Abstract
BackgroundStem/progenitor cells (SPCs) demonstrate neuro-regenerative potential that is dependent upon their humoral activity by producing various trophic factors regulating cell migration, growth, and differentiation. Herein, we compared the expression of neurotrophins (NTs) and their receptors in specific umbilical cord blood (UCB) SPC populations, including lineage-negative, CD34+, and CD133+ cells, with that in unsorted, nucleated cells (NCs).Methods and ResultsThe expression of NTs and their receptors was detected by QRT-PCR, western blotting, and immunofluorescent staining in UCB-derived SPC populations (i.e., NCs vs. lineage-negative, CD34+, and CD133+ cells). To better characterize, global gene expression profiles of SPCs were determined using genome-wide RNA microarray technology. Furthermore, the intracellular production of crucial neuro-regenerative NTs (i.e., BDNF and NT-3) was assessed in NCs and lineage-negative cells after incubation for 24, 48, and 72 h in both serum and serum-free conditions. We discovered significantly higher expression of NTs and NT receptors at both the mRNA and protein level in lineage-negative, CD34+, and CD133+ cells than in NCs. Global gene expression analysis revealed considerably higher expression of genes associated with the production and secretion of proteins, migration, proliferation, and differentiation in lineage-negative cells than in CD34+ or CD133+ cell populations. Notably, after short-term incubation under serum-free conditions, lineage-negative cells and NCs produced significantly higher amounts of BDNF and NT-3 than under steady-state conditions. Finally, conditioned medium (CM) from lineage-negative SPCs exerted a beneficial impact on neural cell survival and proliferation.ConclusionsCollectively, our findings demonstrate that UCB-derived SPCs highly express NTs and their relevant receptors under steady-state conditions, NT expression is greater under stress-related conditions and that CM from SPCs favorable influence neural cell proliferation and survival. Understanding the mechanisms governing the characterization and humoral activity of subsets of SPCs may yield new therapeutic strategies that might be more effective in treating neurodegenerative disorders.
Highlights
Neurodegenerative diseases (NDs), such as amyotrophic lateral sclerosis, Alzheimer’s disease, Huntington’s disease, age-related macular degeneration, and Parkinson’s disease are characterized clinically by their subtle onset but chronic progression and involve the degeneration of defined neuronal phenotypes in the central nervous system (CNS)
Collectively, our findings demonstrate that umbilical cord blood (UCB)-derived stem/ progenitor cells (SPCs) highly express NTs and their relevant receptors under steady-state conditions, NT expression is greater under stress-related conditions and that conditioned medium (CM) from SPCs favorable influence neural cell proliferation and survival
Understanding the mechanisms governing the characterization and humoral activity of subsets of SPCs may yield new therapeutic strategies that might be more effective in treating neurodegenerative disorders
Summary
Neurodegenerative diseases (NDs), such as amyotrophic lateral sclerosis, Alzheimer’s disease, Huntington’s disease, age-related macular degeneration, and Parkinson’s disease are characterized clinically by their subtle onset but chronic progression and involve the degeneration of defined neuronal phenotypes in the central nervous system (CNS). Therapeutic approaches involving the transplantation of stem cells focuses primarily on the replacement of lost neurons and the restoration of neural tissue structure. These experimental studies demonstrate that UCB-derived cells are capable of surviving transplantation, convincing evidence that they are able to differentiate into mature neurons is lacking. The reported beneficial effects of stem cell-based therapy may depend on the trophic activity of producing various cytokines, including neurotrophins (NTs), which regulate the growth, differentiation, and migration of neural SPCs. In recent years, numerous studies have shown that stem cell transplantation elicits neurogenesis and angiogenesis by releasing neuroprotective factors (e.g., brainderived neurotrophic factor (BDNF) and nerve growth factor (NGF)) [10]. We compared the expression of neurotrophins (NTs) and their receptors in specific umbilical cord blood (UCB) SPC populations, including lineage-negative, CD34+, and CD133+ cells, with that in unsorted, nucleated cells (NCs)
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