ReviewCell therapy for basement membrane-linked diseases

- Basement membrane-linked diseases are a versatile group of disorders that affect every major organ system.
- For basement membrane-linked diseases curative effects may be achieved with incomplete and transient engraftment of cells.
- Disease-modifying mechanisms may also be targeted with cell-based therapies.
- Before wider clinical implementation can be considered, questions related to efficacy and mode of action need answers.
- At present localized therapies have the highest therapeutic potential.

For most disorders caused by mutations in genes encoding basement membrane (BM) proteins, there are at present only limited treatment options available. Genetic BM-linked disorders can be viewed as especially suited for treatment with cell-based therapy approaches because the proteins that need to be restored are located in the extracellular space. In consequence, complete and permanent engraftment of cells does not necessarily have to occur to achieve substantial causal therapeutic effects. For these disorders cells can be used as transient vehicles for protein replacement. In addition, it is becoming evident that BM-linked genetic disorders are modified by secondary diseases mechanisms. Cell-based therapies have also the ability to target such disease modifying mechanisms. Thus, cell therapies can simultaneously provide causal treatment and symptomatic relief, and accordingly hold great potential for treatment of BM-linked disorders. However, this potential has for most applications and diseases so far not been realized. Here, we will present the state of cell therapies for BM-linked diseases. We will discuss use of both pluripotent and differentiated cells, the limitation of the approaches, their challenges, and the way forward to potential wider implementation of cell therapies in the clinics.