2. Academic Validation
  3. Clinically compliant cryopreservation of differentiated retinal pigment epithelial cells

Clinically compliant cryopreservation of differentiated retinal pigment epithelial cells

  • Cytotherapy. 2024 Feb 13:S1465-3249(24)00046-X. doi: 10.1016/j.jcyt.2024.01.014.
Laura Baqué-Vidal 1,  Heather Main 1,  Sandra Petrus-Reurer 2,  Alex R Lederer 3,  Nefeli-Eirini Beri 1,  Frederik Bär 1,  Hugo Metzger 1,  Cheng Zhao 1,  Paschalis Efstathopoulos 4,  Sarah Saietz 1,  Andreas Wrona 4,  Elham Jaberi 4,  Hanni Willenbrock 4,  Hazel Reilly 1,  Mona Hedenskog 1,  Elisabeth Moussaud-Lamodière 1,  Anders Kvanta 5,  J Carlos Villaescusa 4,  Gioele La Manno 3,  Fredrik Lanner 6
Affiliations

Affiliations

  • 1 Department of Clinical Science, Intervention and Technology (CLINTEC), Karolinska Institutet, Stockholm, Sweden; Division of Obstetrics and Gynecology, Karolinska Universitetssjukhuset, Stockholm, Sweden.
  • 2 Department of Clinical Science, Intervention and Technology (CLINTEC), Karolinska Institutet, Stockholm, Sweden; Division of Obstetrics and Gynecology, Karolinska Universitetssjukhuset, Stockholm, Sweden; Department of Clinical Neuroscience, Division of Eye and Vision, St. Erik Eye Hospital, Karolinska Institutet, Stockholm, Sweden; Department of Surgery, University of Cambridge, NIHR Cambridge Biomedical Research Centre, Cambridge, UK.
  • 3 Laboratory of Neurodevelopmental Systems Biology, Brain Mind Institute, School of Life Sciences, École Polytechnique Fédérale de Lausanne (EPFL), Lausanne, Switzerland.
  • 4 Cell Therapy R&D, Novo Nordisk A/S, Måløv, Denmark.
  • 5 Department of Clinical Neuroscience, Division of Eye and Vision, St. Erik Eye Hospital, Karolinska Institutet, Stockholm, Sweden.
  • 6 Department of Clinical Science, Intervention and Technology (CLINTEC), Karolinska Institutet, Stockholm, Sweden; Division of Obstetrics and Gynecology, Karolinska Universitetssjukhuset, Stockholm, Sweden; Ming Wai Lau Center for Reparative Medicine, Karolinska Institutet, Stockholm, Sweden. Electronic address: Fredrik.lanner@ki.se.
PMID: 38349309 DOI: 10.1016/j.jcyt.2024.01.014
Abstract

Background aims: Age-related macular degeneration (AMD) is the most common cause of blindness in elderly patients within developed countries, affecting more than 190 million worldwide. In AMD, the retinal pigment epithelial (RPE) cell layer progressively degenerates, resulting in subsequent loss of photoreceptors and ultimately vision. There is currently no cure for AMD, but therapeutic strategies targeting the Complement System are being developed to slow the progression of the disease.

Methods: Replacement therapy with pluripotent stem cell-derived (hPSC) RPEs is an alternative treatment strategy. A cell therapy product must be produced in accordance with Good Manufacturing Practices at a sufficient scale to facilitate extensive pre-clinical and clinical testing. Cryopreservation of the final cell product is therefore highly beneficial, as the manufacturing, pre-clinical and clinical testing can be separated in time and location.

Results: We found that mature hPSC-RPE cells do not survive conventional cryopreservation techniques. However, replating the cells 2-5 days before cryopreservation facilitates freezing. The replated and cryopreserved hPSC-RPE cells maintained their identity, purity and functionality as characteristic RPEs, shown by cobblestone morphology, pigmentation, transcriptional profile, RPE markers, transepithelial resistance and pigment epithelium-derived factor secretion. Finally, we showed that the optimal replating time window can be tracked noninvasively by following the change in cobblestone morphology.

Conclusions: The possibility of cryopreserving the hPSC-RPE product has been instrumental in our efforts in manufacturing and performing pre-clinical testing with the aim for clinical translation.

Keywords

age-related macular degeneration; clinical translation; cryopreservation; manufacturing; retinal pigment epithelium.

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