WSO - April 2024 - 463
Mizuno et al.
463
Figure 1. Study flowchart.
the lowest tertile group. The numbers of patients with good
functional outcomes at 3 months and 1 year were 97 (54.8%)
and 84 (47.2%) in Tertile 1, 118 (69.0%) and 101 (59.1%)
in Tertile 2, and 137 (76%) and 126 (73.1%) in Tertile 3,
respectively. As shown in Table 3, the multivariate analysis
demonstrated that increased circulating CD34+ cell levels
were independently associated with good functional outcomes
at 3 months and 1 year. The optimal cut-off values
were 0.65/µL (sensitivity, 60%; specificity, 59.8%; AUC,
0.627) and 0.92/µL (sensitivity, 76.7%; specificity, 44.7%;
AUC, 0.637) for good 3-month and 1-year outcomes,
respectively.
Discussion
In this observational study including patients with stroke
within 1 week of symptom onset, the number of circulating
CD34+ cells did not predict the occurrence of MACE at
1 year. However, increased CD34+ cell levels were independently
associated with good functional prognoses at
3 months and 1 year. The optimal cut-off value of CD34+
cell counts to predict good functional outcomes at 1 year
was 0.92/µL, which showed moderate predictive strength.
CD34+ cells are markers of hematopoietic and nonhematopoietic
progenitor cells, such as EPCs and embryonic
fibroblasts.1 Under ischemic conditions, EPCs, producing
multiple cytokines and growth factors (e.g. stromal cellderived
factor-1 and vascular endothelial growth factor)
involved in neovascularization, are mobilized from the
bone marrow into the peripheral blood and migrate to vessels
of the injured tissues. EPCs contribute to form new
vessels and repair endothelial injury by proliferating and
differentiating into endothelial cells.3,10 EPCs, in addition
to neovascularization, induce neurogenesis via various
cytokines and growth factors in the cerebral infarct areas.11
In an in vivo study, intravenous CD34+ cell infusion after
stroke promoted neurogenesis via neovascularization in
mice.12 Previous clinical studies have shown that the number
of circulating CD34+ cells or EPCs was associated
with neurological functions in patients with ischemic
stroke.13-16 Camps-Renom et al.,13 Dunac et al.,14 MartíFàbregas
et al.,15 and Yip et al.16 reported the association
International Journal of Stroke, 19(4)
WSO - April 2024
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