Organ-on-chip: models of the female reproductive system
Lead Research Organisation:
University of Leeds
Department Name: Electronic and Electrical Engineering
Abstract
This project will be focused on the development of an "organ-on-a-chip" models for the recapitulation of the female reproductive tract.
The research goal of the project is to create Organ-on-a-chip models (OoC) that allow the co-culture of different cell types and the study of physiological functions of the female reproductive tract in vitro. These models will be used to assess change in metabolic activity of the specific cell types and the effect of exposure to chemical substances on some aspects of reproduction and fertility.
These innovative OoC models will allow: (i) the accurate study of the biochemical and functional activity of living tissues and (ii) the evaluation of the paracrine signalling that occurs in physiological and pathological conditions. Finally, human patient-derived cells will be used, thus considering the use of these models for the definition of personalized therapies for patients affected by diseases such as endometriosis and infertility.
The research goal of the project is to create Organ-on-a-chip models (OoC) that allow the co-culture of different cell types and the study of physiological functions of the female reproductive tract in vitro. These models will be used to assess change in metabolic activity of the specific cell types and the effect of exposure to chemical substances on some aspects of reproduction and fertility.
These innovative OoC models will allow: (i) the accurate study of the biochemical and functional activity of living tissues and (ii) the evaluation of the paracrine signalling that occurs in physiological and pathological conditions. Finally, human patient-derived cells will be used, thus considering the use of these models for the definition of personalized therapies for patients affected by diseases such as endometriosis and infertility.
People |
ORCID iD |
| Virginia Pensabene (Primary Supervisor) | |
| Vanessa Mancini (Student) |
Studentship Projects
| Project Reference | Relationship | Related To | Start | End | Student Name |
|---|---|---|---|---|---|
| EP/N509681/1 | 01/10/2016 | 30/09/2021 | |||
| 2123137 | Studentship | EP/N509681/1 | 01/12/2016 | 31/05/2020 | Vanessa Mancini |
| Description | we developed a microfluidic device that can be used to culture murine embryos until blastocyst stages. We tested gene expression profile of developed blastocysts and spent media samples collected from device to investigate metabolic profile of in vitro developed blastocysts. we also tested different culture media to optimize culture conditions. |
| Exploitation Route | Developing a product that can be used by IVF clinics for embyo culture |
| Sectors | Pharmaceuticals and Medical Biotechnology |
| Description | EPSRC TTL Sabbatical Project |
| Amount | £14,000 (GBP) |
| Organisation | Engineering and Physical Sciences Research Council (EPSRC) |
| Sector | Public |
| Country | United Kingdom |
| Start | 03/2019 |
| End | 09/2019 |
| Description | EPSRC TTL Sabbatical Project |
| Amount | £10,623 (GBP) |
| Organisation | Engineering and Physical Sciences Research Council (EPSRC) |
| Sector | Public |
| Country | United Kingdom |
| Start | 03/2019 |
| End | 09/2019 |
| Description | EPSRC TTTL Organ-on-a-Chip Technologies Network Small grant funding - Public engagement |
| Amount | £500 (GBP) |
| Organisation | Engineering and Physical Sciences Research Council (EPSRC) |
| Sector | Public |
| Country | United Kingdom |
| Start | 02/2020 |
| End | 04/2020 |
| Description | University of Leeds Early Career Researchers Internationalization Activity fund |
| Amount | £1,250 (GBP) |
| Organisation | University of Leeds |
| Sector | Academic/University |
| Country | United Kingdom |
| Start | 06/2019 |
| End | 09/2019 |
| Description | Alternative sustainable and biocompatible plastics |
| Organisation | Heriot-Watt University |
| Department | School of Engineering & Physical Sciences |
| Country | United Kingdom |
| Sector | Academic/University |
| PI Contribution | We are evaluating the use of 3D printed poly lactic acid (a sustainable, natural material) as alternative manufacturing material for microfluidic devices.The team of Prof. Kersaudy-Kerhoas is fabricating microfluidic devices and we are evaluating material toxicity with primary human cells (HUVEC) and murine embryos. |
