Principles of stem cell biology and cancer: future applications and therapeutics. Edited by T. Regad, T. J. Sayers and R. C. Rees. John Wiley & Sons (2015)
One of the most promising applications to date for stem cell-based tissue engineering is the treatment of the dry form of age-related macular degeneration (AMD) with hPSC-derived RPE. This is the first approach using hPSCs to move to clinical trials, partly because of the ease with which differentiation into RPE cells was first achieved. Human PSCs will spontaneously develop into RPE cells at low efficiencies and can be easily identified via pigmentation. Recent advances in differentiation protocols have increased efficiencies to ~60%, allowing purification of enough cells for transplantation into patients, through either the injection of a single cell suspension or insertion of a ‘patch’ of cells grown in a monolayer on a scaffold (Buchholz et al., 2013)* . These first clinical trials may successfully cure AMD and push hPSCs into a clinical era. However, they might also uncover unwanted side effects, such as those described with the first attempts to cure severe combined immunodeficiency (SCID-X1) by using gene therapy to genetically modify cells (Hacein-Bey-Abina et al., 2003). An early clinical trial conducted by the Geron Corporation attempted to use hESC derivatives to treat spinal cord injury, but it ended prematurely, partly because of the unanticipated cost of the project. This is an example of the unforeseen hurdles that can still slow advancement to treatments.
The use of hPSCs for tissue engineering could circumvent issues of tissue supply, regress symptoms of neurodegenerative diseases rather than just alleviate them, and provide replacement cells that were previously unobtainable. The approaches described in this chapter represent only those that are closest to clinical use. In the future, it may be possible to use gene therapy to cure genetic defects in the iPSCs of patients before re-implanting them as an autologous cell-replacement therapy, and even to use additive manufacturing to create whole organs from hPSC derivatives (Orlando et al., 2013). Currently, the costs of these therapies are prohibitive, but, although the need for extensive preclinical analysis of cells will always be present, optimization of these procedures alongside differentiation, transplantation and reprogramming will eventually bring costs down.
As our understanding of human embryology expands and we learn to better recapitulate it in vitro, we can expect to see the number of applications for hPSCs in tissue engineering rise exponentially.
* Since the time of writing trials have shown improvements in the eyesight of patients taking part in trials for this treatment of AMD (Schwartz et al., 2014).
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