PRINTING CELLS

An adult retinal ganglion cell being inkjet printed. Courtesy of Wen-Kai Hsiao, University of Cambridge

A team of researchers at the University of Cambridge, UK has succeeded in using inkjet printing technology to print viable cells of the adult rat central nervous system (CNS), retinal ganglion cells (RGC) and glia.

The research has important implications for the survival and growth of these cells in culture and represents an important step in the development of tissue grafts for regenerative medicine, according to Keith Martin FRCOphth, Professor of Ophthalmology at the University of Cambridge, who led the study.

“This study is proof of the principle that retinal neurons and glia can be inkjet printed and opens up the possibility of using this technology to organise cells in very precise arrangements relative to each other,” he told EuroTimes.

“In the short-term, this may allow us to do new types of experiments on how retinal cells interact, but in the longer-term we are keen to develop ways to start to engineer retinal tissue for retinal repair,” he added.

Prof Martin’s team showed that a piezoelectric print head does not significantly affect the viability of printed adult RGC and glial cells. The research paper, published in the journal Biofabrication (Lorber B et al, 2014 Biofabrication 6 015001; doi:10.1088/1758-5082/6/1/015001), reported that even though the cells are subjected to very high shear rates and acceleration during jetting, no significant distortion of the cell structures was observed either immediately before or after cell ejection.

“The observations suggest that either the cell membranes possess sufficient strength and elasticity to resist a brief period of high stress, or the geometry of the print head nozzle used results in rather little shear or deformation of the cells during jetting,” the authors reported.

The fact that RGC and retinal glial cells do not appear to be affected by the printing process and retain their phenotype in culture opens up the possibility for studying interactions of these cells when printed in precise locations and patterns, explained Prof Martin. This could enable the creation of cell arrays mirroring the in vivo situation, which would allow screening the effect of novel compounds on cell-cell interactions before application in vivo.

NEW AVENUES

The research also opens new avenues for creating printed tissue grafts for use after CNS injury in vivo. While this has only been demonstrated thus far with a few cell types using thermal inkjet printers, Prof Martin and co-workers suggest that RGC and glia may potentially be organised in the future using piezoelectric inkjet printers.

“We have previously used crosslinked fibrin gels to deliver cells to the injured spinal cord in animal models. Given the growth promoting effects of a substrate of printed glial cells, as observed in the present study, it will be interesting to investigate in future studies if a printed fibrin-glial construct might promote functional recovery following optic nerve or spinal cord injury in vivo,” the authors said.

From an ophthalmology perspective, it will be important to extend the research to other cells of the retina and investigate if light-sensitive photoreceptors can be successfully printed using inkjet technology, said Prof Martin.

“If this can be proven, printing of functional retinal cells to help cure some forms of blindness could be within reach. I think RPE cells and possibly photoreceptors are good candidates, although we have yet to complete these experiments,” he added.

Prof Martin notes, however, that many hurdles still need to be overcome to translate the findings of the research to the living human retina.

“We are a long way from repairing the human neural retina. It remains to be seen if these techniques could be used inside a living eye or whether a better approach will be to engineer tissues outside the eye and transplant later. However, we are a very long way from being able to recreate the complexity of a living human retina which is of course characterised by hugely complex interactions between many different cell types,” he concluded.

Keith Martin: krgm2@cam.ac.uk