Glaucoma is one of the leading causes of blindness, and there is an ongoing need for new therapies. Recent studies indicate that cell transplantation using Müller glia may be beneficial, but there is a need for novel sources of cells to provide therapeutic benefit. In this study, we have isolated Müller glia from retinal organoids formed by human induced pluripotent stem cells (hiPSCs) in vitro and have shown their ability to partially restore visual function in rats depleted of retinal ganglion cells by NMDA. Based on the present results, we suggest that Müller glia derived from retinal organoids formed by hiPSC may provide an attractive source of cells for human retinal therapies, to prevent and treat vision loss caused by retinal degenerative conditions. Stem Cells Translational Medicine 2019;8:775&784

Artificial tissues constructed from therapeutic cells offer a promising approach for improving the treatment of severe peripheral nerve injuries. In this study the effectiveness of using CTX0E03, a conditionally immortalised human neural stem cell line, as a source of allogeneic cells for constructing living artificial nerve repair tissue was tested. CTX0E03 cells were differentiated then combined with collagen to form engineered neural tissue (EngNT-CTX), stable aligned sheets of cellular hydrogel. EngNT-CTX sheets were delivered within collagen tubes to repair a 12 mm sciatic nerve injury model in athymic nude rats. Autologous nerve grafts (autografts) and empty tubes were used for comparison. After 8 weeks functional repair was assessed using electrophysiology. Further, detailed histological and electron microscopic analysis of the repaired nerves was performed. Results indicated that EngNT-CTX supported growth of neurites and vasculature through the injury site and facilitated reinnervation of the target muscle. These findings indicate for the first time that a clinically validated allogeneic neural stem cell line can be used to construct EngNT. This provides a potential ‘off the shelf’ tissue engineering solution for the treatment of nerve injury, overcoming the limitations associated with nerve autografts or the reliance on autologous cells for populating repair constructs.

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Injuries to the peripheral nervous system affect 1 in 1,000 individuals each year. The implication of sustaining such an injury is considerable with loss of sensory and/or motor function. The economic implications too are extensive running into millions of pounds (or dollars) annually for provision and support. The natural regrowth of peripheral nerves is possible for small gap injuries (of approximately 1-2 mm). However, patients with larger gap injuries require surgical intervention. The "gold standard" for repairing gap injuries is autografting; however, there are problems associated with this approach, and so, the use of nerve guidance conduits (NGC) is a realistic alternative. We outline in this chapter the development of an NGC that incorporates aligned poly-L-lactide fibres for supporting the growth of organised Schwann cells within a three-dimensional scaffold in vitro. A closed loop bioreactor for growing cells within NGC scaffolds is described together with a method of plasma deposition for modifying the microfibre surface chemistry (which improves the ability of Schwann cells to attach) and confocal microscopy for measuring cell viability and alignment within 3D constructs.