Prospects for clinical use of reprogrammed cells for autologous treatment of macular degeneration

Abstract

Since the discovery of induced pluripotent stem cells (iPSC) in 2006, the symptoms of many human diseases have been reversed in animal models with iPSC therapy, setting the stage for future clinical development. From the animal data it is clear that iPSC are rapidly becoming the lead cell type for cell replacement therapy and for the newly developing field of iPSC-derived body organ transplantation. The first human pathology that might be treated in the near future with iPSC is age-related macular degeneration (AMD), which has recently passed the criteria set down by regulators for phase I clinical trials with allogeneic human embryonic stem cell-derived cell transplantation in humans. Given that iPSC are currently in clinical trial in Japan (RIKEN) to treat AMD, the establishment of a set of international criteria to make clinical-grade iPSC and their differentiated progeny is the next step in order to prepare for future autologous cell therapy clinical trials. Armed with clinical-grade iPSC, we can then specifically test for their threat of cancer, for proper and efficient differentiation to the correct cell type to treat human disease and then to determine their immunogenicity. Such a rigorous approach sets a far more relevant paradigm for their intended future use than non-clinical-grade iPSC. This review focuses on the latest developments regarding the first possible use of iPSC-derived retinal pigment epithelial cells in treating human disease, covers data gathered on animal models to date and methods to make clinical-grade iPSC, suggests techniques to ensure quality control and discusses possible clinical immune responses.

In Pursuit of Authenticity: Induced Pluripotent Stem Cell-Derived Retinal Pigment Epithelium for Clinical Applications

“…Induced pluripotent stem cells (iPSCs) are a valuable source for generating retinal pigment epithelium (RPE) for transplantation to alleviate visual impairment associated with age‐related macular degeneration, a disease that afflicts 20 to 25 million people worldwide [1, 2]. On the basis of pioneering work done with in vitro RPE differentiation and with surgical techniques to transplant RPE monolayers in the eye [3–6], pluripotent stem cell‐derived RPE is considered an ideal target for the development and optimization of stem cell therapy. However, generating stem cell‐based therapy requires well‐defined and authenticated iPSC‐RPE [7].…”

The Application of Human iPSCs in Neurological Diseases: From Bench to Bedside

“…The hematopoietic stem cells have already been used in clinic to treat disease such as multiple myeloma and leukemia [ 54 ]. Recently, Japanese scientists applied human iPSCs in curing ophthalmological diseases in real patients [ 55 ]. It has also been well envisioned that in the near future we can have human iPSC derived organs for transplantation surgery [ 56 ].…”

“…A mature transplantation protocol for PD treatment should not only address the safety issues discussed above but also refine an optimal differentiation protocol to ensure proper cell identities and long-term functions [ 98 – 100 ]. Hopefully, lessons and progress learned from clinical trials using iPSC products in other diseases can lend some useful experience [ 55 , 86 ].…”

Global Proteomic and Methylome Analysis in Human Induced Pluripotent Stem Cells Reveals Overexpression of a Human TLR3 Affecting Proper Innate Immune Response Signaling

“…A recent review identified that many aspects of the adaptive and innate immune system mechanisms are yet to be explored in detail for human cells . Data from human transplanted autologous reprogramed cells in vivo is limited and only one current clinical trial for iPSC‐RPE cells exists that found edema in the patient retina most likely from the surgical intervention for the transplanted iPSC‐RPE cell sheet . As the field grows and moves closer to clinical application the need to understand the extent of the immune response to transplanted human iPSC‐derived cells becomes paramount.…”