NYMC Faculty Publications

Early Postnatal Expression of Tgfβ-1 and Fgf-2 Correlates With Regenerative Functions of Unrestricted Somatic Stem Cell Infusion After Rabbit GMH-IVH

Dina A. Finkel, Department of Pediatrics, The Regional Neonatal Center, Maria Fareri Children's Hospital at Westchester Medical Center, Division of Newborn Medicine, New York Medical College, Valhalla, NY, USA.
Ana Malfa, Department of Pediatrics, The Regional Neonatal Center, Maria Fareri Children's Hospital at Westchester Medical Center, Division of Newborn Medicine, New York Medical College, Valhalla, NY, USA.
Yanling Liao, Department of Pediatrics, New York Medical College, Valhalla, NY, USA.
Deepti Purohit, Department of Pediatrics, The Regional Neonatal Center, Maria Fareri Children's Hospital at Westchester Medical Center, Division of Newborn Medicine, New York Medical College, Valhalla, NY, USA.
Furong Hu, Department of Pediatrics, New York Medical College, Valhalla, NY, USA.
Davud Sulaymankhil, Department of Chemical Engineering, Cooper Union, NYC, NY, USA.
Sai Abhishek Narra, Cell Biology & Anatomy, New York Medical College, Valhalla, NY, USA.
Karen Hussein, Department of Pediatrics, The Regional Neonatal Center, Maria Fareri Children's Hospital at Westchester Medical Center, Division of Newborn Medicine, New York Medical College, Valhalla, NY, USA.
Selvakumar Subbian, Department of Medicine, Public Health Research Institute, New Jersey Medical School, Rutgers, The State University of Newark, NJ, USA.
Mitchell S. Cairo, Department of Pediatrics, New York Medical College, Valhalla, NY, USA.
Govindaiah Vinukonda, Department of Pediatrics, New York Medical College, Valhalla, NY, USA.
Edmund F. La Gamma, Department of Pediatrics, The Regional Neonatal Center, Maria Fareri Children's Hospital at Westchester Medical Center, Division of Newborn Medicine, New York Medical College, Valhalla, NY, USA.

Author Type(s)

Faculty

Journal Title

Stem Cells Translational Medicine

First Page

811

Last Page

824

Document Type

Article

Publication Date

12-18-2023

Department

Pediatrics

Abstract

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 TGFβ1, FGF2 expression. The early OL cell lineage by immunofluorescence and cell density quantitation showed significant reduction after IVH (P < .05 both PDGFR+, OLIG2+ at day 3); with significant recovery after injection of USSCs (P < .05 both PDGFR+, OLIG2+ at day 3). CSF protein and tissue mRNA levels of TGFβ1 were reduced by IVH and recovered after USSC (P < .05 for all changes). FGF2 showed an increased mRNA after USSC on day3 (P < .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.

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