Purpose
Several reports have highlighted the low immunogenic profile of MSCs. Therefore, we decided to test
in vivo
the humoral response to allogeneic MSCs transplantation and the effect of transient immunosuppression in a porcine model.
Methods/Material
MHC-controlled mini-swine SLA
cd
and SLA
dd
were used as donor and recipients, respectively. Two sites of transplantation were selected: subcutaneous and intracardiac. In our control group (n = 5), animals received no immunosuppression. In the study group (n = 11), nearly 1 x 10
6
allogeneic MSC/kg were injected. FK-506 was given from day 0 –12 and adjusted to therapeutic blood levels. Sera were serially collected up to one year after transplantation. The presence of specific anti-donor IgM and IgG was tested by flow cytometry and by a complement-mediated cytotoxicity assay.
Results
In the control group, all animals developed humoral responses in both IgM/G classes that persisted up to ten weeks. When transplanted subcutaneously, a single injection failed to elicit a complement-mediated cytotoxic response but subsequent re-challenge did. In the study group, only 2/11 FK-treated animals developed a transient humoral response, both in IgM and IgG, whereas all others failed to develop donor-specific antibodies. However, none of the sera tested from those 11 animals could elicit a complement-mediated cytotoxic response.
Conclusion
Allogeneic MSCs injected subcutaneously or intra-cardially can elicit prolonged humoral responses despite their putative low immunogenic profile. As already shown for experimental allogeneic organ transplantation, a transient immunosuppressive regimen can overcome the initial B cell response. Our result suggests that
in vitro
and
in vivo
characteristics of MSCs might differ and emphasizes the importance of pursuing research on allogeneic stem cell transplantation.
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