Stem cells for hypoxic brain damage an innovative approach

Stem cells for hypoxic brain damage ? Could represent a potential new treatment for hypoxic ischemic encephalopathy (HIE)?

The applicability of umbilical cord blood stem cell therapy in children with acquired neurological disorders has seen a significant expansion in recent years.

The incidence of hypoxic ischemic encephalopathy (HIE) is 2.8 cases per 1,000 newborns with a postnatal death rate of 10-15% and 25-30% sequelae of neuropsychiatric disorders.

Finding new treatment to improve these outcomes is still a challenge in neonatology.

The results of a study evaluating a new approach have been completed at Duke University Hospital in the US  and published in The Journal of Pediatrics.

This first study was a small pilot clinical trial assessing the safety and feasibility of  umbilical cord blood stem cell infusion to newborns, with severe brain injury due to  shortage in brain oxygenation and /or blood supply previous, during or soon after the birth (hypoxic-ischemic encephalopathy).

Applying moderate hypothermia, as a therapy aiming to reduce the second stage brain damage has improved the outcome of these children. Therapy by reducing the body temperature of the newborn at 33 ° -34 ° C over a 72-hour period has been associated with a decrease in death rate and an improvement in neurological development at 2 years of age.

But still about 30% of cooled infants died or survived with impairment (cerebral palsy, epilepsy, mental retardation).

For them, the combination of hypothermia with a new treatment, targeting other mechanisms triggered by the brain injury or which could support the ongoing brain development, may bring the chance for a better outcome of these children.

Such a new therapeutic approach is the umbilical cord blood stem cell therapy. It was hypothesized that early infusion of newborn’s own cord blood may reduce the inflammatory process triggered by hypoxia and / or ischemia responsible for the brain lesions extension. (neuroprotection effect).

Underlying mechanisms responsible for the brain damage persist for hours or even days after the hypoxic event occur.

Besides reducing inflammation, stem cells by releasing cell growth factors may promote regeneration and restoration of affected nervous tissue (neuroregeneration effect). As a result,the therapeutic effect of stem cells would be expressed by diminishing the injured brain area and promoting its functional recovery.

The phase I clinical study has been conducted between January 2009 and June 2012.

23 children with severe brain hypoxia (severe HIE) received injections of their own stem cells from umbilical cord blood during the first 72 hours after birth.

One to four doses were administered. All of them have been followed for more than 1 year after infusion.

During the study 82 children with HIE didn’t have their own umbilical cord blood collected and therefore could be treated only by hypothermia applied in the intensive care unit.

In 2010, a new policy has been adopted in the hospital. According to this all pregnant who were considered “obstetric emergencies” had the possibility to choose for umbilical cord blood collection at birth of their child. For this purpose collection kits were placed in all delivery areas, operating suites, and the neonatology resuscitation equipment bag.

There were no significant side effects associated with umbilical cord blood stem cells infusion.

None of the children treated with stem cells died during hospitalization compared to the 11 children treated only by hypothermia at which the death rate was 13%.

One year after treatment, neurological evaluation could be performed for 18 children treated with cord blood stem cells infusion and 46 for children treated only by hypothermia.

74% of children treated with stem cells (13 children) and 41% of children treated by hypothermia only (19 children) showed a functional development score of over 85 on the Bayley scale.

This score evaluates the child's development from cognitive, language, motor, socio-emotional and adaptive point of view.

The result obtained in this first study needs to be complemented by a more complex study including a larger number of patients to have statistical relevance, but it is an encouraging first step for the use of cell therapy in these children.

Source:C. Michael Cotten & al.  "Feasibility of Autologous Cord Blood Cells for Infants with Hypoxic-Ischemic Encephalopathy" THE JOURNAL OF PEDIATRICS vol.164, No5.

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