{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,25]],"date-time":"2026-08-25T05:49:15Z","timestamp":1787636955496,"version":"build-2736575974"},"reference-count":55,"publisher":"Oxford University Press (OUP)","issue":"12","license":[{"start":{"date-parts":[[2023,9,29]],"date-time":"2023-09-29T00:00:00Z","timestamp":1695945600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"funder":[{"name":"Boston Children\u2019s Health Physicians\u2019 Neonatal Division"},{"name":"Touro Universities System"},{"DOI":"10.13039\/100000902","name":"Pediatric Cancer Research Foundation","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100000902","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2023,12,18]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>Intraventricular hemorrhage (IVH) is a severe complication of preterm birth associated with white matter injury (WMI) and reduced neurogenesis. IVH commonly arises from the germinal matrix, a highly cellular, transient structure, where all precursor cells are born, proliferate, and migrate during brain development. IVH leads to reduced progenitor cell proliferation and maturation and contributes to WMI. Interruption of oligodendrocyte lineage (OL) proliferation and maturation after IVH will prevent myelination. We evaluated whether unrestricted somatic stem cells (USSCs) could recover OL lineage, as USSC release multiple relevant growth factors and cytokines. The effects of USSC infusion at 24 hours after IVH were assessed in the periventricular zone by analysis of OL lineage-specific progression (PDGFR+, OLIG2+, NKX2.2+ with Ki67), and this was correlated with growth factors TGF\u03b21, FGF2 expression. The early OL cell lineage by immunofluorescence and cell density quantitation showed significant reduction after IVH (P\u2005&amp;lt;\u2005.05 both PDGFR+, OLIG2+ at day 3); with significant recovery after injection of USSCs (P\u2005&amp;lt;\u2005.05 both PDGFR+, OLIG2+ at day 3). CSF protein and tissue mRNA levels of TGF\u03b21 were reduced by IVH and recovered after USSC (P\u2005&amp;lt;\u2005.05 for all changes). FGF2 showed an increased mRNA after USSC on day3 (P\u2005&amp;lt;\u2005.05). Cell cyclin genes were unaffected except for the cycle inhibitor P27Kip1 which increased after IVH but returned to normal after USSC on day 3. Our findings demonstrated a plausible mechanism through which USSCs can aid in developmental myelination by recovery of OL proliferation and maturation along with correlative changes in growth factors during brain development.<\/jats:p>","DOI":"10.1093\/stcltm\/szad064","type":"journal-article","created":{"date-parts":[[2023,9,29]],"date-time":"2023-09-29T21:18:44Z","timestamp":1696022324000},"page":"811-824","source":"Crossref","is-referenced-by-count":11,"title":["Early Postnatal Expression of Tgf\u03b2-1 and Fgf-2 Correlates With Regenerative Functions of Unrestricted Somatic Stem Cell Infusion After Rabbit GMH-IVH"],"prefix":"10.1093","volume":"12","author":[{"given":"Dina A","family":"Finkel","sequence":"first","affiliation":[{"name":"Department of Pediatrics, The Regional Neonatal Center, Maria Fareri Children\u2019s Hospital at Westchester Medical Center, Division of Newborn Medicine, New York Medical College , Valhalla, NY , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ana","family":"Malfa","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, The Regional Neonatal Center, Maria Fareri Children\u2019s Hospital at Westchester Medical Center, Division of Newborn Medicine, New York Medical College , Valhalla, NY , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yanling","family":"Liao","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, New York Medical College , Valhalla, NY , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Deepti","family":"Purohit","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, The Regional Neonatal Center, Maria Fareri Children\u2019s Hospital at Westchester Medical Center, Division of Newborn Medicine, New York Medical College , Valhalla, NY , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Furong","family":"Hu","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, New York Medical College , Valhalla, NY , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Davud","family":"Sulaymankhil","sequence":"additional","affiliation":[{"name":"Department of Chemical Engineering, Cooper Union, NYC , NY , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sai","family":"Abhishek Narra","sequence":"additional","affiliation":[{"name":"Cell Biology & Anatomy, New York Medical College , Valhalla, NY , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Karen","family":"Hussein","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, The Regional Neonatal Center, Maria Fareri Children\u2019s Hospital at Westchester Medical Center, Division of Newborn Medicine, New York Medical College , Valhalla, NY , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Selvakumar","family":"Subbian","sequence":"additional","affiliation":[{"name":"Department of Medicine, Public Health Research Institute, New Jersey Medical School, Rutgers, The State University of Newark , NJ , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mitchell S","family":"Cairo","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, New York Medical College , Valhalla, NY , USA"},{"name":"Departments of Medicine, Pathology, Microbiology & Immunology, New York Medical College , Valhalla, NY , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6065-3092","authenticated-orcid":false,"given":"Govindaiah","family":"Vinukonda","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, New York Medical College , Valhalla, NY , USA"},{"name":"Cell Biology & Anatomy, New York Medical College , Valhalla, NY , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Edmund F","family":"La Gamma","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, The Regional Neonatal Center, Maria Fareri Children\u2019s Hospital at Westchester Medical Center, Division of Newborn Medicine, New York Medical College , Valhalla, NY , USA"},{"name":"Department of Pediatrics, New York Medical College , Valhalla, NY , USA"},{"name":"Department of Biochemistry and Molecular Biology, New York Medical College , NY , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2023,9,29]]},"reference":[{"key":"2023121811521936500_CIT0001","first-page":"1302","article-title":"Late oligodendrocyte progenitors coincide with the developmental window of vulnerability for human perinatal white matter injury","volume-title":"J Neurosci","author":"Back","year":"2001"},{"key":"2023121811521936500_CIT0002","first-page":"12068","article-title":"Bone morphogenetic protein inhibition promotes neurological recovery after intraventricular hemorrhage","volume-title":"J Neurosci","author":"Dummula","year":"2011"},{"key":"2023121811521936500_CIT0003","first-page":"617","article-title":"Neuropathologic findings in short-term survivors of intraventricular hemorrhage","volume-title":"Am J Dis Child","author":"Armstrong","year":"1987"},{"key":"2023121811521936500_CIT0004","first-page":"129","article-title":"Perinatal white matter injury: the changing spectrum of pathology and emerging insights into pathogenetic mechanisms","volume-title":"Ment Retard Dev Disabil Res Rev","author":"Back","year":"2006"},{"key":"2023121811521936500_CIT0005","first-page":"265","article-title":"Neural stem cells confer unique pinwheel architecture to the ventricular surface in neurogenic regions of the adult brain","volume-title":"Cell Stem Cell","author":"Mirzadeh","year":"2008"},{"key":"2023121811521936500_CIT0006","first-page":"197","article-title":"Endogenous progenitors remyelinate demyelinated axons in the adult CNS","volume-title":"Neuron","author":"Gensert","year":"1997"},{"key":"2023121811521936500_CIT0007","first-page":"247","article-title":"Increased expression of Nkx2.2 and Olig2 identifies reactive oligodendrocyte progenitor cells responding to demyelination in the adult CNS","volume-title":"Mol Cell Neurosci","author":"Fancy","year":"2004"},{"key":"2023121811521936500_CIT0008","first-page":"4357","article-title":"Progenitor cells of the adult mouse subventricular zone proliferate, migrate and differentiate into oligodendrocytes after demyelination","volume-title":"Eur J Neurosci","author":"Nait-Oumesmar","year":"1999"},{"key":"2023121811521936500_CIT0009","first-page":"13211","article-title":"Experimental