7 - Protective Effect of BDNF-overexpressing Wharton's Jelly-derived Mesenchymal Stem Cells in Severe Intraventricular Hemorrhage in newborn rats

Monday, May 1, 2023

9:30 AM – 11:30 AM ET

Poster Number: 7
Publication Number: 7.433

so yeon jung, samsung medical center, seoul, Seoul-t'ukpyolsi, Republic of Korea; soyoon ahn, Samsung Medical Center, SEOUL, Seoul-t'ukpyolsi, Republic of Korea; young eun kim, Samsung Medical Center, seoul, Seoul-t'ukpyolsi, Republic of Korea; dong kyung sung, Samsung Medical Center, Seoul, Seoul-t'ukpyolsi, Republic of Korea; Misun Yang, Department of Pediatrics, Samsung Medical Center, Sungkyunkwan University School of Medicine, Gangnam-gu, Seoul-t'ukpyolsi, Republic of Korea; Se In Sung, Department of Pediatrics, Samsung Medical Center, Sungkyunkwan University School of Medicine, Gangnam-gu, Seoul-t'ukpyolsi, Republic of Korea; yunsil chang, Department of Pediatrics, Samsung Medical Center Sungkyunkwan University School of Medicine, seoul, Seoul-t'ukpyolsi, Republic of Korea

Presenting Author(s)

soyeon jung

researcher
samsung medical center
seoul, Seoul-t'ukpyolsi, Republic of Korea

Background:

Severe intraventricular hemorrhage (IVH) ensured brain injury and subsequent progression to post hemorrhagic hydrocephalus (PHH) increases mortality in extremely preterm infants. Mesenchymal stem cells (MSCs) transplantation has been studied as a possible therapeutic option. However, it is still necessary to develop methods to enhance the MSC’s therapeutic effect. As we previously proved that BDNF (brain-derived neurotrophic factor) is a pivotal factor in MSC’s neuroprotective effect.

Objective:

We aimed to investigate the therapeutic effect of BDNF-overexpressing human Wharton’s jelly (WJ) MSCs (BDNF-MSCs) in newborn rat model of IVH.

Design/Methods:

To induce severe IVH injury, 150μl of blood was injected into each bilateral ventricles of Sprague-Dawley rats on postnatal day (P) 4. Two days later, saline, naïve WJ-MSCs tagged with green fluorescent protein (GFP) (1< ![if !msEquation] > < ![endif] >10⁵/10μl) or WJ-MSCs overexpressing BDNF (1< ![if !msEquation] > < ![endif] >10⁵/10μl) were intraventricularly transplanted. At P35 when was behavioral test of passive avoidance test was performed, cerebrospinal fluid (CSF) and brain tissue were obtained for biochemical and histological analyses.

Results: Significantly increased number of TUNEL positive cells (as a marker for cell death) and ED1-positive cells (as a marker for activated microglia) were observed in IVH control rats. These increased cell death and inflammation were significantly attenuated in IVH rats received BDNF overexpressing MSCs (p-value< 0.05). Though IVH rats received naïve MSC showed a tendency to improve IVH induced increased cell death and inflammation, there was no statistical significance. IVH induced up-regulated CSF inflammatory cytokines including IL-1α, IL-1β, IL-6, and TNF-α were significantly decreased by BDNF overexpressing MSCs treatment (p-value< 0.05), but not by naïve MSC treatment. In the passive avoidance behavioral test, IVH induced impaired learning and memory function was significantly improved by naive-MSCs treatment (p-value< 0.05) and this protective effect was more enhanced by BDNF overexpressing MSCs treatment.

Conclusion(s):

BDNF overexpressing WJ-MSCs improves the therapeutic efficacy of naïve WJ-MSCs and attenuated brain injury including cell death, inflammation and memory functional impairment in newborn rat model of severe IVH.