Human Umbilical Cord Blood Cells Ameliorate Motor Deficits in Rabbits in a Cerebral Palsy Model.
Abstract
Cerebral palsy (CP) has a significant impact on both patients and society, but therapy
is limited. Human umbilical cord blood cells (HUCBC), containing various stem and
progenitor cells, have been used to treat various brain genetic conditions. In small
animal experiments, HUCBC have improved outcomes after hypoxic-ischemic (HI) injury.
Clinical trials using HUCBC are underway, testing feasibility, safety and efficacy
for neonatal injury as well as CP. We tested HUCBC therapy in a validated rabbit model
of CP after acute changes secondary to HI injury had subsided. Following uterine ischemia
at 70% gestation, we infused HUCBC into newborn rabbit kits with either mild or severe
neurobehavioral changes. Infusion of high-dose HUCBC (5 × 10(6) cells) dramatically
altered the natural history of the injury, alleviating the abnormal phenotype including
posture, righting reflex, locomotion, tone, and dystonia. Half the high dose showed
lesser but still significant improvement. The swimming test, however, showed that
joint function did not restore to naïve control function in either group. Tracing
HUCBC with either MRI biomarkers or PCR for human DNA found little penetration of
HUCBC in the newborn brain in the immediate newborn period, suggesting that the beneficial
effects were not due to cellular integration or direct proliferative effects but rather
to paracrine signaling. This is the first study to show that HUCBC improve motor performance
in a dose-dependent manner, perhaps by improving compensatory repair processes.
Type
Journal articleSubject
AnimalsRabbits
Humans
Cerebral Palsy
Hypoxia-Ischemia, Brain
Disease Models, Animal
Cord Blood Stem Cell Transplantation
Behavior, Animal
Motor Activity
Paracrine Communication
Pregnancy
Female
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https://hdl.handle.net/10161/24632Published Version (Please cite this version)
10.1159/000374107Publication Info
Drobyshevsky, Alexander; Cotten, C Michael; Shi, Zhongjie; Luo, Kehuan; Jiang, Rugang;
Derrick, Matthew; ... Tan, Sidhartha (2015). Human Umbilical Cord Blood Cells Ameliorate Motor Deficits in Rabbits in a Cerebral
Palsy Model. Developmental neuroscience, 37(4-5). pp. 349-362. 10.1159/000374107. Retrieved from https://hdl.handle.net/10161/24632.This is constructed from limited available data and may be imprecise. To cite this
article, please review & use the official citation provided by the journal.
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Show full item recordScholars@Duke
Charles Michael Cotten
Professor of Pediatrics
I am involved in 4 major areas of research: 1) Neuroprotection. Working with colleagues
from Cell Therapies, we have added to Duke's experience participating in pivotal trials
of hypothermia for term newborns with moderate to severe hypoxic-ischemic encephalopathy
(HIE) by completing a phase I study of autologous cord blood cells for these infants,
and developing and currently leading a multicenter, double-blind randomized clinical
trial of autologous cord blood cells or placebo in te
Ronald Norman Goldberg
Professor Emeritus of Pediatrics
1. Perinatal asphyxia and neuroprotection - use of umbilical cord blood transfusion
2. Persistent Pulmonary hypertension - use of ethyl nitrite 3. The extremely low-birth-weight
infant. 4. Newborn screening - use of digital microfluidics
Joanne Kurtzberg
Jerome S. Harris Distinguished Professor of Pediatrics
Dr. Kurtzberg is an internationally renowned expert in pediatric hematology/oncology,
pediatric blood and marrow transplantation, umbilical cord blood banking and transplantation,
and novel applications of cord blood and birthing tissues in the emerging fields of
cellular therapies and regenerative medicine. Dr. Kurtzberg serves as the Director
of the Marcus Center for Cellular Cures (MC3), Director of the Pediatric Transplant
and Cellular Therapy Program, Director of the Carolina
Elisabeth Tomlinson Tracy
Assistant Professor of Surgery
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