Stem Cell Therapy for Neonatal Hypoxic-Ischemic Encephalopathy

Gonzales-Portillo, Gabriel S.; Reyes, Stephanny; Aguirre, Daniela; Pabon, Mibel; Borlongan, Cesar V.

doi:10.3389/fneur.2014.00147

Cited by 43 publications

(28 citation statements)

References 148 publications

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“…Therefore, a multifaceted therapeutic agent might be necessary to improve outcomes of patients with these intractable neonatal disorders. The pleiotropic beneficial effects of stem cell therapy, such as antiapoptotic, anti-inflammatory, antifibrotic, and antioxidative effects, have been observed in various animal models of BPD (5)(6)(7)(8)10), severe IVH (13-15), or HIE (11,25,26). Furthermore, in addition to their beneficial antiinflammatory effects, antibacterial activity of transplanted stem cells were observed in an animal model of Escherichia coli pneumonia (27).…”

Section: Pleiotropic Protective Effects Of Stem Cell Therapiesmentioning

confidence: 99%

Strategies to enhance paracrine potency of transplanted mesenchymal stem cells in intractable neonatal disorders

et al. 2017

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Mesenchymal stem cell (MSC) transplantation represents the next breakthrough in the treatment of currently intractable and devastating neonatal disorders with complex multifactorial etiologies, including bronchopulmonary dysplasia, hypoxic ischemic encephalopathy, and intraventricular hemorrhage. Absent engraftment and direct differentiation of transplanted MSCs, and the "hit-and-run" therapeutic effects of these MSCs suggest that their pleiotropic protection might be attributable to paracrine activity via the secretion of various biologic factors rather than to regenerative activity. The transplanted MSCs, therefore, exert their therapeutic effects not by acting as "stem cells," but rather by acting as "paracrine factors factory." The MSCs sense the microenvironment of the injury site and secrete various paracrine factors that serve several reparative functions, including antiapoptotic, anti-inflammatory, antioxidative, antifibrotic, and/or antibacterial effects in response to environmental cues to enhance regeneration of the damaged tissue. Therefore, the therapeutic efficacy of MSCs might be dependent on their paracrine potency. In this review, we focus on recent investigations that elucidate the specifically regulated paracrine mechanisms of MSCs by injury type and discuss potential strategies to enhance paracrine potency, and thus therapeutic efficacy, of transplanted MSCs, including determining the appropriate source and preconditioning strategy for MSCs and the route and timing of their administration.

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Section: Pleiotropic Protective Effects Of Stem Cell Therapiesmentioning

confidence: 99%

Strategies to enhance paracrine potency of transplanted mesenchymal stem cells in intractable neonatal disorders

et al. 2017

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“…Cell-based therapy studies have been conducted in small trials utilizing neural progenitor cells, umbilical cord mononuclear cells, and mesenchymal stem cells. These have been generally safe 33 and showed potential for limited improvement, although much more data are needed. Limited data exist for autologous cord blood therapy and autologous bone marrow mesenchymal cell therapy.…”

