Cd34⁺progenitor cells likely are involved in the good functional recovery after intracerebral hemorrhage in humans

Abstract

Bone marrow-derived stem/progenitor cells (CD34(+) progenitor cells) were demonstrated to play an important role in the regeneration of damaged brain tissue. Our aim was to study the influence of CD34(+) progenitor cells in the outcome of intracerebral hemorrhage (ICH). Thirty-two patients with primary ICH (64.0% male, mean age 67.1 ± 10.8 years) were prospectively included in the study within 12 hr of symptom onset. The main outcome variable was good functional outcome at 3 months (modified Rankin scale ≤ 2). Circulating CD34(+) progenitor cell levels were measured by flow cytometry at admission and at 7 ± 1 days, and serum levels of growth factors (determined by ELISA) were measured at admission and at 24 and 72 hr. Circulating levels of CD34(+) progenitor cells at day 7 were independently associated with good functional outcome at 3 months (OR 1.17, CI95% 1.06-1.39, P = 0.012). On the other hand, CD34(+) progenitor cells at day 7 were negatively correlated with residual cavity volume at 3 months (r = -0.607, P = 0.001). Serum levels of vascular endothelial growth factor (r = 0.386), angiopoietin 1 (r = 0.518), brain-derived neurotrophic factor (r = 0.484), and stromal cell-derived factor-1α (r = 0.837) but not granulocyte-colony stimulating factor (r = -0.038) at 72 hr showed a strong correlation with CD34(+) progenitor cell levels at day 7. These findings suggest that CD34(+) progenitor cells may participate in the functional recovery of ICH patients.

Potential Role of Blood Biomarkers in the Management of Nontraumatic Intracerebral Hemorrhage

“…In blood sampled from 32 ICH patients within 12 h from symptom onset and on day 7, CD34 levels at day 7 but not day 1 positively correlated with good functional outcome (OR = 1.17) and negatively with residual cavity volume at 3 months (r = -0.607) [68]. A strong correlation was also found between CD34 levels and GFs at day 7.…”

Neovascularization and functional recovery after intracerebral hemorrhage is conditioned by the Tp53 Arg72Pro single-nucleotide polymorphism

“…9 Neovascularization after cerebral ischemia is promoted by circulating CD34 + progenitor cells 11, 13, 14, 25 and, although the mechanism is unknown, it correlates with functional outcome in ischemic stroke 15, 16, 17 and ICH 18 patients. We first corroborated this correlation in our ICH cohort (Figure 2a).…”

“…Number of human CD34 + progenitor cells was expressed as absolute cell counts obtained after the measurement of 2.5 × 10 5 events in the lymphocyte gate (FACS Diva software; BD Biosciences, Bergen, NJ, USA). 18 In some experiments, following CD34-FITC staining, cells were stained with annexin V-allophycocyanin (APC) and 7-aminoactinomycin D (7-AAD) in binding buffer (100 mM HEPES, 140 mM NaCl and 2.5 mM CaCl 2 ). CD34 + progenitor cells (identified by FITC fluorescence) were analyzed, and the annexin V-APC-stained cells that were 7-AAD-negative were considered to be apoptotic.…”

“…These progenitor cells are mobilized from the bone marrow after vascular injury and home to the site of neovascularization, contributing to regeneration by either direct incorporation into newly forming vascular structures or indirectly via the secretion of proangiogenic growth factors, thereby enhancing the overall vascular recovery of ischemic brain. 11, 12, 13, 14 Furthermore, emerging evidences confer to circulating EPC levels a prognostic value in the prediction of functional outcome in ischemic stroke 15, 16, 17 and ICH 18 patients.…”

Stem cell therapies in age-related neurodegenerative diseases and stroke

“…HSC transplantation has been demonstrated to eliminate the dysfunctional immune system, and reconstruct a new immune system that is more compatible with the nervous system, together with significant and sustained inhibition of inflammation (Blanco et al, 2005). HSCs can migrate to the damaged lesion site and rebuild viable endothelia, enhance neurogenesis/angiogenesis, modulate immune responses, as well as suppress oxidative stress and inflammatory activity (Baker et al, 2007; Shin et al, 2011; Sobrino et al, 2011). The short-term side effects of HSC transplantation include infections and engraftment syndrome, whereas the long-term complications include secondary malignancies, endocrine disorders, and autoimmune diseases (Blanco et al, 2005; Epstein et al, 2009; Orio et al, 2014).…”