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Ex Vivo Expansion of Hematopoietic Stem Cells in Conditioned Medium - Aarhus University Hospital

Ex Vivo Expansion of Hematopoietic Stem Cells in Conditioned Medium

Immunodeficient children are currently treated with allogenic hematopoietic stem cell (HSC) transplants. Initially, it can be extremely difficult to identify a suitable healthy stem cell donor. Once a donor is found, these transplants introduce severe and potentially life-threatening complications known as ‘Graft-versus-Host disease’, which persist throughout the patient’s lifetime.

The Inspiration Behind the Innovation 

Autotransplantation using a patient’s own gene-edited HSC could circumvent the need for a stem cell donor and mitigate the severe side effects associated with allogenic transplantation. The introduction of CRISPR/Cas9-based gene editing has made precise gene correction possible. However, its clinical introduction is dependent on larger numbers of HSC than what is presently available post-correction, as well as HSC with retained stemness to enable lifelong function after autotransplantation.

The Innovation 

After attempting co-culture with mesenchymal stem cells (MSC) to mimic the interaction of HSC and MSC in bone marrow, the team has demonstrated that heat-activated MSC (HI-MSC) without metabolic activity and evenly conditioned medium from HI-MSC have the ability to support the expansion of HSC with increased retention of hematopoietic stemness as compared to conventional culture conditions. This increase in stemness is key to a successful introduction of CRISPR/Cas9-based gene editing of HSC, and may also facilitate autologous HSC transplantation in patients with inferior mobilisation of stem cells after G-CSF treatment.

This solution uses inactivated mesenchymal stem cells and derivatives for GMP-compliant expansion of hematopoietic stem cells. This will be combined with gene-editing of HSC, resulting in a therapeutic relevant amount of edited cells with retained stemness, which fills an unmet medical need for a group of patients who are dependent on hematopoietic stem cell transplantation.

The Team 

Bjarne Møller: Head Consultant, Assoc. Professor; Department of Clinical Immunology, AUH

Anne Louise S. Revenfeld: Clinical Specialist; Department of Clinical Immunology, AUH