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Human umbilical cord stem cell xenografts improve cognitive decline and reduce the amyloid burden in a mouse model of Alzheimer’s disease

Bibliographic

Year of Publication:
2017
Contact PI Name:
Thomas Wisniewski
Contact PI Affiliation:
New York University Langone Medical Center, Department of Neurology, School of Medicine, New York, New York, USA
Co-Authors:
Allal Boutajangout, Abdulwahab Noorwali, Hazem Atta
Primary Reference (PubMED ID):
Funding Source:
Deanship of Scientific Research King Abdulaziz University Jeddah Kingdom of Saudi Arabia
National Institute on Aging (NIA)
National Institute of Neurological Disorders and Stroke (NINDS)
Study Goal and Principal Findings:

Alzheimer’s disease (AD) is the most common cause of dementia. The search for new treatments is made more urgent given its increasing prevalence resulting from the aging of the global population. Over the past 20 years, stem cell technologies have become an increasingly attractive option to both study and potentially treat neurodegenerative diseases. Several investigators reported a beneficial effect of different types of stem or progenitor cells on the pathology and cognitive function in AD models. Mouse models are one of the most important research tools for finding new treatment for AD. This study aimed to explore the possible therapeutic potential of human umbilical cord mesenchymal stem cell xenografts in a transgenic (Tg) mouse model of AD. APP/PS1 Tg AD model mice received human umbilical cord stem cells, directly injected into the carotid artery. To test the efficacy of the umbilical cord stem cells in this AD model, behavioral tasks (sensorimotor and cognitive tests) and immunohistochemical quantitation of the pathology was performed. Treatment of the APP/PS1 AD model mice, with human umbilical cord stem cells, produced a reduction of the amyloid beta burden in the cortex and the hippocampus which correlated with a reduction of the cognitive loss. Human umbilical cord mesenchymal stem cells appear to reduce AD pathology in a transgenic mouse model as documented by a reduction of the amyloid plaque burden compared to controls. This amelioration of pathology correlates with improvements on cognitive and sensorimotor tasks.

Therapeutic Agent

Therapeutic Information:
Therapy Type:
Biologic - Cell-based
Therapeutic Agent:
Human Umbilical Cord Blood Cells (HUCBC)
Therapeutic Target:
Multi Target

Animal Model

Model Information:
Species:
Mouse
Model Type:
APPxPS1
Strain/Genetic Background:
Not Reported

Experimental Design

Is the following information reported in the study?:
Power/Sample Size Calculation
Randomized into Groups
Blinded for Treatment
Blinded for Outcome Measures
Pharmacokinetic Measures
Pharmacodynamic Measures
Toxicology Measures
ADME Measures
Biomarkers
Dose
Formulation
Route of Delivery
Duration of Treatment
Frequency of Administration
Age of Animal at the Beginning of Treatment
Age of Animal at the End of Treatment
Sex as a Biological Variable
Study Balanced for Sex as a Biological Variable
Number of Premature Deaths
Number of Excluded Animals
Statistical Plan
Genetic Background
Inclusion/Exclusion Criteria Included
Conflict of Interest

Outcomes

Outcome Measured
Outcome Parameters
Behavioral
Object Place Recognition
Motor Function
Rotarod Test
Locomotor Activity
Histopathology
beta Amyloid Deposits
Activated Astrocytes
Activated Microglia
Immunochemistry
Glial Fibrillary Acidic Protein (GFAP)
Ionized Calcium Binding Adaptor Molecule 1 (Iba1)
Cell Biology
Engrafted Stem Cells