Analysis of d-dimer as stem cell treatment marker and cytokines as prognostic marker in intravenous transplantation of umbilical cord-derived mesenchymal stem cells for acute stroke

Abstract

Stem cell clinical trials for stroke patients have been increasingly investigated, but their results have controversy. We recently performed the human umbilical cord-derived mesenchymal stem cells (Cordstem-ST) intravenous transplantation in acute cerebral infarction and found that Cordstem-ST had effects on functional improvement in stroke. In this study, we evaluated the possibility of therapeutic marker through the D-dimer and cytokine analysis in treatment of Cordstem-ST for stroke. In total 19 patients, we investigated the differences of D-dimer between placebo (4 patients) and stem cell groups (15 patients). And then, we analyzed differences of interval changes of various cytokines level between groups. Also, we investigated association between interval change of various cytokines and prognosis (good and poor) among stem cell group. D-dimer on following day after administration of Cordstem-ST was markedly increased in stem cell group than placebo group with significance on day 1. In interval change of D-dimer, there were significant differences on 1, 3, and 7 days. Although d-dimer was increased, but suspicious inflammatory symptoms and signs such as fever and leukocytosis was not accompanied. IL-1 alpha and IL-21 was markedly decreased in stem cell group than placebo group. Good prognosis group had higher level of BDNF, CCL2, CXCL10, PDGF-BB, and PLGF than poor prognosis group. It was suggested that D-dimer was a marker of stem cell treatment. And we found that Cordstem-ST increased cytokines related to anti-inflammation, neuronal regeneration and neovascularization.