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Human Cord Blood-Derived Unrestricted Somatic Stem Cell Infusion Improves Neurobehavioral Outcome in a Rabbit Model of Intraventricular Hemorrhage.

Abstract

Intraventricular hemorrhage (IVH) is a severe complication of preterm birth, which leads to hydrocephalus, cerebral palsy, and mental retardation. There are no available therapies to cure IVH and standard treatment is supportive care. Unrestricted somatic stem cells (USSCs) from human cord blood have reparative effects in animal models of brain and spinal cord injuries. USSCs were administered to premature rabbit pups with IVH and their effects on white matter integrity and neurobehavioral performance were evaluated. USSCs were injected either via intracerebroventricular (ICV) or via intravenous (IV) routes in 3 days premature (term 32d) rabbit pups, 24 hours after glycerol-induced IVH. The pups were sacrificed at postnatal days 3, 7, and 14 and effects were compared to glycerol-treated but unaffected or nontreated control. Using in vivo live bioluminescence imaging and immunohistochemical analysis, injected cells were found in the injured parenchyma on day 3 when using the IV route compared to ICV where cells were found adjacent to the ventricle wall forming aggregates; we did not observe any adverse events from either route of administration. The injected USSCs were functionally associated with attenuated microglial infiltration, less apoptotic cell death, fewer reactive astrocytes, and diminished levels of key inflammatory cytokines (TNFα and IL1β). In addition, we observed better preservation of myelin fibers, increased myelin gene expression, and altered reactive astrocyte distribution in treated animals, and this was associated with improved locomotor function. Overall, our findings support the possibility that USSCs exert anti-inflammatory effects in the injured brain mitigating many detrimental consequences associated with IVH. Stem Cells Translational Medicine 2019.

Authors+Show Affiliations

Department of Pediatrics, New York Medical College, Valhalla, New York, USA. Cell Biology & Anatomy, New York Medical College, Valhalla, New York, USA.Department of Pediatrics, New York Medical College, Valhalla, New York, USA.Department of Pediatrics, New York Medical College, Valhalla, New York, USA.Department of Pediatrics, New York Medical College, Valhalla, New York, USA.The Regional Neonatal Center at Maria Fareri Children's Hospital of Westchester Medical Center, Valhalla, New York, USA.The Regional Neonatal Center at Maria Fareri Children's Hospital of Westchester Medical Center, Valhalla, New York, USA.The Regional Neonatal Center at Maria Fareri Children's Hospital of Westchester Medical Center, Valhalla, New York, USA.Cell Biology & Anatomy, New York Medical College, Valhalla, New York, USA.Department of Pediatrics, New York Medical College, Valhalla, New York, USA. The Regional Neonatal Center at Maria Fareri Children's Hospital of Westchester Medical Center, Valhalla, New York, USA.The Regional Neonatal Center at Maria Fareri Children's Hospital of Westchester Medical Center, Valhalla, New York, USA.Department of Pediatrics, New York Medical College, Valhalla, New York, USA. The Regional Neonatal Center at Maria Fareri Children's Hospital of Westchester Medical Center, Valhalla, New York, USA.Department of Pediatrics, New York Medical College, Valhalla, New York, USA. Cell Biology & Anatomy, New York Medical College, Valhalla, New York, USA. Department of Medicine, Pathology, Microbiology & Immunology, Cell Biology & Anatomy, New York Medical College, Valhalla, New York, USA.Department of Pediatrics, New York Medical College, Valhalla, New York, USA. The Regional Neonatal Center at Maria Fareri Children's Hospital of Westchester Medical Center, Valhalla, New York, USA. Department of Biochemistry and Molecular Biology, New York Medical College, Valhalla, New York, USA.

