title: 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.
authors: Department of Pediatrics, NorthShore University HealthSystem, Evanston, Ill., USA.
authors: Alexander
authors: A
authors: Drobyshevsky
authors: C Michael
authors: CM
authors: Cotten
authors: Zhongjie
authors: Z
authors: Shi
authors: Kehuan
authors: K
authors: Luo
authors: Rugang
authors: R
authors: Jiang
authors: Matthew
authors: M
authors: Derrick
authors: Elizabeth T
authors: ET
authors: Tracy
authors: Tracy
authors: T
authors: Gentry
authors: Ronald N
authors: RN
authors: Goldberg
authors: Joanne
authors: J
authors: Kurtzberg
authors: Sidhartha
authors: S
authors: Tan
mesh_terms: D000818:Animals; D001522:Behavior, Animal / Q000502:physiology; D002547:Cerebral Palsy / Q000209:etiology / Q000628:therapy*; D036101:Cord Blood Stem Cell Transplantation / Q000379:methods*; D004195:Disease Models, Animal; D005260:Female; D006801:Humans; D020925:Hypoxia-Ischemia, Brain / Q000150:complications*; D009043:Motor Activity / Q000502:physiology*; D019899:Paracrine Communication; D011247:Pregnancy; D011817:Rabbits