Human embryonic stem cell -- derived bone tissue closes massive skull injury

There are mice in Baltimore whose skulls were made whole again by bone tissue grown from human embryonic stem cells (hESCs).

Healing critical-size defects (defects that would not otherwise heal on their own) in intramembraneous bone, the flat bone type that forms the skull, is a vivid demonstration of new techniques devised by researchers at John Hopkins University to use hESCs for tissue regeneration.

Using mesenchymal precursor cells isolated from hESCs, the Hopkins team steered them into bone regeneration by using “scaffolds,” tiny, three-dimensional platforms made from biomaterials.

Physical context, it turns out, is a powerful influence on cell fate. Nathaniel S. Hwang, Jennifer Elisseeff, and colleagues at Hopkins demonstrated that by changing the scaffold materials, they could shift mesenchymal precursor cells into either of the body’s osteogenic pathways: intramembraneous, which makes skull, jaw, and clavicle bone; or endochondral, which builds the “long” bones and involves initial formation of cartilage, which is then transformed into bone by mineralization.

Mesenchymal precursor cells grown on an all-polymer, biodegradable scaffold followed the endochondral lineage. Those grown on a composite scaffold made of biodegradable polymers and a hard, gritty mineral called hydroxyapatite went to the intramembraneous side.

Biomaterial scaffolds provide a three-dimensional framework on which cells can proliferate and differentiate, secrete extracellular matrix, and form functional tissues, says Hwang. In addition, their known composition allowed the researchers to characterize the extracellular microenvironmental cues that drive the lineage specification.

The promise of pluripotent embryonic stem cells for regenerative medicine hangs on the development of such control techniques. Left to themselves, hESCs in culture differentiate wildly, forming a highly mixed population of cell types, which is of little use for cell-based therapy or for studying particular lineages.

Conventional hESC differentiation protocols rely on growth factors, co-culture, or genetic manipulation, say the researchers. The scaffolds offer a much more efficient method.

As a proof of principle, Hwang and colleagues seeded hESC-derived mesenchymal cells onto hydroxyapatite-composite scaffolds and used the resulting intramembraneous bone cells to successfully heal large skull defects in mice. The Hopkins researchers believe that this is the first study to demonstrate a potential application of hESC-derived mesenchymal cells in a musculoskeletal tissue regeneration application.

Source: American Society for Cell Biology

Related stories:

New Stanford diagnostic test for rare leukemia appears to give faster results, study finds
A new twist on a well-known cell sorting technique may allow physicians to diagnose rare leukemias in hours instead of weeks, according to a study by researchers at the Stanford University School of Medicine and UC-San Francisco. The clinical promise of the Stanford-developed approach, which eavesdrops on individual cells to decipher potentially dangerous molecular conversations, is likely to extend to many other disorders in which cell-signaling pathways are disrupted.
Scientists develop new, more sensitive nanotechnology test for chemical DNA modifications
Researchers at The Johns Hopkins University School of Medicine in Baltimore have developed a novel test to screen for chemical modifications to DNA known as methylation. The technology potentially could be used both for early cancer diagnoses and for assessing patients' response to cancer therapies.
Resetting immune system in bid to beat scleroderma
(AP) -- First Bari Martz's fingers turned blue. Then she started gasping for breath, and her joints stiffened so that she couldn't even open her hands. Doctors diagnosed scleroderma, part of an insidious family of diseases where the immune system attacks a patient's own body, sometimes enough to kill.
New leukemia signal could point way to better treatment
Cancer researchers at the Stanford University School of Medicine have discovered a promising new chemotherapy target for a deadly form of leukemia. Their discovery hinges on a novel "double agent" role for a molecular signal that regulates cell growth.
Engineered stem cells carry promising ALS therapy
(PhysOrg.com) -- Using adult stem cells from bone marrow as "Trojan horses"to deliver a nurturing growth factor to atrophied muscles, Wisconsin scientists have successfully slowed the progression of ALS in rats.
New synthetic form of protein holds promise to stop cancer spread
Researchers at the Medical College of Wisconsin in Milwaukee have a pending patent on a new synthetic form of a protein involved in certain types of cancers and immune system diseases.
Embryonic stem cells might help reduce transplantation rejection
Researchers have shown that immune-defense cells influenced by embryonic stem cell-derived cells can help prevent the rejection of hearts transplanted into mice, all without the use of immunosuppressive drugs.
Genetic variants associated with vitamin B12
Researchers at the Harvard School of Public Health (HSPH) and their collaborators at Tufts University and the National Cancer Institute (NCI) have identified a common genetic influence on B12 vitamin levels in the blood, suggesting a new way to approach the biological connections between an important biochemical variable and deficiency-related diseases.

News discussion:

General Science news