A single administration of human umbilical cord blood T cells produces long-lasting effects in the aging hippocampus

Abstract

Neurogenesis occurs throughout life but significantly decreases with age. Human umbilical cord blood mononuclear cells (HUCB MNCs) have been shown to increase the proliferation of neural stem cells (NSCs) in the dentate gyrus (DG) of the hippocampus and the subgranular zone of aging rats (Bachstetter et al., BMC Neurosci 9:22, 2008), but it is unclear which fraction or combination of the HUCB MNCs are responsible for neurogenesis. To address this issue, we examined the ability of HUCB MNCs, CD4+, CD8+, CD3+, CD14+, and CD133+ subpopulations to increase proliferation of NSCs both in vitro and in vivo. NSCs were first grown in conditioned media generated from HUCB cultures, and survival and proliferation of NSC were determined with the fluorescein diacetate/propidium iodide and 5-bromo-2′-deoxyuridine incorporation assays, respectively. In a second study, we injected HUCB cells intravenously in young and aged Fisher 344 rats and examined proliferation in the DG at 1 week (study 2.1) and 2 weeks (study 2.2) postinjection. The effects of the HUCB MNC fractions on dendritic spine density and microglial activation were also assessed. HUCB T cells (CD3+, CD4+, and CD8+ cells) induced proliferation of NSCs (p < 0.001) and increased cell survival. In vivo, HUCB-derived CD4+ cells increased NSC proliferation at both 1 and 2 weeks while also enhancing the density of dendritic spines at 1 week and decreasing inflammation at 2 weeks postinjection. Collectively, these data indicate that a single injection of HUCB-derived T cells induces long-lasting effects and may therefore have tremendous potential to improve aging neurogenesis.

Nutraceutical intervention reverses the negative effects of blood from aged rats on stem cells

“…One study used umbilical cord blood demonstrating that a single injection was sufficient to increase neurogenesis in aged rats (Bachstetter et al 2008). A follow-up study examined which cells within the umbilical cord blood might be responsible, and it was suggested that naïve T cells were the fraction responsible for this effect (Shahaduzzaman et al 2013). Thus, it is clear that multiple factors and cells within young/ neonatal blood may have beneficial effects on the stem cell niches of aged subjects.…”

Cord Blood as a Treatment for Stroke

“…Almost all of the studies in the adult are in younger adults and not the aged. While the cells have a demonstrated ability to increase proliferation in the subgranular zone of the hippocampus and increase density of dendritic spines (Bachstetter et al 2008;Shahaduzzaman et al 2013) in the aged rat, they have not yet been shown to improve stroke outcome in an aged animal.…”

“…The cells also produce a number of molecules that are essential for the interaction of the cells with other cells and extracellular matrix, including E-selectin, L-selectin, intercellular adhesion molecule (ICAM), and vascular adhesion molecule (VCAM). While these adhesion molecules are essential for the trafficking of the UCB immune cells from the blood stream into the tissue, they may also be responsible for the ability of the UCB cells to enhance neuritic outgrowth in culture ) and stimulate dendritic growth in other animal models of CNS aging or disease (Shahaduzzaman et al 2013;Willing et al In Press).…”

Translating G-CSF as an Adjunct Therapy to Stem Cell Transplantation for Stroke

“…Furthermore, treatment with G-CSF has been shown to modulate neurogenesis in TBI and in other neurodegenerative disorders (e.g., hypoxic injury, Alzheimer’s disease, etc.) [75,77]. Our histological studies indicated that concomitant with functional improvement, adjunct treatment of G-CSF and hUCB resulted in more pronounced reduction of TBI-induced upregulation of MHCII + cells (putatively activated microglia) in the cortex, striatum, thalamus, SVZ, and the dentate gyrus (DG) of the hippocampus, compared with hUCB and/or G-CSF monotherapy [73].…”