You are hereSeptember 5, 2018
Scaffolds Seeded With Molecule-Releasing Stem Cells Shows Promise In Treating Fatal Bone Disease
DURHAM, N.C. (SEPTEMBER, 2018)
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You are hereSeptember 5, 2018
Scaffolds Seeded With Molecule-Releasing Stem Cells Shows Promise In Treating Fatal Bone Disease
DURHAM, N.C. (SEPTEMBER, 2018)
A team of researchers developed a biocompatible scaffold seeded with molecule-releasing stem cells that, when implanted in mice with a rare but deadly bone disease called autosomal recessive osteopetrosis (ARO), showed potential to help these animals. The findings, recently published in STEM CELLS Translational Medicine (SCTM), might someday yield a treatment for humans afflicted by the same devastating condition.
One of every 250,000 babies born has ARO. ARO is caused by mutations in several genes involved in the formation, development and function of specialized cells called osteoclasts. Osteoclasts break down bone tissue during bone remodeling, a normal process in which old or damaged bone is removed and new bone is produced to replace it. In ARO the osteoclasts fail to resorb bone, leading to restriction of bone marrow cavity and cranial nerve spaces.
People with ARO have a high risk of bone fracture from minor bumps and falls or for no apparent reason. Abnormally dense skull bones pinch nerves in the patient’s head and face, often causing vision and hearing loss, facial paralysis or seizures. Anemia, slow growth, short stature and dental abnormalities are just some of the other symptoms. The condition leads to a high mortality rate in the child’s first years of life — mainly due to bone marrow failure and infection. A bone marrow transplant is the only treatment that has a favorable outcome for ARO patients — unless the ARO is due to lack of Receptor Activator of Nuclear Factor k B Ligand (RANKL), a molecule that is essential to the formation of osteoclasts and, thus, bone formation.
In the SCTM study, a research team led by Anna Villa, M.D., and Cristina Sobacchi, Ph.D., at the Italian National Research Council (CNR), Milan, evaluated how biomimetic scaffolds seeded with mesenchymal stromal cells (MSCs) that have been transduced with a viral vector producing soluble RANKL might help ARO patients lacking this molecule. (MSCs are isolated from bone marrow, adipose and other adult tissue sources, and have the capacity to differentiate into various cell types.)
“Defining a cure for RANKL-ARO is currently an unmet medical need whose solution is unfairly complicated, owing to the extreme rarity of these patients,” Dr. Sobacchi said. In collaboration with Prof. Anna Tampieri, at ISTEC-CNR, the team turned to biomimetic scaffolds because, she explained, “They are extremely versatile in terms of chemical composition and physical properties, which can be defined to accomplish specific applications. One property that can be added is the production/release of bioactive soluble factors, either directly from the biomaterial or from cells embedded within the biomaterial. We reasoned that pursuing this strategy would be appropriate to set up a cell-based therapy for RANKL-deficient ARO.”
The team tested their strategy on RANKL-/- mice, subcutane