Human iPS cell derived RPE strips for secure delivery of graft cells at a target place with minimal surgical invasion

Abstract

Several clinical studies have been conducted into the practicality and safety of regenerative therapy using hESC/iPSC-retinal pigment epithelium (RPE) as a treatment for the diseases including age-related macular degeneration. These studies used either suspensions of RPE cells or an RPE cell sheet. The cells can be injected using a minimally invasive procedure but the delivery of an intended number of cells at an exact target location is difficult; cell sheets take a longer time to prepare, and the surgical procedure is invasive but can be placed at the target area. In the research reported here, we combined the advantages of the two approaches by producing a quickly formed hiPSC-RPE strip in as short as 2 days. The strip readily expanded into a monolayer sheet on the plate, and after transplantation in nude rats, it showed a potency to partly expand with the correct apical/basal polarity in vivo, although limited in expansion area in the presence of healthy host RPE. The strip could be injected into a target area in animal eyes using a 24G canula tip.

Multicellular dynamics on structured surfaces: Stress concentration is a key to controlling complex microtissue morphology on engineered scaffolds

“…Quantitative knowledge is particularly helpful when designing scaffolds that actively utilise cellular detachment to engineer microtissues in three dimensions. For example, collective cellular detachment can be, if controlled, employed to create microtissues in unique 3D morphologies, such as strings [69] and bridges between piers [70]. Our modelling framework is in principle applicable to simulate cellular detachment from a scaffold in confined 3D environments, e.g., tubular structures (Fig.…”

“…Quantitative knowledge is particularly helpful when designing scaffolds that actively utilise cellular detachment to engineer microtissues in three dimensions. For example, collective microtissue detachment can be, if controlled, employed to create microtissues in unique 3D morphologies, such as strings [58] and bridges between piers [59]. The mechanical understanding shown in this study would give deep insights into various aspects of scaffold design in tissue engineering, including scaffold geometry, surface treatments and growth factors.…”

The Prospects for Retinal Organoids in Treatment of Retinal Diseases

“…RPE plays critical roles in vision by performing vital functions such as: (1) transporting nutrients, ions, and water to the PRs; (2) supplementing 11-cis-retinal in the visual cycle by isomerization of all-trans-retinal; (3) protecting against photooxidation and light absorption; (4) removing shed PR outer segment membranes with phagocytosis; and (5) secreting essential extracellular molecules (eg, laminin, collagen, and HA) to maintain retinal integrity, functionality, and PR viability. 106,107 Several studies used hESC/iPSC-derived RPE sheets (or "patches") for retinal degenerative therapy in animal models [108][109][110][111] and clinical trials [112][113][114][115] (reviews 116,117 ). These studies reported maintenance or improvement of visual function and delated RD.…”

iPSC Therapy for Myocardial Infarction in Large Animal Models: Land of Hope and Dreams

“…Direct iPSC delivery through transplantation or injection has become the most studied approach in regenerative medicine [ 101 , 102 , 103 , 104 , 105 , 106 , 107 ]. However, iPSC translational efforts have been dampened by concerns regarding the teratogenic potential of undifferentiated cells, as well as the lack of timely stimuli to carefully guide the in situ differentiation of these cells [ 108 ].…”