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This study was conducted to determine the dynamic Islet1 and Brn3 (POU4F) expression pattern in the human fetal retina and human-induced pluripotent stem cell- (hiPSC-) derived retinal organoid. Human fetal eyes from 8 to 27 fetal weeks (Fwks), human adult retina, hiPSC-derived retinal organoid from 7 to 31 differentiation weeks (Dwks), and rhesus adult retina were collected for cyrosectioning. Immunofluorescence analysis showed that Islet1 was expressed in retinal ganglion cells in the fetal retina, human adult retina, and retinal organoids. Unexpectedly, after Fwk 20, Brn3 expression gradually decreased in the fetal retina. In the midstage of development, Islet1 was detected in bipolar and developing horizontal cells. As the photoreceptor developed, the Islet1-positive cone precursors gradually became Islet1-negative/S-opsin-positive cones. This study highlights the distinguishing characteristics of Islet1 dynamic expression in human fetal retina development and proposes more concerns which should be taken regarding Brn3 as a cell-identifying marker in mature primate retina.

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Background To develop an effective surgical procedure for cellular scaffold epiretinal implantation in rhesus, facilitating subsequent epiretinal stem cell transplantation. Methods Retinal progenitors were seeded onto a poly(lactic-co-glycolic) acid (PLGA) scaffold. First, the cellular scaffolds were delivered by 18G catheter or retinal forceps into rabbit epiretinal space (n = 50). Then, the cell survival rate was evaluated by Cell Counting Kit-8 (CCK-8). Second, three methods of scaffold fixation, including adhesion after gas-liquid exchange (n = 1), tamponade by hydrogel (n = 1), and fixation by retinal tacks (n = 4), were performed in rhesus monkeys. After one month, fundus photography and SD-OCT were performed to assess the outcomes, and histological examination was performed to evaluate proliferation. Results The cell survival rate was significantly higher in the catheter group. Follow-up examination showed that retinal tack fixation was the only method to maintain the scaffolds attached to host retina for at least 3 weeks, which is the minimal time required for cell integration. Histological staining demonstrated slight glial fibrillary acidic protein (GFAP) accumulation in the retinal tack insertion area. Conclusions The established surgical procedure offers a new insight into research of epiretinal cell replacement therapy in rhesus eyes. The successful delivery and long-term fixation provide a prerequisite for cell migration and integration.

Background Cerebral edema, inflammation, and subsequent neurological defecit, are the common consequences of intracerebral hemorrhage (ICH). Mesenchymal stem cells (MSCs) transplantation had been used as a neuroprotective therapy in nervous system diseases because of its anti-inflammatory effect. However, the survival, viability, and efficacy of MSCs are limited due to the severe inflammatory response after ICH. Therefore, ways to improve the survival and viability of MSCs will provide a hopeful therapeutic efficacy for ICH. Notably, the metal-quercetin complex via coordination chemistry has been verified positively and studied extensively for biomedical applications, including growth-promoting and imaging probes. Previous studies have shown that the iron-quercetin complex (IronQ) has excellent dual functions with a stimulating agent of cell growth and an imaging probe for magnetic resonance imaging (MRI). Therefore, we hypothesized that IronQ could improve the survival and viability of MSCs, displaying the anti-inflammation function in the treatment of ICH, while also label MSCs for their tracking by MRI. This study was designed to investigate the effects of the combined treatment of MSCs with IronQ on inflammation and elucidate their underlying mechanisms. Methods A collagenase I-induced ICH mice model was extablished, which were randomly divided into model group (Model), quercetin gavage group (Quercetin), MSCs transplantation group (MSCs), and MSCs transplantation combined with IronQ group (MSCs + IronQ). Then the neurological deficits score, brain water content (BWC), and the protein expression levels of IL-6, TNF-α, NeuN, MBP, and GFAP were investigated. We measured the protein expression levels of Mincle and its downstream targets. Furthermore, the lipopolysaccharide (LPS)-induced BV2 cells was used to investigate the neuroprotection of conditioned medium of MSCs co-cultured IronQ in vitro. Results We found that the combined treatment improves the inflammation-induced neurological function and BWC by inhibiting the Mincle/Syk signaling pathway in vivo. The conditioned medium of MSCs co-cultured with IronQ decreased inflammation, the protein expression levels of Mincle, and its downstream targets in LPS-induced BV2 cell line. Conclusions These data suggested that the combined treatment plays a synergistic role in ameliorating the consequences of ICH, including neurologic deficits, brain edema, and inflammatory response through the downregulation of the Mincle/syk signaling pathway.