WINSTON-SALEM, N.C. – May 30,
2018 – Wake Forest Institute for Regenerative Medicine (WFIRM) scientists
have developed a 3-D brain organoid that could have potential applications in
drug discovery and disease modeling. This is the first engineered tissue
equivalent to closely resemble normal human brain anatomy, containing all six
major cell types found in normal organs including, neurons and immune cells.
In a study published this month in
Scientific Reports, the researchers report that their advanced 3-D organoids
promote the formation of a fully cell-based, natural and functional barrier -
the blood brain barrier - that mimics normal human anatomy.
The blood brain barrier is a
semipermeable membrane that separates the circulating blood from the brain,
protecting it from foreign substances that could cause injury. This development
is important because the model can help to further understanding of disease
mechanisms at the blood brain barrier, the passage of drugs through the
barrier, and the effects of drugs once they cross the barrier.
“The shortage of effective
therapies and low success rate of investigational drugs are due in part because
we do not have a human-like tissue models for testing,” said senior author
Anthony Atala, M.D., director of WFIRM. “The development of tissue engineered
3D brain tissue equivalents such as these can help advance the science toward
better treatments and improve patients’ lives.”
The development of the model opens
the door to speedier drug discovery and screening, both for neurological
conditions and for diseases like HIV where pathogens hide in the brain and
avoid current treatments that cannot cross the blood brain barrier. It may also
allow for disease modeling of neurological conditions such as Alzheimer’s
disease, multiple sclerosis and Parkinson’s disease so that researchers can
better understand their pathways and progression.
Thus far the researchers have used
the brain organoids to mimic strokes in order to measure impairment of the
blood brain barrier and have successfully tested the model’s permeability with
large and small molecules.
“Using an engineered tissue model
provides a platform that can be used to understand the fundamental principles
at play with the blood brain barrier and its function, as well as the effects
of chemical substances that cross it,” said Goodwell Nzou, a Ph.D. candidate at
WFIRM who co-authored the paper.
Co-authors include: John Jackson,
Ph.D., and Sean Murphy, Ph.D., WFIRM faculty; Elizabeth Wicks, Stephanie Seale,
C.H. Sane, A. Chen, all students who participated in the Summer Scholars
program; and Robert Wicks, M.D., Wake Forest Baptist, Neurological Surgery.
The authors declare no competing
interests and there was no external funding.