autoimmune encephalomyelitis mobilizes neural progenitors from the subventricular zone to undergo oligodendrogenesis in adult mice","volume-title":"Proc Natl Acad Sci U S A","author":"Picard-Riera","year":"2002"},{"key":"2023121811521936500_CIT0010","first-page":"7907","article-title":"Origin of oligodendrocytes in the subventricular zone of the adult brain","volume-title":"J Neurosci","author":"Menn","year":"2006"},{"key":"2023121811521936500_CIT0011","first-page":"653","article-title":"Neurogenesis at the brain-cerebrospinal fluid interface","volume-title":"Annu Rev Cell Dev Biol","author":"Lehtinen","year":"2011"},{"key":"2023121811521936500_CIT0012","first-page":"889","article-title":"Cooperation between PDGF and FGF converts slowly dividing O-2Aadult progenitor cells to rapidly dividing cells with characteristics of O-2Aperinatal progenitor cells","volume-title":"J Cell Biol","author":"Wolswijk","year":"1992"},{"key":"2023121811521936500_CIT0013","first-page":"16","article-title":"Oligodendrocyte-type-2 astrocyte (O-2A) progenitor cells derived from adult rat spinal cord: in 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Res","author":"Diemel","year":"2003"},{"key":"2023121811521936500_CIT0018","first-page":"153","article-title":"Distinctive patterns of PDGF-A, FGF-2, IGF-I, and TGF-beta1 gene expression during remyelination of experimentally-induced spinal cord demyelination","volume-title":"Mol Cell Neurosci","author":"Hinks","year":"1999"},{"key":"2023121811521936500_CIT0019","first-page":"480","article-title":"IGF-I and FGF-2 coordinately enhance cyclin D1 and cyclin E-cdk2 association and activity to promote G1 progression in oligodendrocyte progenitor cells","volume-title":"Mol Cell Neurosci","author":"Frederick","year":"2004"},{"key":"2023121811521936500_CIT0020","first-page":"414","article-title":"IGF-I synergizes with FGF-2 to stimulate oligodendrocyte progenitor entry into the cell cycle","volume-title":"Dev Biol","author":"Jiang","year":"2001"},{"key":"2023121811521936500_CIT0021","first-page":"263","article-title":"Regulation of FGF receptors in the oligodendrocyte 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Hematol","author":"Kogler","year":"2005"},{"key":"2023121811521936500_CIT0037","first-page":"681","article-title":"Transplantation of human umbilical cord blood-derived adherent progenitors into the developing rodent brain","volume-title":"J Neuropathol Exp Neurol.","author":"Coenen","year":"2005"},{"key":"2023121811521936500_CIT0038","first-page":"1157","article-title":"Human cord blood-derived unrestricted somatic stem cell infusion improves neurobehavioral outcome in a rabbit model of intraventricular hemorrhage","volume-title":"Stem Cells Transl Med","author":"Vinukonda","year":"2019"},{"key":"2023121811521936500_CIT0039","first-page":"633185","article-title":"Human cord blood derived unrestricted somatic stem cells restore aquaporin channel expression, reduce inflammation and inhibit the development of hydrocephalus after experimentally induced perinatal intraventricular hemorrhage","volume-title":"Front Cell Neurosci","author":"Purohit","year":"2021"},{"key":"2023121811521936500_CIT0040","first-page":"431","article-title":"Significant clinical, neuropathological and behavioural recovery from acute spinal cord trauma by transplantation of a well-defined somatic stem cell from human umbilical cord blood","volume-title":"Brain","author":"Schira","year":"2012"},{"key":"2023121811521936500_CIT0041","first-page":"123","article-title":"A new human somatic stem cell from placental cord blood with intrinsic pluripotent differentiation potential","volume-title":"J Exp Med","author":"Kogler","year":"2004"},{"key":"2023121811521936500_CIT0042","first-page":"303","article-title":"Human cord blood-derived unrestricted somatic stem cells promote wound healing and have therapeutic potential for patients with recessive dystrophic epidermolysis bullosa","volume-title":"Cell Transplant","author":"Liao","year":"2014"},{"key":"2023121811521936500_CIT0043","first-page":"3378","article-title":"Characterization 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