1.4. Future applications in tissue-engineering therapies

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)

1.4.1. Efficient differentiation and purification of the cell type of interest

1.4.2. Genetic stability and tumourigenic potential

1.4.3. Immune compatibility

Tissue engineering is a concept that evolved from organ transplantation and has existed since the mid 1980s – over a decade before the isolation of the first hESC lines. It aims to maintain or restore function to tissues whose failure is threatening illness. This can be done in three different ways: the support of preexisting tissues to prevent loss of function; the encouragement of damaged tissues to regain lost function; and the replacement of lost or damaged tissue. The main approaches have included treatment with bio-active molecules such as inhibitors and growth factors, the use of structural biomaterials as scaffolds and the introduction of new cells or tissues, as well as various combinations of these methods.

Many approaches to cell or tissue transplantation have met with significant levels of success. One of the best established of these procedures is the autologous transplantation of hematopoietic stem cells to restore blood cell production after chemotherapy-induced bone marrow ablation. Other cell therapies include the implantation of foetal dopaminergic neurons into patients suffering from Parkinson’s disease (Ali et al., 2013), the grafting of a retinal pigmented epithelium (RPE)-choroid patch to treat age-related macular degeneration (Buchholz et al., 2013) and transplantation of Islet cells or the whole pancreas to treat diabetes (Pavlakis and Khwaja, 2007). Each of these examples provides good proof of concept for cell-replacement therapy, but restricted levels of source tissue prevent many such therapies from being commonly applied in a clinical setting.

Human pluripotent stem cells, such as hESCs and hiPSCs, have the potential to solve this issue. Theoretically, they can differentiate into virtually any cell type in the human body, allowing a single source of cells to be applied to multiple different clinical uses. Furthermore, unlike many primary cell types, hPSCs can be easily maintained in culture and it is possible to scale up their cell numbers exponentially. This means that they have the potential to solve the problem of tissue supply faced by cell-replacement tissue engineering and even to provide previously unobtainable cell types for regenerative purposes.

So far, very few clinical trials that aim to utilize hPSC-derived tissues for replacement therapies have been announced. The differentiation potential and long-term in vitro culture of hPSCs introduces a level of complexity to the engineering process that makes an understanding of early human development, and subsequent control of cell phenotype, an essential key to success. Issues facing the implementation of hPSC-derived replacement therapies are: production and maintenance of high-quality and safe source hPSCs; development of efficient protocols for generating the cell type of interest; acquisition of pure differentiated cells of interest, without contamination of undifferentiated or other unwanted cell types; and circumvention of immune-compatibility issues, to prevent immune-rejection (Figure 1.8).


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