Pub Type(s)

Journal Article

Language

eng

PubMed ID

31322326

Citation

Vinukonda, Govindaiah, et al. "Human Cord Blood-Derived Unrestricted Somatic Stem Cell Infusion Improves Neurobehavioral Outcome in a Rabbit Model of Intraventricular Hemorrhage." Stem Cells Translational Medicine, 2019.
Vinukonda G, Liao Y, Hu F, et al. Human Cord Blood-Derived Unrestricted Somatic Stem Cell Infusion Improves Neurobehavioral Outcome in a Rabbit Model of Intraventricular Hemorrhage. Stem Cells Transl Med. 2019.
Vinukonda, G., Liao, Y., Hu, F., Ivanova, L., Purohit, D., Finkel, D. A., ... La Gamma, E. F. (2019). Human Cord Blood-Derived Unrestricted Somatic Stem Cell Infusion Improves Neurobehavioral Outcome in a Rabbit Model of Intraventricular Hemorrhage. Stem Cells Translational Medicine, doi:10.1002/sctm.19-0082.
Vinukonda G, et al. Human Cord Blood-Derived Unrestricted Somatic Stem Cell Infusion Improves Neurobehavioral Outcome in a Rabbit Model of Intraventricular Hemorrhage. Stem Cells Transl Med. 2019 Jul 19; PubMed PMID: 31322326.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Human Cord Blood-Derived Unrestricted Somatic Stem Cell Infusion Improves Neurobehavioral Outcome in a Rabbit Model of Intraventricular Hemorrhage. AU - Vinukonda,Govindaiah, AU - Liao,Yanling, AU - Hu,Furong, AU - Ivanova,Larisa, AU - Purohit,Deepti, AU - Finkel,Dina A, AU - Giri,Priyadarshani, AU - Bapatla,Lakshmipramoda, AU - Shah,Shetal, AU - Zia,Muhammed T, AU - Hussein,Karen, AU - Cairo,Mitchell S, AU - La Gamma,Edmund F, Y1 - 2019/07/19/ PY - 2019/03/15/received PY - 2019/06/24/accepted PY - 2019/7/20/entrez KW - Bioluminescence imaging KW - Intraventricular hemorrhage KW - Locomotor function KW - Myelination KW - Unrestricted somatic stem cells (USSCs) KW - White matter injury JF - Stem cells translational medicine JO - Stem Cells Transl Med N2 - Intraventricular hemorrhage (IVH) is a severe complication of preterm birth, which leads to hydrocephalus, cerebral palsy, and mental retardation. There are no available therapies to cure IVH and standard treatment is supportive care. Unrestricted somatic stem cells (USSCs) from human cord blood have reparative effects in animal models of brain and spinal cord injuries. USSCs were administered to premature rabbit pups with IVH and their effects on white matter integrity and neurobehavioral performance were evaluated. USSCs were injected either via intracerebroventricular (ICV) or via intravenous (IV) routes in 3 days premature (term 32d) rabbit pups, 24 hours after glycerol-induced IVH. The pups were sacrificed at postnatal days 3, 7, and 14 and effects were compared to glycerol-treated but unaffected or nontreated control. Using in vivo live bioluminescence imaging and immunohistochemical analysis, injected cells were found in the injured parenchyma on day 3 when using the IV route compared to ICV where cells were found adjacent to the ventricle wall forming aggregates; we did not observe any adverse events from either route of administration. The injected USSCs were functionally associated with attenuated microglial infiltration, less apoptotic cell death, fewer reactive astrocytes, and diminished levels of key inflammatory cytokines (TNFα and IL1β). In addition, we observed better preservation of myelin fibers, increased myelin gene expression, and altered reactive astrocyte distribution in treated animals, and this was associated with improved locomotor function. Overall, our findings support the possibility that USSCs exert anti-inflammatory effects in the injured brain mitigating many detrimental consequences associated with IVH. Stem Cells Translational Medicine 2019. SN - 2157-6580 UR - https://www.unboundmedicine.com/medline/citation/31322326/Human_Cord_Blood-Derived_Unrestricted_Somatic_Stem_Cell_Infusion_Improves_Neurobehavioral_Outcome_in_a_Rabbit_Model_of_Intraventricular_Hemorrhage L2 - https://doi.org/10.1002/sctm.19-0082 DB - PRIME DP - Unbound Medicine ER -