Bioengineered substrates for human pluripotent stem cell culture (360G-Wellcome-204401_Z_16_Z)
Human pluripotent stem cells (PSCs) have enormous potential to treat various degenerative diseases and the first UK clinical trial “The London Project to Cure Blindness” involving these cells is now underway. This trial is focussing on age-related macular degeneration (ARMD) and involves transplanting PSC-derived retinal pigment epithelial (RPE) cells into the eye. There is now much optimism that similar PSC-based therapies could be used to treat other diseases, such as Parkinson’s Disease (PD). However, a current impedance to the translation of PSC-based therapeutics for such diseases is that it is difficult and very costly to produce sufficient numbers of cells under the necessary GMP and xeno-free culture conditions. Treating ARMD is not so problematic because only 50 thousand PSC-derived RPE cells need to be transplanted into the eye. However, to treat a patient with PD, 10 million PSC-derived dopaminergic neurons would be needed. Therefore, there is a pressing need for improved culture conditions to facilitate the scale-up of PSCs for clinical use. To address this need, we have developed a molecularly engineered protein-based PSC culture substrate that can be easily and cheaply produced. The proteins that constitute the building-blocks of this engineered substrate are of human origin and are produced in high yield via recombinant overexpression in bacteria. Thus, there is high scale-up potential. Our current data show that this substrate can support the self-renewal of human PSCs. We now need to develop a more thorough data package before moving on to scale-up activities. Goals: (i) assess whether the substrate can support the self-renewal of several different PSC lines in xeno-free medium; (ii) assess whether PSCs maintain a normal phenotype and can be differentiated to specific lineages; (iii) investigate if PSCs maintain a normal karyotype; (iv) investigate if the substrate is immunogenic The potential healthcare impact of our PSC culture substrate is that it will enable the affordable scale-up of PSCs under GMP and xeno-free conditions so that therapeutic cell types such as PSC-derived dopaminergic neurons can be generated in sufficient quantities for clinical applications.
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Grant Details
Amount Awarded | 101221 |
Applicant Surname | Murray |
Approval Committee | Pathfinders Assessment Group |
Award Date | 2016-09-01T00:00:00+00:00 |
Financial Year | 2015/16 |
Grant Programme: Title | Pathfinder Award |
Internal ID | 204401/Z/16/Z |
Lead Applicant | Prof Patricia Murray |
Other Applicant(s) | Dr Neill Liptrott |
Partnership Value | 101221 |
Planned Dates: End Date | 2018-10-31T00:00:00+00:00 |
Planned Dates: Start Date | 2016-11-01T00:00:00+00:00 |
Recipient Org: Country | United Kingdom |
Region | North West |