Human adipose tissue‐derived mesenchymal stem cells improve cognitive function and physical activity in ageing mice

Abstract

Brain ageing leads to atrophy and degeneration of the cholinergic nervous system, resulting in profound neurobehavioral and cognitive dysfunction from decreased acetylcholine biosynthesis and reduced secretion of growth and neurotrophic factors. Human adipose tissue-derived mesenchymal stem cells (ADMSCs) were intravenously (1 3 10 6 cells) or intracerebroventricularly (4 3 10 5 cells) transplanted into the brains of 18-month-old mice once or four times at 2-week intervals. Transplantation of ADMSCs improved both locomotor activity and cognitive function in the aged animals, in parallel with recovery of acetylcholine levels in brain tissues. Transplanted cells differentiated into neurons and, in part, into astrocytes and produced choline acetyltransferase proteins. Transplantation of ADMSCs restored microtubule-associated protein 2 in brain tissue and enhanced Trk B expression and the concentrations of brain-derived neurotrophic factor and nerve growth factor. These results indicate that human ADMSCs differentiate into neural cells in the brain microenvironment and can restore physical and cognitive functions of aged mice not only by increasing acetylcholine synthesis but also by restoring neuronal integrity that may be mediated by growth/neurotrophic factors. V V C 2013 Wiley Periodicals, Inc.

Cell-based therapy in Alzheimer's disease: Current knowledge and perspective

“…Transplantation of human adipose tissuederived MSCs improved both locomotor activity and cognitive function in the aged animals, in parallel with the recovery of acetylcholine levels in brain tissues, which was accomplished by enhancing the concentrations of brain-derived neurotrophic factor (BDNF), nerve growth factor (NGF) [41] , and vascular endothelial growth factor (VEGF) [42] . Aβ increases NSPC activity [43] , which may be a natural reaction against toxicity induced by AD.…”

“…Furthermore, AD animal models have provided evidence that a shortage of NGF supply may induce an AD-like syndrome [75] . Human adipose tissuederived MSCs could enhance the concentrations of BDNF and NGF, which could lead to an improvement in cognitive function [41] . Another group have shown that MSCs significantly attenuated memory deficits and neuropathology, by up-regulating cytokine interleukin (IL)-10 and VEGF [42] .…”

Neural stem cells could serve as a therapeutic material for age-related neurodegenerative diseases

“…In addition, a recent study demonstrated that human mesenchymal stem cells can enhance autophagy in amyloid β-treated neurons and mice, thus promoting amyloid β clearance and increasing neuronal survival against amyloid β toxicity [66] . Transplantation of human adipose tissuederived mesenchymal stem cells into the brains of aged mice enhance the levels of Ach, and consequently improve the cognitive and locomotor functions of the mice [67] . Interestingly, it was studied that ChAT-positive neurons could be directly generated from mesenchymal stem cells.…”

Stem cell treatment for age-related neurodegenerative diseases

“…In addition, a recent study demonstrated that human MSCs can enhance autophagy in amyloid β-treated neurons and mice, thus promoting amyloid β clearance and increasing neuronal survival against amyloid β toxicity [50]. Transplantation of human adipose tissue-derived MSCs into the brains of aged mice enhance the levels of acetyltransferase, thereby significantly improve the cognitive ability and locomotor functions of the mice [51]. Furthermore, in patients with AD reduced number of circulating HSCs (CD34+ cells) were found [52].…”