Autologous Bone Marrow Mononuclear Cells Exert Broad Effects on Short- and Long-Term Biological and Functional Outcomes in Rodents with Intracerebral Hemorrhage

Abstract

Autologous bone marrow-derived mononuclear cells (MNCs) are a potential therapy for ischemic stroke. However, the effect of MNCs in intracerebral hemorrhage (ICH) has not been fully studied. In this study, we investigated the effects of autologous MNCs in experimental ICH. ICH was induced by infusion of autologous blood into the left striatum in young and aged male Long Evans rats. Twenty-four hours after ICH, rats were randomized to receive an intravenous administration of autologous MNCs (1 · 10 7 cells/kg) or saline. We examined brain water content, various markers related to the integrity of the neurovascular unit and inflammation, neurological deficit, neuroregeneration, and brain atrophy. We found that MNC-treated young rats showed a reduction in the neurotrophil infiltration, the number of inducible nitric oxide synthase-positive cells, and the expression of inflammatory-related signalings such as the high-mobility group protein box-1, S100 calcium binding protein B, matrix metalloproteinase-9, and aquaporin 4. Ultimately, MNCs reduced brain edema in the perihematomal area compared with saline-treated animals at 3 days after ICH. Moreover, MNCs increased vessel density and migration of doublecortin-positive cells, improved motor functional recovery, spatial learning, and memory impairment, and reduced brain atrophy compared with saline-treated animals at 28 days after ICH. We also found that MNCs reduced brain edema and brain atrophy and improved spatial learning and memory in aged rats after ICH. We conclude that autologous MNCs can be safely harvested and intravenously reinfused in rodent ICH and may improve long-term structural and functional recovery after ICH. The results of this study may be applicable when considering future clinical trials testing MNCs for ICH.

Treatment of Severe Adult Traumatic Brain Injury Using Bone Marrow Mononuclear Cells

“…These positive effects on functional outcomes have been replicated in various animal stroke models as well [3]. Similarly, in both injury models, BMMNCs dampen the secondary neuroinflammatory response to injury [4][5][6]. Finally, there appears to be a consistent treatment window of 24-72 hours [7].…”

Outcomes of Bone Marrow Mononuclear Cell Transplantation for Neurological Sequelae Due to Intracranial Hemorrhage Incidence in the Neonatal Period: Report of Four Cases

“…To improve neurological sequelae after intra-ventricular hemorrhage, many research efforts using stem cells have been carried out in animals (30)(31)(32). Ahn et al performed intra-ventricular transplantation of umbilical cord bloodderived mesenchymal stem cells (MSCs) for induced intraventricular hemorrhage in Newborn Sprague-Dawley rats.…”

“…Bolisetty et al showed that infants born at 23 to 28 weeks' gestation with grade III-IV intra-ventricular hemorrhage had high rates of developmental delay (17.5%), cerebral palsy (30%), deafness (8.6%), and blindness (2.2%) (2). According to Pierrat et al, the overall rate of cerebral palsy in infants born at [24][25][26][27][28][29][30][31], and 32-34 weeks of gestation was 6.9, 4.3, and 1%, respectively (14).…”

Autologous bone marrow-derived mononuclear cell therapy in three patients with severe asthma​

“…A peripheral vein was used for BMMC transplantation, since the procedure could be easily performed without the need of intubation for bronchoscopy. Intravenous administration has demonstrated a good safety profile for delivery of either BMMCs or MSCs in experimental models [6,7,9,[16][17][18][19]. Even though a systemic route was used in the cases described herein, these cells are efficiently delivered to the lungs, as they are subject to a first-pass effect [20].…”