This has set a standard what these optimal cells can do [6C9]. Rabbit Polyclonal to CSRL1 cells, rescue of the host retina, and improvement of visual function. Based on the positive results obtained from these animal experiments, human clinical trials are being initiated. Despite such progress in stem cell research, ethical, regulatory, security, and technical troubles still remain a challenge for the transformation of this technique into a standard clinical approach. In this review, the current status of preclinical security and efficacy studies for retinal cell replacement therapies conducted in animal models will be discussed. 1. Introduction Stem cell-based therapies have shown to restore or rescue visual function in preclinical models of retinal degenerative diseases [1C5] which are built on previous data with transplantation of fetal retinal tissue linens. This has set a standard what these optimal cells can do [6C9]. Although retinal degenerative diseases such as retinitis pigmentosa (RP), age-related macular degeneration (AMD), and Stargardt’s disease differ in their causes and demographics, all of them cause RPE and/or photoreceptor destruction which can lead to blindness [1C5]. Currently, there is no clinically accepted remedy for irreversible dysfunction or death of photoreceptors and RPE. Since the retina, like other central nervous system tissue, has little regenerative potential [4, 10], stem cell-based therapies that aimed to replace the dysfunctional or lifeless cells remain a major hope. In 1959, a rat fetal retina was transplanted into the anterior chamber of a pregnant rat’s vision [11]. Several decades later, dissociated retinal cells or cell aggregates were transplanted into the subretinal space of rats [12C17]. In the 80s, Dr. Gouras exhibited transplantation of cultured human retinal pigment epithelial cells into the monkey retina. The transplanted cells were identified around the Bruch’s membrane by Fulvestrant R enantiomer autoradiography [18]. Turner and Blair reported high survival (90C100%) and development of lamination for newborn rat retinal aggregates grafted into a lesion site of an adult rat retina [19]. Silverman and Hughes were the first one to isolate stripes of photoreceptor linens from your postnatal and adult retina [20], and this method was altered later on by other experts by transplanting photoreceptor linens [21], full thickness fetal [6, 7, 22C24] or adult retina [25]. These earlier transplantation studies helped to establish proof of concept for future cell replacement therapies in the eye. Although the initial transplantation studies did not show any security issues, ethical restrictions and Fulvestrant R enantiomer absence of suitable animal models for preclinical evaluations delayed further progress of this approach [3]. In 2009 2009, human embryonic stem cell- (hESC-) derived RPE cells were transplanted into Royal College of Doctor (RCS) rats in preclinical studies [26] that eventually lead to clinical trials. Even though long-term outcomes of the preclinical investigations are not yet concluded [27C31], recent advancement in the area of induced pluripotent stem cell- (iPSC-) derived products provided a new source for transplantation. This method uses mature cells that return to a pluripotent state similar to that seen in embryonic stem cells [32C35]. Preclinical screening of iPSC-derived RPE (iPSC-RPE) cells has been established [36, 37], and human clinical trials based on iPSC-RPE have been initiated [38]. These studies indicate Fulvestrant R enantiomer survival of the transplanted RPE with indicators of visual functional improvement and no indicators of adverse events. However, one of the first human clinical trials using autologous iPSC-RPE cells lead by Masayo Takahashi was halted for a period of time after unexpected chromosomal abnormalities were found in the second patient [39, 40]. In a different incident, severe vision loss was observed in three AMD patients after intravitreal injection of autologous adipose tissue-derived stem cells (https://blog.cirm.ca.gov/2017/03/15/three-people-left-blind-by-florida-clinics-unproven-stem-cell-therapy/comment-page-1/). The above report raises some concerns regarding the existing security requirements and regulations of the use of unregulated stem cell trials [41]. In this review, current progress in stem cell-based therapies will be discussed based on security assessments and functional evaluations conducted in various animal models of human retinal degenerative diseases. 2. Stem Cell Sources and Their Applications in the Eye Stem cell-based therapy for RPE replacement has been initiated at numerous centers. Since Klimanskaya et al. developed the original protocol for hESC-derived RPE-like cells [42], numerous groups have used several strategies to derive RPE cells from stem cells. In earlier studies, subretinal transplantation of hESC-derived RPE (hESC-RPE) cells based on.
This has set a standard what these optimal cells can do [6C9]
