Standardising the undefined: mesenchymal stromal cells in regenerative medicine

Mesenchymal stromal cells (MSCs) have immunomodulatory and anti-inflammatory effects, can be differentiated to multiple cell lineages and can induce pro-reparative changes in other cells. They are easy to obtain from multiple tissues. However, heterogeneity both in vivo and in cultured populations makes identification extremely challenging, and sub-populations within cultures frequently display widely differing functional characteristics. MSCs are the most intensely studied cell type in regenerative medicine, and are the subject of over 1500 clinical trials. Despite this, fewer than 20 MSC-based products are authorised for use worldwide. Literature attributes this minimal clinical success, in part, to a lack of standardisation which could reduce the impact of biological variation and improve consistency of clinical outcomes. However, there is no clear picture of the types of standards that could be beneficial, nor of the expectations or requirements of stakeholders involved in clinical translation of MSCs. My research evaluates the attributes of MSCs that could impact on their potential for standardisation and the challenges to standardisation they present, seeking to determine whether standardisation is a realistic goal for MSCs and what specific types of standards could facilitate clinical adoption and uptake of MSCs. Aspects of MSC biology that impact upon standardisation activities are identified. I have analysed consequences of poor characterisation on the development of MSC-based therapies. By interrogating the views of scientists working on translation of MSCs, I have identified types of standards that are likely to be of most value to them, analysing their opinions and concerns to produce recommendations for future standards generation activities. The work highlights a clear need for journal/editorial standards in the publication of MSC research, and identifies a potential framework for development of standard methods and other recommendations likely to be of value to academic researchers and translational scientists.