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Biodistribution of infused human umbilical cord blood cells in Alzheimer’s disease-like murine model

Bibliographic

Year of Publication:
2016
Contact PI Name:
Jared Ehrhart
Contact PI Affiliation:
Saneron CCEL Therapeutics, Inc, Tampa, Florida, USA
Co-Authors:
Donna Darlington, Nicole Kuzmin-Nichols, Cyndy D. Sanberg, Darrell R. Sawmiller, Paul R. Sanberg, Jun Tan
Primary Reference (PubMED ID):
Funding Source:
Florida Hi Tech Corridor Matching Grant Program
National Institute on Aging (NIA)
Study Goal and Principal Findings:

Human umbilical cord blood cells (HUCBCs), a prolific source of non-embryonic or adult stem cells, have emerged as effective and relatively safe immunomodulators and neuroprotectors, reducing behavioral impairment in animal models of Alzheimer’s disease (AD), Parkinson’s disease, amyotrophic lateral sclerosis, traumatic brain injury, spinal cord injury, and stroke. In this report, we followed the bioavailability of HUCBCs in AD-like transgenic PSAPP mice and nontransgenic Sprague–Dawley rats. HUCBCs were injected into tail veins of mice or rats at a single dose of 1 × 106 or 2.2 × 106 cells, respectively, prior to harvesting of tissues at 24 h, 7 days, and 30 days after injection. For determination of HUCBC distribution, tissues from both species were subjected to total DNA isolation and polymerase chain reaction (PCR) amplification of the gene for human glycerol-3-phosphate dehydrogenase. Our results show a relatively similar biodistribution and retention of HUCBCs in both mouse and rat organs. HUCBCs were broadly detected both in the brain and several peripheral organs, including the liver, kidney, and bone marrow, of both species, starting within 7 days and continuing up to 30 days posttransplantation. No HUCBCs were recovered in the peripheral circulation, even at 24 h posttransplantation. Therefore, HUCBCs reach several tissues including the brain following a single intravenous treatment, suggesting that this route can be a viable method of administration of these cells for the treatment of neurodegenerative diseases.

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
Species:
Rat
Model Type:
Outbred
Strain/Genetic Background:
Not Applicable
Animal Model Notes:
It is unclear which APPxPS1 transgenic mouse model is used in this study. The authors designate the model as PSAPP.

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
ADME
Biodistribution