ATMP development for urethra reconstruction with de- and re-cellularization technique
Lead: Västragötalands Region (Sahlgrenska Univ Hosp)
Involved partners: Gothenburg University/Sahlgrenska Univ Hosp, RISE, Verigraft AB
Urethral stricture is a narrowing of the urethra, a common disease in men. The condition has a prevalence of 1% and with gender reassignment surgery rapidly growing, there is an additional demand for the type of ATMP being developed in this project. Following urethra stricture, urination is inhibited resulting in immense suffering and a significantly reduced quality of life. The surgery of such diseases is restricted with grafts of skin or buccal mucosa. We are developing personalised urethras through de-cellularisation and re-cellularisation of porcine urethras. Ethical approval for the animal study has already been achieved. The team will also evaluate the possibility to produce an 3D printed tubular structure, which will be used as a scaffold for the cells, in another upcoming animal study.
- develop a new personalized urethra for patients with a great medical need e.g. with urethral stricture, hypospadias or gender dysphoria.
- produce a functional Advanced Medicinal Therapeutic Product (ATMP) urethra for adults by utilizing a decellularized donor or 3D printed urethra scaffold, reconditioned with the patient’s own cells and other material.
- perform preclinical studies in a large animal model required to bring the concept to a first human
Examples of tasks and actions:
- Collecting cadaver urethras of male sheep (ram)
- Biopsy of the animal mouth (buccal mucosa) for cell culture of epithelial cells and smooth muscle cells
- De- and recellularization of the urethras
- Implantation of the recellularized urethras into the animals
- Follow up for 6-12 months with X-ray injection of contrast in the urethra, histology (biopsy of the urethra) and functional control of micturition
Interview with project leader
Hi Teresa Olsen Ekerhult!
What is the need your project addresses?
The project will address a huge medical need for patients in need of a new urethra. Expected long-term effects are that patients will not need to be reoperated in the current degree with skin grafts and buccal mucosal grafts, as the donated and personalized urethra will most likely be able to replace dysfunctional tissue. At present, many patients have catheters through a hole in the abdomen into the bladder and are on sick leave for several months to years. With the current treatment method, open urethroplasty, patients are operated 2-3 times to avoid relapse. This ATMP project has a great chance of success, which would mean that we proceed with a clinical human study after the preclinical, with the same technology, to restore patients’ micturition, with less sick leave, reduced risk of kidney damage, earlier return to work and above all reduced suffering as a result.
Any novel product in this area must be personalized in order to not be rejected by the patient´s immune system. The delivery of a tissue-engineered individualized urethra with properties similar to a native organ, will alleviate suffering and loss of quality-of-life and will lower the burden to our societies.
What is your approach to meet the need?
The challenge is to create a hollow tissue with the right cell composition and the establishment of vascular growth as well as the correct cell-types in the correct organization for adequate function. For this we need good planning and communication when working together as a group. We all have our specialities in the project group, that will benefit the progression of the study. We have to be able to adapt and to be innovative to follow our vision to develop a functional, personalized ATMP urethra.
How will this improve Sweden’s capabilities within ATMPs?
The solid pre-clinical data we aim of developing in this project will support the entrance of personalized urethras in clinical studies, and will ultimately bring significant value to patients, the society and to Sweden. Also, validating an ATMP product in solid short- and long-term in vivo studies like this will make a good trademark for this whole, relatively new, field and make a good imprint for Sweden as a leading country. It would also strengthen Sweden’s role as an international center for the reconstruction of the urinary tract, which in turn strengthens the life science/business link in this field.
For more information on this Project please Contact Teresa Olsen Ekerhult