Stem cell-based interventions for the prevention and treatment of intraventricular haemorrhage and encephalopathy of prematurity in preterm infants

Romantsik, Olga; Moreira, Alvaro; Thébaud, Bernard; Ådén, Ulrika; Ley, David; Bruschettini, Matteo

doi:10.1002/14651858.cd013201.pub3

Cited by 2 publications

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“…In summary, administration of a single dose of nh-UCBSCs in the subacute period after PIVH improved motor and behavioral function and decreased the severity of brain injury at adulthood in an ELGAN-equivalent neonatal rat model. A recent Cochrane review found no randomized controlled trials on benefits or harms of stem cell–based therapies for prevention or treatment of PIVH in preterm infants 53 . A phase I dose escalation trial of UCB-derived MSCs administered via the ICV route in ELGAN ( N = 9) with severe PIVH was not associated with increased mortality or serious adverse effects 54 .…”

Section: Discussionmentioning

confidence: 99%

“…A phase IIa trial of these cells versus normal saline in 23–34 week gestation preterm infants ( N = 22) with severe PIHV is currently active (NCT02890953). There are other ongoing clinical trials evaluating the efficacy and safety of UCBSCs for preterm brain injury, but not specifically for PIVH 53 . The results of our study provide the proof-of-concept for considering nh-UCBSCs in human infants with PIVH.…”

Section: Discussionmentioning

confidence: 99%

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Nonhematopoietic Umbilical Cord Blood Stem Cell Administration Improves Long-term Neurodevelopment After Periventricular-Intraventricular Hemorrhage in Neonatal Rats

et al. 2023

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Periventricular-intraventricular hemorrhage (PIVH) is common in extremely low gestational age neonates (ELGAN) and leads to motor and behavioral impairments. Currently there is no effective treatment for PIVH. Whether human nonhematopoietic umbilical cord blood-derived stem cell (nh-UCBSC) administration reduces the severity of brain injury and improves long-term motor and behavioral function was tested in an ELGAN-equivalent neonatal rat model of PIVH. In a collagenase-induced unilateral PIVH on postnatal day (P) 2 model, rat pups received a single dose of nh-UCBSCs at a dose of 1 × 106 cells i.p. on P6 (PIVH + UCBSC group) or were left untreated (Untreated PIVH group). Motor deficit was determined using forelimb placement, edge-push, and elevated body swing tests at 2 months ( N = 5–8). Behavior was evaluated using open field exploration and rearing tests at 4 months ( N =10–12). Cavity volume and hemispheric volume loss on the PIVH side were determined at 7 months ( N = 6–7). Outcomes were compared between the Untreated PIVH and PIVH + UCBSC groups and a Control group. Unilateral motor deficits were present in 60%–100% of rats in the Untreated PIVH group and 12.5% rats in the PIVH + UCBSC group ( P = 0.02). Untreated PIVH group exhibited a higher number of quadrant crossings in open field exploration, indicating low emotionality and poor habituation, and had a cavitary lesion and hemispheric volume loss on the PIVH side. Performance in open field exploration correlated with cavity volume ( r2 = 0.25; P < 0.05). Compared with the Untreated PIVH group, performance in open field exploration was better ( P = 0.0025) and hemispheric volume loss was lower (19.9 ± 4.4% vs 6.1 ± 2.6%, P = 0.018) in the PIVH + UCBSC group. These results suggest that a single dose of nh-UCBSCs administered in the subacute period after PIVH reduces the severity of injury and improves neurodevelopment in neonatal rats.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%