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Peripherally administered human umbilical cord blood cells reduce parenchymal and vascular β-amyloid deposits in Alzheimer mice


Year of Publication:
Contact PI Name:
Jun Tan
Contact PI Affiliation:
Rashid Laboratory for Developmental Neurobiology Silver Child Development Center Department of Psychiatry and Behavioral Medicine College of Medicine, University of South Florida, Tampa, Florida, USA
W.V. Nikolic, H. Hou, T. Town, Y. Zhu, B. Giunta, C.D. Sanberg, J. Zeng, D. Luo, J. Ehrhart, T. Mori, P.R. Sanberg
Primary Reference (PubMED ID):
Funding Source:
Johnnie B. Byrd Alzheimer’s Center and Research Institute
National Institute on Aging (NIA)
National Institute of Neurological Disorders and Stroke (NINDS)
Cryo-Cell International Inc.
Saneron CCEL Therapeutic Inc.
Study Goal and Principal Findings:

Modulation of immune/inflammatory responses by diverse strategies including amyloid-β (Aβ) immunization, nonsteroidal anti-inflammatory drugs, and manipulation of microglial activation states has been shown to reduce Alzheimer’s disease (AD)-like pathology and cognitive deficits in AD transgenic mouse models. Human umbilical cord blood cells (HUCBCs) have unique immunomodulatory potential. This study tested whether these cells might alter AD-like pathology after infusion into the PSAPP mouse model of AD. Here, they report a marked reduction in Aβ levels/-amyloid plaques and associated astrocytosis following multiple low-dose infusions of HUCBCs. HUCBC infusions also reduced cerebral vascular Aβ deposits in the Tg2576 AD mouse model. Interestingly, these effects were associated with suppression of the CD40–CD40L interaction, as evidenced by decreased circulating and brain soluble CD40L (sCD40L), elevated systemic immunoglobulin M (IgM) levels, attenuated CD40L-induced inflammatory responses, and reduced surface expression of CD40 on microglia. Importantly, deficiency in CD40 abolishes the effect of HUCBCs on elevated plasma Aβ levels. Moreover, microglia isolated from HUCBC-infused PSAPP mice demonstrated increased phagocytosis of Aβ. Furthermore, sera from HUCBC-infused PSAPP mice significantly increased microglial phagocytosis of the Aβ1-42 peptide while inhibiting interferon--induced microglial CD40 expression. Increased microglial phagocytic activity in this scenario was inhibited by addition of recombinant CD40L protein. These data suggest that HUCBC infusion mitigates AD-like pathology by disrupting CD40L activity. 

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:
Model Type:
Strain/Genetic Background:
Not Reported
Model Type:
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
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


Outcome Measured
Outcome Parameters
beta Amyloid Deposits
beta Amyloid Load
Activated Astrocytes
Activated Microglia
Dense-core/Compact Plaques
Brain-beta Amyloid Deposits
Brain-Detergent Soluble beta Amyloid Peptide 40
Brain-Detergent Soluble beta Amyloid Peptide 42
Glial Fibrillary Acidic Protein (GFAP)
Soluble CD40 Ligand (sCD40L)
Interferon (IFN) gamma
Brain-beta Amyloid Deposits
beta Amyloid Load
Activated Astrocytes
Activated Microglia
Microglia Phagocytosis
Vascular beta Amyloid
Glial Fibrillary Acidic Protein (GFAP)
Plasma-beta Amyloid Peptide 40
Plasma-beta Amyloid Peptide 42