Chemokine Assay Matrix Defines the Potency of Human Bone Marrow Mesenchymal Stromal Cells

Potency analysis of mesenchymal stromal cells (MSCs) is required for their use in advanced clinical trials. Assay matrix strategy evaluating more than a single property of MSCs is an emerging strategy in potency analysis. Here we developed an assay matrix approach focusing on the secretory chemokine responses of MSCs using multiplex analytical method. MSCs' innate fitness in secreting matrix of chemokines is correlated with their metabolic fitness in differential degrees. In addition, innately secreting chemokines are correlated among themselves in a unique pattern. MSC's matrix chemokine responses to exogenous stimulation of IFN gamma and/or TNF alpha are distinct. However, the combination of IFN gamma and TNF alpha is superior than individual stimulations in eliciting robust and broad matrix chemokine responses of MSCs. Correlation matrix analysis has identified that chemokine responses to IFN gamma and/or TNF alpha display unique correlative secretion patterns. MSC and peripheral blood mononuclear cells coculture analysis has identified the correlation matrix responses of chemokines that predicted immune suppression. In addition, MSC-mediated blocking of T-cell proliferation predominantly correlates with chemokines in an inverse manner. Knockdown of chemokines has demonstrated that MSC-sourced inherent chemokines do not actively play a role in T-cell suppression and thus are the bystander predictors of T-cell suppression.The present analysis of MSC's matrix chemokine responses can be deployed in the advanced potency analysis of MSCs.

Automated summary

This study examined the secretory chemokine responses of mesenchymal stromal cells (MSCs) and developed a multiplex analytical method to evaluate their potency. The researchers found that MSCs' innate ability to secrete chemokines is correlated with their metabolic fitness, and the innate secretion of chemokines has a unique correlation pattern. They also found that the combination of IFN gamma and TNF alpha stimulation produces more robust and broad matrix chemokine responses in MSCs compared to individual stimulations. Additionally, the study identified chemokines that can predict immune suppression in MSC and peripheral blood mononuclear cell coculture analysis.