Table 1 Key unanswered or incompletely answered questions about mesenchymal stem cell effects on T-cell effector functions
From: Mesenchymal stem cell effects on T-cell effector pathways
1 | Is there a true hierarchy of suppressive potency for MSC effects on the three major T helper cell effector pathways (for example, Th1 cells > Th17 cells > Th2 cells)? |
2 | Are individual T-cell effector phenotypes susceptible to different MSC mechanisms of suppression, or does suppressive mechanism vary by MSC culture condition or by disease pathogenesis (or by both)? |
3 | How important is cell-cell contact for the in vivo direct and indirect suppression by MSCs of harmful T-cell effector functions? |
4 | Is the apparent shift from Th1/Th17 to Th2/Treg responses following MSC therapy in some diseases due to true induction and expansion of anti-inflammatory T-cell effector phenotypes or to their preferential survival? |
5 | What are the relative effects of MSCs on memory and pre-activated T-cell effectors compared with naïve T cells undergoing primary activation? |
6 | Do immunosuppressive potency and mechanism of action vary among the individual cells within heterogenous MSC cultures and can they be enhanced by MSC cloning or modification? |
7 | To what extent and under what circumstances are MSCs capable of promoting harmful T-cell effector functions? |
8 | How long-lasting is MSC modulation of antigen-specific T-cell effectors following single or multiple in vivo administration? |
9 | How can MSC in vivo immune suppressive potency, mechanism of action, and site of migration be better predicted for a given culture preparation prior to therapeutic administration? |
10 | Does the in vivo immunogenicity of allogeneic MSCs limit their long-term therapeutic benefit in autoimmune disease and allotransplantation? |
11 | What are the combined in vivo effects of MSC and other anti-T-cell therapies? |