Potential of Induced Pluripotent Stem Cells (iPSCs) for Treating Age-Related Macular Degeneration (AMD)

Abstract

The field of stem cell biology has rapidly evolved in the last few decades. In the area of regenerative medicine, clinical applications using stem cells hold the potential to be a powerful tool in the treatment of a wide variety of diseases, in particular, disorders of the eye. Embryonic stem cells (ESCs) and induced pluripotent stem cells (iPSCs) are promising technologies that can potentially provide an unlimited source of cells for cell replacement therapy in the treatment of retinal degenerative disorders such as age-related macular degeneration (AMD), Stargardt disease, and other disorders. ESCs and iPSCs have been used to generate retinal pigment epithelium (RPE) cells and their functional behavior has been tested in vitro and in vivo in animal models. Additionally, iPSC-derived RPE cells provide an autologous source of cells for therapeutic use, as well as allow for novel approaches in disease modeling and drug development platforms. Clinical trials are currently testing the safety and efficacy of these cells in patients with AMD. In this review, the current status of iPSC disease modeling of AMD is discussed, as well as the challenges and potential of this technology as a viable option for cell replacement therapy in retinal degeneration.

Stem cell manipulation, gene therapy and the risk of cancer stem cell emergence

“…Although this procedure did not attempt to restore the vision of the patient, since this is very unlikely, it nevertheless provided an opportunity to monitor side effects, immunogenicity or cancer growth in a human patient. To date it constitutes the first clinical trial on a practical aspect of the iPSCs with a positive outcome, illustrating current hopes in regenerative therapies as evidenced by several other ongoing clinical trials for ARMD treatments using iPSCs or ESCs (118,119). Moreover, new prospects for the treatment of hypertension using iPSCs have recently been described (120).…”

Ips Progression a Decade Devoted

“…Takahashi had claimed to stop the degeneration process and the patient experienced an improvement in vision [126]. The trial was halted due to unexplained mutations observed by Yamanaka in the transplanted RPE and the patients' iPS [126,127]. This trial proved that several safety assays need to be established to validate preclinical studies before they are safe to begin future clinical trials.…”

Cell Therapy for Age-Related Macular Degeneration: A New Vision for the Bone Marrow?

“…Nonetheless, animal studies have been translated into clinical trials of this cell replacement approach, but, so far, with inconclusive results. 3 Additionally, ESC use is fraught with ethical concerns. iPSCs might form teratomas due to incomplete differentiation or spontaneously mutate, which has caused a temporary halt of one clinical trial in Japan.…”

“…Anti-VEGF therapies are fairly efficient at counteracting this neovascularization and are currently the mainstream treatment for wet AMD. 3 However, no treatment has been effective so far for the more common dry form.…”