Timing of Cord Blood Treatment after Experimental Stroke Determines Therapeutic Efficacy

Abstract

Embolic stroke is thought to cause irreparable damage in the brain immediately adjacent to the region of reduced blood perfusion. Therefore, much of the current research focuses on treatments such as anti-inflammatory, neuroprotective, and cell replacement strategies to minimize behavioral and physiological consequences. In the present study, intravenous delivery of human umbilical cord blood cells (HUCBC) 48 h after a middle cerebral artery occlusion (MCAo) in a rat resulted in both behavioral and physiological recovery. Nissl and TUNEL staining demonstrated that many of the neurons in the core were rescued, indicating that while both necrotic and apoptotic cell death occur in ischemia, it is clear that apoptosis plays a larger role than first anticipated. Further, immunohistochemical and histochemical analysis showed a diminished and/ or lack of granulocyte and monocyte infiltration and astrocytic and microglial activation in the parenchyma in animals treated with HUCBC 48 h poststroke. Successful treatment at this time point should offer encouragement to clinicians that a therapy with a broader window of efficacy may soon be available to treat stroke.

Neurorestorative treatment of stroke: Cell and pharmacological approaches

“…39,40 Thus, MSC treatment is poised for clinical trials in stroke. Preclinical data point to other cell therapies that appear highly efficacious in reducing neurological deficits after stroke, 15,22,41 and we expect that these cells will also enter the clinical arena.…”

“…The cellular approach includes a variety of cells, including neural stem and progenitor cells, cord blood, and mesenchymal stem cells (MSCs). [13][14][15][16][17][18] The search for pharmacological therapies that potentiate the recovery process after a neurological injury has intensified during the last decade. Many therapeutic agents already marketed have been shown to promote functional outcome after stroke, 7,19 -22 including trophic and growth factors (e.g., vascular endothelial cell growth factor (VEGF), basic fibroblast growth factor (bFGF), and BDNF), granulocyte colony-stimulating factor (G-CSF), angiopoietin 1 (ANG1), angiotensin modulators, minocycline, and thiazolidinediones.…”

Rescuing the neonatal brain from hypoxic injury with autologous cord blood

“…[89][90][91][92][93][94][95][96] Beneficial effects have generally been observed determined by behavioral improvements in most cases, but also by the reduction in lesion size in some studies. Owing to the poor survival of the transplanted cells and little evidence for neural differentiation, bystander effects have been postulated to be the main mechanisms for functional recovery after CB transplantation, including release of neurotrophic factors to stimulate endogenous neurogenesis, prevention of cell loss and immunomodulation (Figure 4).…”

Cell-Based and Exosome Therapy in Diabetic Stroke

“…HUCBC derived therapeutic effects are mainly derived from stimulation of endogenous brain repair mechanisms via parenchymal cell stimulation and release of trophic factors and modulation of inflammatory responses such as attenuating pro‐inflammatory T helper cell type 1 (Th1) response, amplifying anti‐inflammatory T‐helper 2 (Th2) response, decreasing pro‐inflammatory and increasing anti‐inflammatory cytokines, and macrophage polarization from pro‐inflammatory M1 to anti‐inflammatory M2 phenotype 18, 19, 46. In the ischemic brain parenchyma of rats subjected to stroke, HUCBC treatment significantly decreases infiltration of granulocytes and monocytes, and decreases astroglial and microglial activation 47. HUCBC treatment after stroke can also modulate peripheral immune responses and rescue stroke induced gross spleen size and CD8+ T‐cell number decrease which correlates with the extent of ischemic injury to the brain 48.…”