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MRC DiMeN Doctoral Training Partnership: In vivo characterisation and optimisation of a novel engineered micro pancreas (EMP) for supporting clinical translation in diabetes treatment


MRC DiMeN Doctoral Training Partnership

, Dr William E Scott III , Dr Nikolai Kunicher Wednesday, January 27, 2021 Competition Funded PhD Project (Students Worldwide)
Leeds United Kingdom Biomedical Engineering Biotechnology Cell Biology Endocrinology Immunology Manufacturing Engineering Pathology

About the Project

Background: A major hindrance in the lives of diabetic patients remains the constant need to regulate blood glucose levels with the administration of insulin. With the inability to self-regulate blood-glucose, diabetics are at risk for many other ailments. Current islet transplantation techniques (Edmonton protocol) can restore normoglycemia, with limited effectiveness due to limited pancreatic islet supply from cadaver donors. Recently, a novel biologically engineered micro pancreas (EMP) using decellularised porcine lung tissue has been developed, which mimics the complex natural tissue micro-environment for supporting human islets viability and improve transplantation outcomes.

Objectives: To generate an immune-suppressed diabetic rat model for further testing and to optimise the novel EMP for supporting effective clinical diabetes treatment. 

Novelty: The EMP is using a novel decellularised micro-organ matrix (MOM) derived from porcine lung tissue. This project is focused on developing a pre-clinical animal model for the validation of this novel technology for promoting the development of an innovative regenerative therapy to restore insulin production in insulin-dependent patients. MOM provides an implantable 3D microenvironment enabling higher viability and long-term functioning of human islets, resulting in fewer donor cells needed per transplantation. When combined with human pancreatic islets, it generates functional EMPs that will be implanted subcutaneously, resulting in regulation blood glucose levels in diabetic patients. The previous data has established the scaffold's characteristics and demonstrated the safety and initial efficacy of the EMP in vitro (high feasibility).  

Timelines: 1) Induction and training (M1-6); 2) develop rat diabetic model, include industry lab-placement (M7-12); 3) compare different delivery path and their effect on the  EMP functionality,  include  Newcastle lab-placement (M13-24); 4)  compare the efficacy of different doses of the implants (M25-36); 5) thesis writing (M37-42). This project will be run in parallel with planned R&D and phase-1 clinical trials. Project success will provide evidence for supporting commercialisation and clinical translation. 

Experimental Approach: MOM will be provided by our industrial partner, and human islets provided by Newcastle University. Initially, a nude rat model will be used for developing a diabetic model, following its success, the site of implantation, dose and viability of the EMPs will be optimised. Selected doses of EMPs will be validated for the efficacy of insulin production in comparison with the control group with the administration of insulin. The EMPs will be stopped for histological analysis (e.g. viability, beta-cell, insulin content) at varying time points.  

This project offers the opportunity to develop quantitative skills such as islet viability and functionality as well as the efficiency of the EMP in an animal model (e.g. blood glucose and insulin level). Furthermore, interdisciplinary skills will be gained from an academic-clinical-industrial relationship enabling productive and positive collaborative ventures which will move us closer to a clinical endpoint. This project offers whole organism physiology via Home Office Model 1-4 training, surgical training and samples assessment. The student will be based in Leeds for in vivo testing but has the opportunities for lab placement in Newcastle (diabetes research, biomarkers) and the industry (EMP preparation at BetalinUK). 

iCASE Industrial Partner

This project is part of the Discovery Medicine North Doctoral Training Partnership (DiMeN DTP), a diverse community of PhD students across the North of England researching the major health problems facing the world today. Our partner institutions (Universities of Leeds, Liverpool, Newcastle and Sheffield) are internationally recognised as centres of research excellence and can offer you access to state-of the-art facilities to deliver high impact research.

We are very proud of our student-centred ethos and committed to supporting you throughout your PhD. As part of the DTP, we offer bespoke training in key skills sought after in early career researchers, as well as opportunities to broaden your career horizons in a range of non-academic sectors.

Being funded by the MRC means you can access additional funding for research placements, international training opportunities or internships in science policy, science communication and beyond. See how our current DiMeN students have benefited from this funding here: http://www.dimen.org.uk/overview/student-profiles/flexible-supplement-awards

Further information on the programme and how to apply can be found on our website:

https://bit.ly/3lQXR8A


Funding Notes

Funded by the MRC for 3.5yrs, including a minimum of 3 months working within the industry partner.

Funding will cover UK tuition fees and an enhanced stipend (around £17,785) only. We aim to support the most outstanding applicants from outside the UK. We are able to offer a limited number of bursaries that will enable full studentships to be awarded to international applicants. These full studentships will only be awarded to exceptional quality candidates, due to the competitive nature of this scheme. Please read additional guidance here: View Website
Studentships commence: 1st October 2021.
Good luck!

References

1. Mohanram Y, Zhang J, Tsiridis E, & Yang XB. (2020) Comparing bone tissue engineering efficacy of HDPSCs, HBMSCs on 3D biomimetic ABM-P-15 scaffolds in vitro and in vivo. Cytotechnology doi.org/10.1007/s10616-020-00414-7.
2. Saha S, Yang XB, Wijayathunga N, Harris S, Feichtinger GA, Davies RPW, Kirkham J. (2019) A biomimetic self-assembling peptide promotes bone regeneration in vivo: A rat cranial defect study. Bone 127:602-611.
3. Kelly, Amy C.; Smith, Kate E.; Purvis, William G. et al. (2019) Oxygen Perfusion (Persufflation) of Human Pancreata Enhances Insulin Secretion and Attenuates Islet Proinflammatory Signaling. Transplantation. 103(1):160-167.

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