Regenerative medicine has yet to designate biomarkers that can identify patients likely to respond to a stem cell therapy based on their expression of a clinical or molecular profile congruent with the therapeutic mechanism-of-action (MOA) of the stem cell for that condition, while withholding treatment from likely non-responders.
Richard E. Hartman, et al. addressed that challenge by approaching a prototypical condition for which stem cell transplantation has been proposed: perinatal/neonatal cerebral hypoxic-ischemic injury (HII) (also termed “asphyxia”), a form of stroke.
It occurs in 2 to 4 newborns per 1000. Despite the use of therapeutic hypothermia, 80% of asphyxiated newborns develop neurologic signs, with 10-20% remaining significantly impaired (e.g., cerebral palsy, mental and motor disability, epilepsy).
Richard E. Hartman, et al., have demonstrated how magnetic resonance imaging (MRI) can be applied to predict the efficacy of using human neural stem cells to treat a brain injury, which could be used as a biomarker to help improve the efficacy of stem cell therapies.
A Tool to Predict a Successful Treatment
There are many ongoing trials for conditions such as Parkinson’s disease, spinal cord injury, and other neurological conditions. That is why creating tools to predict the efficacy of neural stem cell therapy could improve the success of those trials.
The team used MRI to measure the main areas surrounding regions of hypoxic-ischemic injury in rats, one of which is the penumbra, a region of mildly injured or stunned neurons, and the core, which consists of dead neurons.
They found that rats with a larger penumbra and smaller core that received human neural stem cells had better neurological outcomes, including improved memory, demonstrated by the ability to swim to a hidden platform (Morris Water Maze test), and a greater willingness to venture into a brightly lit area (open field test).
In these rats, the penumbra — to which the neural stem cells homed avidly — became normal tissue (based on MRI and histological standards), while the core remained unimproved and attracted few cells. Penumbra that did not receive cells became part of the core, populated by dead neurons — indicating the benefit of the stem cell treatment.
Evan Y. Snyder, professor and director of the Center for Stem Cells and Regenerative Medicine at Sanford Burnham Prebys said in an interview:
“This approach to brain lesion classification is a powerful patient stratification tool that allows us to identify newborns who may benefit from this stem cell therapy, and protect others from undergoing unnecessary treatment.” Based on their findings, only newborns with a large penumbra volume in relation to core volume should receive a transplant of human neural stem cells. And also, newborns so severely injured that only a core is present, or babies with such a mild case of HII that not even a penumbra is present, should not receive human neural stem cells, as the treatment is unlikely to be impactful.
Richard E. Hartman, et al. A Biomarker for Predicting Responsiveness to Stem Cell Therapy Based on Mechanism-of-Action: Evidence from Cerebral Injury. Cell Reports, 2020; 31 (6): 107622 DOI: 10.1016/j.celrep.2020.107622
Sanford Burnham Prebys Medical Discovery Institute. “Scientists show MRI predicts the efficacy of a stem cell therapy for brain injury: First ‘biomarker’ for regenerative medicine may help researchers identify the people most likely to benefit from stem cell treatment.” ScienceDaily. ScienceDaily, 12 May 2020.