Developing Cellular Therapies for Retinal Degenerative Diseases

Abstract

Biomedical advances in vision research have been greatly facilitated by the clinical accessibility of the visual system, its ease of experimental manipulation, and its ability to be functionally monitored in real time with noninvasive imaging techniques at the level of single cells and with quantitative end-point measures. A recent example is the development of stem cell-based therapies for degenerative eye diseases including AMD. Two phase I clinical trials using embryonic stem cell-derived RPE are already underway and several others using both pluripotent and multipotent adult stem cells are in earlier stages of development. These clinical trials will use a variety of cell types, including embryonic or induced pluripotent stem cell-derived RPE, bone marrow- or umbilical cord-derived mesenchymal stem cells, fetal neural or retinal progenitor cells, and adult RPE stem cells-derived RPE. Although quite distinct, these approaches, share common principles, concerns and issues across the clinical development pipeline. These considerations were a central part of the discussions at a recent National Eye Institute meeting on the development of cellular therapies for retinal degenerative disease. At this meeting, emphasis was placed on the general value of identifying and sharing information in the so-called "precompetitive space." The utility of this behavior was described in terms of how it could allow us to remove road blocks in the clinical development pipeline, and more efficiently and economically move stem cell-based therapies for retinal degenerative diseases toward the clinic. Many of the ocular stem cell approaches we discuss are also being used more broadly, for nonocular conditions and therefore the model we develop here, using the precompetitive space, should benefit the entire scientific community.

Stem cell based therapies for age-related macular degeneration: The promises and the challenges

“…For example, the International Organization of Standardization certified WAVE Bioreactor is a single-use closed bioreactor system used for the production of clinical-grade T cells and NK cells, and in the Bioreactor, these cells are automatically tested for cytotoxicity, local and acute systemic toxicity, irritation and sensitization, endotoxin, and sterility. Such a system could be adopted for producing stem cell-derived cell products like hESC-RPE and iPSC-RPE (Bharti et al, 2014;Bharti, 2011;Eibl, 2009;Timmins, 2009). A thorough discussion of regulatory and logistic issues of the production of stem cell-derived RPE implants has been published by Bharti et al (Bharti et al, 2014).…”

“…Such a system could be adopted for producing stem cell-derived cell products like hESC-RPE and iPSC-RPE (Bharti et al, 2014;Bharti, 2011;Eibl, 2009;Timmins, 2009). A thorough discussion of regulatory and logistic issues of the production of stem cell-derived RPE implants has been published by Bharti et al (Bharti et al, 2014).…”

“…Thus, rabbits, dogs, monkeys, and pigs (e.g. Yucatan minipigs), all having eye sizes close to the human's, have a possible role in pre-clinical studies on stem cell therapies (Bharti et al, 2014). Despite the limitations for experiments on larger animal eyes (e.g.…”

Let There Be Light: Gene and Cell Therapy for Blindness

“…These recommendations address the most pressing needs for the development and delivery of effective treatments for retinal dystrophies in the next decade. The meeting of the National Eye Institute in collaboration with the National Institutes of Health Center for Regenerative Medicine 132 and the Monaciano Symposium 133 strongly recommended collaborative translational efforts, including the creation of international databases of correlative phenotypegenotype information, standardized protocols and outcome measures, common regulatory protocols, and technology transfer mechanisms. 134 There is a strong conviction that efficient partnerships between academia, industry, funding agencies, and policy makers are needed to translate laboratory discovery into the development of innovative gene and cell therapeutic strategies for the treatment of retinal degeneration.…”

Production de rétinesin vitroà partir de cellules pluripotentes humaines

“…Notons qu'à ce jour, le seul essai clinique autorisé utilisant les cellules iPS concerne la transplantation de cellules de l'EPR chez des patients atteints de DMLA au Japon [7]. Outre son potentiel prometteur en méde-cine régénérative, la génération de ces différents types cellulaires rétiniens offre également l'opportunité d'étudier les mécanismes moléculaires et cellulaires impliqués dans le développement de la rétine humaine (Figure 2).…”