Stem cell-based therapies for stroke in newborns

Review question

Can stem cell-based therapies save the lives or improve the long-term development of newborns who have a stroke?


Newborns sometimes develop stroke, which occurs when blood supply to part of the brain is blocked or when a blood vessel in the brain bursts. Babies with less severe stroke may make a full recovery or may have only mild intellectual problems. If the stroke is very big it can lead to death or to severe neurodevelopmental problems later in life. Some of these babies develop intellectual disabilities, behavioral problems, concentration difficulties, socialization problems, and cerebral palsy. Currently, there is no treatment for stroke.

What did we want to find out?

The aim of this Cochrane Review was to assess whether stem cell-based therapies could reduce death and improve the long-term development of newborns with stroke. We also wanted to know if this treatment had any unwanted effects. During stem cell-based therapy, stem cells are implanted into the baby (e.g. by injection) so that they can repair the brain cells that have been damaged by stroke. These stem cells may have come from humans or animals and may have been taken from cord blood, bone marrow, or other parts of the body.

What did we do?

We searched medical databases for clinical trials that looked at stem cell-based therapies for stroke in newborns.

Key results

We were unable to include any studies in our review. We identified three studies, but we excluded them all because they had an ineligible design or because they included newborns without stroke.

How current is the evidence?

The evidence is current to February 2023.

Authors' conclusions: 

No evidence is currently available to evaluate the benefits and harms of stem cell-based interventions for treatment of stroke in newborn infants. We identified no ongoing studies.

Future clinical trials should focus on standardizing the timing and method of cell delivery and cell processing to optimize the therapeutic potential of stem cell-based interventions and safety profiles. Phase 1 and large animal studies might provide the groundwork for future randomized trials. Outcome measures should include all-cause mortality, major neurodevelopmental disability and immune rejection, and any other serious adverse events.

Read the full abstract...

Perinatal stroke refers to a diverse but specific group of cerebrovascular diseases that occur between 20 weeks of fetal life and 28 days of postnatal life. Acute treatment options for perinatal stroke are limited supportive care, such as controlling hypoglycemia and seizures. Stem cell-based therapies offer a potential therapeutic approach to repair, restore, or regenerate injured brain tissue. Preclinical findings have culminated in ongoing human neonatal studies.


To evaluate the benefits and harms of stem cell-based interventions for the treatment of stroke in newborn infants compared to control (placebo or no treatment) or stem-cell based interventions of a different type or source.

Search strategy: 

We searched CENTRAL, PubMed, Embase, and three trials registries in February 2023. We planned to search the reference lists of included studies and relevant systematic reviews for studies not identified by the database searches.

Selection criteria: 

We attempted to include randomized controlled trials, quasi-randomized controlled trials, and cluster trials that evaluated any of the following comparisons.

• Stem cell-based interventions (any type) versus control (placebo or no treatment)
• Mesenchymal stem/stromal cells (MSCs) of a specific type (e.g. number of doses or passages) or source (e.g. autologous/allogeneic or bone marrow/cord) versus MSCs of another type or source
• Stem cell-based interventions (other than MSCs) of a specific type (e.g. mononuclear cells, oligodendrocyte progenitor cells, neural stem cells, hematopoietic stem cells, or induced pluripotent stem cell-derived cells) or source (e.g. autologous/allogeneic or bone marrow/cord) versus stem cell-based interventions (other than MSCs) of another type or source
• MSCs versus stem cell-based interventions other than MSCs

We planned to include all types of transplantation regardless of cell source (bone marrow, cord blood, Wharton's jelly, placenta, adipose tissue, peripheral blood), type of graft (autologous or allogeneic), and dose.

Data collection and analysis: 

We used standard Cochrane methods. Our primary outcomes were all-cause neonatal mortality, major neurodevelopmental disability, and immune rejection or any serious adverse event. Our secondary outcomes included all-cause mortality prior to first hospital discharge, seizures, adverse effects, and death or major neurodevelopmental disability at 18 to 24 months of age. We planned to use GRADE to assess the certainty of evidence for each outcome.

Main results: 

We identified no completed or ongoing randomized trials that met our inclusion criteria. We excluded three studies: two were phase 1 trials, and one included newborn infants with conditions other than stroke (i.e. cerebral ischemia and anemia).

Among the three excluded studies, we identified the first phase 1 trial on the use of stem cells for neonatal stroke. It reported that a single intranasal application of bone marrow-derived MSCs in term neonates with a diagnosis of perinatal arterial ischemic stroke (PAIS) was feasible and apparently not associated with severe adverse events. However, the trial included only 10 infants, and follow-up was limited to three months.