| Collaborator Contribution | The team of Prof. Kersaudy-Kerhoas is providing different biocompatible materials (COC, PMMA, PLA, PDMS) to identify the most appropriate fr the fabrication of our microfluidic device for embryo culture. Her team is also providing ready to use devices that we are testing with primary cells, murine embryos and bovine embryos, in order to evaluate potential translation of the technique to human IVF. |
| Impact | This collaboration is multidisciplinary, since we are coupling material science, electronic engineering, microfabrication technology with biomedical engineering, reproductive biology and embryology. |
| Start Year | 2018 |
| Description | Early embryo implantation mechanism |
| Organisation | University of Leeds |
| Department | Faculty of Medicine and Health |
| Country | United Kingdom |
| Sector | Academic/University |
| PI Contribution | I am collaborating with Dr. Niamh Forde to study embryo implantation and to understand implantation failure. I am designing a new organ-on-a-chip model of the uterus. This uterus-on-a-chip will be made from a waste byproduct from the meat industry and has the potential to to replace mouse models . |
| Collaborator Contribution | Dr. Niamh Forde provides the protocols and expertise for the isolation and characterization of endometrial cells with different phenotypes (epithelial, stromal (fibroblast-like), endothelial cells) from bovine uteri. The tissues are routinely collected from a local abattoir, and procurement, handled and used following established protocols, approved by our University. Bovine embryos are generated from aspirating the oocytes from ovaries that would ordinarily be disregarded in the abattoir. As future task Dr. Forde is responsible for the analysis and evaluation of the bovine endometrial OoC response to steroid hormomes. |
| Impact | this activity is multidisciplinary since it involves biomedical and electrical engineering, microfabrication technologies and reproductive biology. |
| Start Year | 2018 |
| Description | Research collaboration with Dr. Nic Orsi on endometrium-embryo co-culture |
| Organisation | University of Leeds |
| Department | Faculty of Medicine and Health |
| Country | United Kingdom |
| Sector | Academic/University |
| PI Contribution | We started a collaboration with Dr. Nic Orsi at University of Leeds. Nic is an Academic Clinical Fellow in Histopathology at St James's Hospital (Leeds) After graduating in Animal Science (Reading), he pursued his combined interests in biochemistry and reproduction earning a PhD in early mammalian embryo development (York). Nic has extensive experience in the commercialisation of diagnostic/prognostic biomarkers and innovations aimed at improving pregnancy rates in both veterinary and clinical arenas., scientific advisor of Ostomara, a company founded in 2012 previously funded by NC3Rs. With this award and within the Marie Curie Fellowship that I hold, I am collecting human placentas from C-sections at ST James's Hospital with Nic Orsi's group to isolate cells to be used in the microfluidic device for studying the interaction between endometrial tissue and embryos at the time of implantation. The results of this collaboration will be useful for the application for additional research funding in the field of reproduction, fertility, preterm birth. |
| Collaborator Contribution | Nic Orsi has a tremendous knowledge in the field of fertility, embryology, human and mouse reproduction. In order to evaluate additional value of the microfluidic devices that we are developing in the final stage of the award, our PhD students are working together in terms of collecting tissue, isolating cells, staining placentas and isolating cells, measuring cytokines expressions in healthy tissues or in presence of inflammation or infection. |
| Impact | 1. We have presented one poster at the European Society of Human Reproduction and Embryology (ESHRE) Campus symposium "Methodological approaches for investigating endometrial function and endometriosis" in Edinburgh (September 18-19, 2017) titled "Microfluidic Model of the Human Endometrium". 2. We have submitted one abstract for oral presentation at the 34th Annual Meeting of the ESHRE that will be held in Barcelona (Spain) from 1 to 4 July 2018. The title of the abstract is "Investigating the correlation between infection and preterm birth (PTB) in a human organ-on-a-chip model of the human endometrium". These two works are obviously multidisciplinary since they involved engineering device of the microfluidic device, microfabrication of the device in the nanotechnology clean room, in vitro culture of primary cells and evaluation of cytokine expression. |
| Start Year | 2017 |