Mohn Research Centre for Regenerative Medicine

Haukeland University Hospital, Helse Bergen, and the Faculty of Medicine at the University of Bergen established in 2021 the Mohn Research Centre for Regenerative Medicine (MRCRM). The centre is supported by the Trond Mohn Foundation over a 5-year period. The centre’s aim is to develop translational research and clinical trials within regenerative medicine in Bergen. The centre builds on the previous Bergen stem cell consortium (BSCC) and the ex vivo clean room facility in the Laboratory Building for the preparation of cells for use in clinical trials.

Regenerative medicine is the common denominator for various treatments where cell therapy is used to repair or replace – i.e. regenerate – tissues or cells that have been damaged by disease or accidents.

The field is developing rapidly, and the new solutions and methods are fundamentally innovative. Four research projects have received funds from Trond Mohn Foundation as part of the center´s research strategy. They cover topics ranging from psychosis research, wound treatment, the generation of new bone tissue and the treatment of cancer and method development. The projects have been evaluated by an international panel of experts.

The Trond Mohn Foundation has set aside a total of NOK 20 million to support 4 research projects (see below). In addition, the Foundation has also set aside NOK 5 million for a collaborative project between Bergen and Oslo in the core facility for genetically modified cell therapy in Oslo.

 

The center is led by Einar K. Kristoffersen, head of the Department of Immunology and Transfusion Medicine at HUS and professor at Clinical Institute 2, UiB. A board has been established for the center with representatives from both institutions.

The Trond Mohn Foundation supports the following research projects in the centre:

 

Establishment of protocols for the production of genetically modified cells for clinical use: New treatment for patients with acute leukemia (Collaboration between Oslo and Bergen)

PI: Einar Klæboe Kristoffersen, Helse Bergen

Patients with acute leukemia will be the first group of patients who, through the project, will be treated with their own T cells (a subgroup of white blood cells which together with two other subgroups, B cells and killer cells, make up the body’s most important immune system), which will be modified to express a new therapeutic T-cell receptor that can identify its own cancer cells and kill them. The study will be unique in an international context, and the first to use a new method for the treatment of malignant blood diseases that the applicants developed themselves. The project leaders say that the outstanding results achieved in the treatment of B-cell cancer with genetically modified T cells have triggered a huge international effort to develop new cell and gene therapy. At the same time, advances in cell biology have opened up new possibilities for creating new cells for the treatment of chronic diseases and defective tissues. The protocols, and the expertise developed through the project, will serve as the foundation for future protocols for gene therapy in Norway. The first ‘blueprint’ protocol will be implemented in a clinical trial that includes patients with acute leukemia, mentioned at the outset. Other protocols being developed in the project will utilize CRISPR/Cas9 for precise genetic correction of disease-causing mutations in mesenchymal stem cells (a type of stem cells that give rise to, for example, bone, cartilage, fat and blood vessels), and to modify T cells into CARs. The protocols will enable approval of the genetically modified cells for use in patients, initially in trial treatment studies, but with a clear goal of establishing cell therapy as a treatment option for Norwegian patients

Personalized medicine in the treatment of psychosis

PI: Erik Johnsen, Helse Bergen

The project will investigate why schizophrenia patients react differently to the same treatment (antipsychotic drugs). The aim is to find genetic or cellular ways to distinguish between two different types of schizophrenia in order to improve diagnosis and develop new forms of treatment tailored to the individual. A third of the patients have a type of schizophrenia that does not respond to the usual treatment of antipsychotic drugs, and it may take several years before this patient group receives relevant treatment. This can have a major negative impact on the forecast. Project leader Erik Johnsen elaborates: As the treatment-resistant type of schizophrenia is still an area of ​​significant medical challenges, identifying biological differences between the two subgroups of schizophrenia will accelerate the development of clinical aids to distinguish people with schizophrenia in the early phase of the disorder. The expert panel that evaluated the projects states: “The primary goals of this proposal are both exceptionally innovative and translatable.”

Mesenchymal stem cell transplantation in chronic wounds – development of precision medicine

PI of the work package “Eye Wounds”: Cecilie Bredrup, Health Bergen

PI of the work package “Burn Wounds”: Stian Kreken Almeland, Health Bergen

Project manager Cecilie Bredrup says that chronic and large acute wounds constitute a significant health problem. However, new forms of treatment involving advanced cell therapy  are revolutionizing our treatment of these conditions. Mesenchymal stem cells in particular (a type of stem cells that give rise to, for example, bone, cartilage, fat and blood vessels (MSC)) have many advantages: they are easy to harvest, they can be easily grown in vitro (outside the body) and they tolerate freezing. In addition, allogeneic stem cells (stem cells from another person) can be transplanted without the need for immunosuppression after transplantation. In this project, the researchers will use already approved and established protocols for manufacturing of mesenchymal stem cells harvested from the patient’s bone marrow, and investigate whether they are suitable for treating the patient’s own large/acute or chronic wounds on the skin (caused by burn damage) and the eye, Bredrup elaborates. Treatment effect will be assessed with sophisticated and innovative methods to develop a future biomarker program for cell therapy of wounds. In addition, we will do preclinical experiments to evaluate the effect and safety of using mesenchymal stem cells from another person with a long-term goal of using these in clinical trials. The evaluation panel writes in its report that “.. the potential impact of this proposal is quite impressive. Large numbers of patients could benefit from advances in the area.”

Clinical treatment of osteonecrosis with stem cells from bone (OsteoStem)

PI: Kamal Mustafa, UiB

Osteonecrosis is a bone disease caused by reduced blood supply to the bone tissue in one or more joints. Without adequate blood supply, the body will not be able to form new bone when old bone tissue dies. The condition is difficult to treat and causes significant discomfort and reduced quality of life for a large number of patients worldwide. A promising approach within regenerative medicine is cell therapy and controlled tissue regeneration. Mesenchymal stem cells (MSC) from bone marrow are multipotent stem cells from adults that can develop in different cell directions, renew themselves, and suppress the body’s immune response. Good results have been achieved in the treatment of necrosis (cell/tissue death) in the femoral head, and project leader Kamal Mustafa’s research group has recently shown that MSC is suitable for rebuilding jawbone in otherwise healthy patients. Mustafa says that the aim of the OsteoStem project is to evaluate the safety and effectiveness of using MSCs to treat bone defects in patients with osteonecrosis. The project will investigate the treatment effect with MSC in osteonecrosis patients, who need new bone tissue due to the disease, as has previously been carried out for healthy patients, who needed new bone tissue due to damage. MSC in the treatment of osteonecrosis will be an innovative and gentle treatment approach compared to the treatment options available today. The expert panel emphasizes the project’s innovative qualities: “..the primary goals of this proposal are both innovative and translatable”.

Scientific leadership at the center:

• Einar Klæboe Kristoffersen, HBE/UiB (Leader)
• Erik Johnsen, HBE/UiB
• Kamal Mustafa, UiB
• Cecilie Bredrup, HBE/UiB
• Stian Kreken Almeland, HBE/UiB
• Bjørn Tore Gjertsen, HBE/UiB
• Kimberley Joanne Hatfield, HBE
• Cecilie Gjerde, UiB
• Guro Kristin Melve, HBE
• Elise Aasebø, HBE – coordinator