Section: New Therapeutic Resources and Researchmentioning

confidence: 99%

Report of a workshop on research gaps in the treatment of cerebral palsy

et al. 2016

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Cerebral palsy (CP) is heterogeneous in etiology and manifestations, making research into relevant therapies difficult and limiting the generalizability of the results. We report here on the NIH CP symposium, where stakeholders from academic, clinical, regulatory, and advocacy backgrounds discussed the major challenges and needs for moving forward with clinical research in CP, and outlined priorities and action items. New information is constantly generated through research into pathogenesis and etiology. Clinical research and new therapeutic approaches need to keep pace, through large data registry integration and new research designs. Development of standardized data collection, increasing academic focus on CP research, and iterative approaches to treatment throughout the patients' lives, have all been identified as areas of focus. The workshop identified critical gaps and areas of focus to increase the evidence base for therapeutic approaches to determine which treatments work best for which patients in the near future. These include consolidation and optimization of databases and registries, updates to the research methodology, and better integration of resources and stakeholders. DEFINING THE PROBLEM Cerebral palsy (CP) is a group of neurologic disorders of motor control with onset early in development and persistence throughout the lifespan. CP is the most common cause of motor disability in childhood, with an incidence of 2 to 3 per 1,000 live births, occurring 20 to 30 times more frequently in premature or low-birth-weight infants.1 These disturbances of movement and posture cause activity limitations.2 Those activity limitations resulting from spinal or neuromuscular disorders are excluded from the diagnosis. Various etiologies can cause the CP clinical spectrum but all have a disruption of motor control in common. In addition to prematurity, other known etiologies include developmental defects of the brain, perinatal stroke, hypoxia, shock, and fetal or neonatal inflammation/infection. However, CP may also occur in low-risk children for whom there is no obvious etiology or risk factor. CP is often accompanied by comorbidities such as seizures, communication deficits, hearing and vision deficits, and intellectual disability. There is a wide spectrum of functional outcomes from normal educational, career, and social activities to complete disability and dependence.An upper age limit for acquired pathology in the brain leading to CP is not absolute, but the onset of symptoms and the diagnosis are generally expected to occur by the age of 2. Given the heterogeneity in terms of etiology, pathology, clinical manifestations, and progression, it is best to consider CP as a collection of conditions rather than one uniform entity for developing treatment guidelines or conducting research on potential therapies.To address pressing research challenges, the National Institute of Neurological Disorders and Stroke (NINDS) organized a workshop with the main goal of discussing research needed to determine best ...

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“…Currently, WHO recommends DCC in HIV positive pregnant women: it is a quick and inexpensive method of enhancing haematologic status, preventing neonatal anaemia by enriching iron stores and ferritin levels and improving neurodevelopmental outcome. Moreover, a longer duration of placental transfusion allows an increase supply of valuable stem and progenitor cells, allows a better a fetal-to-neonatal transition and a greater red cell mass for oxygenation and iron content essential for the maturation of the preoligodendrocytes and myelin production [18,25,26].…”

Section: Discussionmentioning

confidence: 99%

Effects and safety of delayed versus early umbilical cord clamping in newborns of HIV-infected mothers

Pogliani

Erba

Nannini

et al. 2017

The Journal of Maternal-Fetal & Neonatal Medicine

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Objective: To investigate the effect of a 2 minutes-delayed cord clamp (DCC) versus early cord clamp (ECC) on neonate haemoglobin concentration 24 hours and 1 month after birth, and assess the safety of DCC concerning the risk of HIV infection. Design: Sixty-four mother-infant peers were enrolled. All mothers were on stable ARV therapy. Viral load, CD4 þ count and blood haemoglobin (Hb) concentrations 24 hours before delivery were collected from all mothers and their infants. Methods: All patients were enrolled at the Department of Paediatrics, AO FBF Sacco Hospital in Milan, and were followed until 18 months after birth. Women with haematological diseases and obstetrical complications were excluded. All of 64 mother and infants couples (32 ECC group and 32 DCC group) completed the study. ECC and DCC are defined as application of umbilical clamp within 30 seconds and 120 seconds after birth, respectively. Results: Mean birth weight was significantly higher in the DCC compared with ECC group. Mean Hb levels at birth were significantly higher in DCC than in ECC group (p ¼ .05): this difference persisted at 1 month of life. All newborns showed negative viral load. Conclusions: DCC 2 minutes after birth is proven to be a safe procedure, particularly beneficial in newborns from HIV mothers. The risk of anemia is significantly decreased at 24 hours after birth and persists at age of 1 month without any increased risk of neonatal jaundice or polycitemia. ARTICLE HISTORY

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Stem Cell Therapy for Neonatal Hypoxic-Ischemic Encephalopathy

Cited by 43 publications

References 148 publications

Strategies to enhance paracrine potency of transplanted mesenchymal stem cells in intractable neonatal disorders

Strategies to enhance paracrine potency of transplanted mesenchymal stem cells in intractable neonatal disorders

Report of a workshop on research gaps in the treatment of cerebral palsy

Effects and safety of delayed versus early umbilical cord clamping in newborns of HIV-infected mothers

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