J Mol Neurosci. 2018 Apr 28. doi: 10.1007/s12031-018-1070-x. [Epub ahead of print]

Mesenchymal Stem Cells Form 3D Clusters Following Intraventricular Transplantation.

Jungwirth N^1,2, Salinas Tejedor L^2,3, Jin W^1,2, Gudi V^2,3, Skripuletz T³, Stein VM⁴, Tipold A^2,4, Hoffmann A⁵, Stangel M^2,3, Baumgärtner W^6,7, Hansmann F^1,2.

Abstract

Mesenchymal stem cells (MSCs) are regarded as an immune privileged cell type with numerous regeneration-promoting effects. The in vivo behavior of MSC and underlying mechanisms leading to their regenerative effects are largely unknown. The aims of this study were to comparatively investigate the in vivo behavior of canine (cMSC), human (hMSC), and murine MSC (mMSC) following intra-cerebroventricular transplantation. At 7 days post transplantation (dpt), clusters of cMSC, hMSC, and mMSC were detected within the ventricular system. At 49 dpt, cMSC-transplanted mice showed clusters mostly consisting of extracellular matrix lacking transplanted MSC. Similarly, hMSC-transplanted mice lacked MSC clusters at 49 dpt. Xenogeneic MSC transplantation was associated with a local T lymphocyte-dominated immune reaction at both time points. Interestingly, no associated inflammation was observed following syngeneic mMSC transplantation. In conclusion, transplanted MSC formed intraventricular cell clusters and exhibited a short life span in vivo. Xenogeneically in contrast to syngeneically transplanted MSC triggered a T cell-mediated graft rejection indicating that MSCs are not as immune privileged as previously assumed. However, MSC may mediate their effects by a "hit and run" mechanism and future studies will show whether syngeneically or xenogeneically transplanted MSCs exert better therapeutic effects in animals with CNS disease.