a growing need for the standardization of studies concerning safety of the derived products. Clinical trials using these promising strategies are in development, and treatment for age‐related macular degeneration is one of the first that has reached patients. We have previously established a xeno‐free and defined differentiation protocol to generate functional human embryonic stem cells (hESCs)‐derived retinal pigment epithelial (RPE) cells. In this study, we perform preclinical safety studies including karyotype and whole‐genome sequencing (WGS) to assess genome stability, single‐cell RNA sequencing to ensure cell purity, and biodistribution and tumorigenicity analysis to rule out potential migratory or tumorigenic properties of these cells. WGS analysis illustrates that existing germline variants load is higher than the introduced variants acquired through in vitro culture or differentiation, and enforces the importance to examine the genome integrity at a deeper level than just karyotype. Altogether, we provide a strategy for preclinical evaluation of PSC‐based therapies and the data support safety of the hESC‐RPE cells generated through our in vitro differentiation methodology.
Retinal pigment epithelial cells derived from human embryonic stem cells are a promising source for replacement therapy in age‐related macular degeneration. However, preclinical studies concerning safety of the derived products are indispensable. Here, we evaluate safety invitro and invivo, reassuring stability, purity, and lack of tumorigenicity or migratory potential of the derived product for safe clinical translation.
Databáze: OpenAIRE
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