Use of stem cells in perinatal asphyxia: from bench to bedside

Abstract

Objectives: To present recent scientific evidence on the effects of stem cell transplantation in animal models of neonatal hypoxic-ischemic brain injury and address the translational relevance of cell therapy for clinical application in this context. Sources:The PubMed and Scopus databases were used to select articles. The selection criterion was the specificity of articles regarding the subject studied, preferably articles published from 2000 onward. We also reviewed classic articles from previous years that were applicable to this review. Summary of the findings:Stem cells from different exogenous sources may exhibit neuroprotective properties in experimental models of neonatal hypoxia-ischemia. In most animal experiments, the morphological and functional benefits observed were independent of neural differentiation, suggesting associated mechanisms of action, such as the release of trophic factors and inflammatory modulation. Conclusions:Based on the experimental studies analyzed, cell therapy may become a promising therapeutic approach in the treatment of children with hypoxic-ischemic encephalopathy. However, further studies are warranted to elucidate potential mechanisms of action of these cells and to define safe and effective clinical strategies.J Pediatr (Rio J). 2010;86(6):451-464: Hypoxic-ischemic encephalopathy, stem cells, asphyxia, cell therapy. ResumoObjetivos: Apresentar evidências científicas recentes sobre os efeitos do transplante com células-tronco em modelos animais de lesão cerebral hipóxico-isquêmica neonatal e abordar os aspectos translacionais relevantes à aplicação clínica da terapia celular nesse contexto. Fonte dos dados:Para a seleção dos artigos, utilizou-se a base de dados PubMed e Scopus. O critério de seleção de artigos foi a especificidade em relação ao tema estudado, preferencialmente a partir do ano de 2000. Também foram revisados artigos clássicos de anos anteriores que se aplicavam ao propósito desta revisão. Síntese dos dados:Células-tronco de diferentes fontes exógenas podem exibir propriedades neuroprotetoras em modelos experimentais de hipóxia-isquemia neonatal. Na maioria dos experimentos animais, os benefícios morfológicos e funcionais observados foram independentes da diferenciação neural, sugerindo mecanismos de ação associados, tais como a liberação de fatores tróficos e a modulação inflamatória. Conclusões:Baseado nos estudos experimentais analisados, a terapia celular pode tornar-se uma promissora abordagem terapêutica no tratamento de crianças com encefalopatia hipóxico-isquêmica. No entanto, estudos adicionais necessitam ser realizados a fim de elucidar os possíveis mecanismos de ação dessas células e definir estratégias clínicas seguras e efetivas.J Pediatr (Rio J). 2010;86(6):451-464: Encefalopatia hipóxico-isquêmica, células-tronco, asfixia, terapia celular.

Treatment advances in neonatal neuroprotection and neurointensive care

“…151,152 Animal studies support the idea that cord blood and mesenchymal stem cells, cell types that are available in a clinical setting, have a neuroprotective effect in neonatal HIE. 153 These effects have been attributed to immunomodulation, activation of endogenous stem cells, release of growth factors, and antiapoptosis mechanisms.…”

Rescuing the neonatal brain from hypoxic injury with autologous cord blood

“…Owing to the poor survival of the transplanted cells and little evidence for neural differentiation, bystander effects have been postulated to be the main mechanisms for functional recovery after CB transplantation, including release of neurotrophic factors to stimulate endogenous neurogenesis, prevention of cell loss and immunomodulation (Figure 4). 17,97,98 It has also been suggested that stem cell engraftment in the brain may not be critical for functional recovery provided that neurotrophic factors secreted by exogenous cells could reach the ischemic brain. 93 However, in most of the animal studies, human CB cells were injected without prior or concomitant immunosuppression.…”

The Role of Extracellular Vesicles in the Developing Brain: Current Perspective and Promising Source of Biomarkers and Therapy for Perinatal Brain Injury

“…Stem cells, which are self-renewing and considered the most primordial and least committed cells offer significant promise for treating perinatal brain injury (Kennea and Mehmet, 2004;Santner-Nanan et al, 2005;Vawda et al, 2007;Ikeda, 2008;de Paula et al, 2010; given their anti-inflammatory (Li et al, 2005;Murphy et al, 2010;Kim et al, 2012), trophic (van Velthoven et al, 2012Fu et al, 2017), and regenerative (Ilancheran et al, 2007;van Velthoven et al, 2010;Donega et al, 2014) capabilities. Indeed, neonatal models of hypoxic brain injury using different stem cell types support their therapeutic utility (van Velthoven et al, 2010(van Velthoven et al, , 2012Kim et al, 2012;Donega et al, 2014) and presently there are several adult stroke clinical trials underway (e.g., clinical trials registry numbers: NCT02605707, NCT01151124, NCT04434768, NCT02980354).…”