Tuesday, 7 May 2013

Researchers create personalised bone grafts from induced pluripotent stem cells

Yesterday, researchers from the New York Stem Cell Foundation (NYSCF) reported that they have created personalised bone substitutes which can be used to treat large, bone defects. The grafts come with no risk of rejection and can cover the exact needs of any patient, say the researchers.

To create the 3-dimensional bone grafts, the researchers first harvest skin cells and use special factors to turn them into induced pluripotent stem cells, which in turn are guided into becoming bone-forming progenitor cells. Next, the progenitors are seeded onto a scaffold which is a placed in a special device, called a bioreactor. The bioreactor mimics the natural developmental environment and provides nutrients, removes waste products, and stimulates bone formation.

"Bone is more than a hard mineral composite, it is an active organ that constantly remodels. Blood vessels shuttle important nutrients to healthy cells and remove waste; nerves provide connection to the brain; and, bone marrow cells form new blood and immune cells.” said Darja Marolt, one of the two leading researchers. 

Cross-section of a long bone showing both spongy and compact osseous tissue

In the corresponding press release, the researchers mention that in the past many researchers have used other cell sources to create bone grafts. For example, mesenchymal stem cells (MSCs) can be used to form both bone and cartilage, however they fail to form the underlying vasculature and nerve tissues. Another option is to use embryonic stem cells, however the resulting bone tissue may provoke an immune rejection response once transplanted. This is why the NYSCF scientists decided to give iPSCs a try.

“No other research group has published work on creating fully-viable, functional, three dimensional bone substitutes from human iPS cells. These results bring us closer to achieving our ultimate goal, to develop the most promising treatments for patients.” said Giuseppe Maria de Peppo, the other leading researcher.

During the study, the researchers first created three human induced pluripotent stem cell lines (hiPSCs), each from a different tissue and reprogramming background. The hiPSCs were then triggered into becoming MSCs and were seeded into osteoconductive scaffolds in perfusion bioreactors. The biggest fear when using iPSCs is that they may start forming tumours. For this reason, the researchers transplanted the grafts under the skin of immuno-compromised mice. Twelve weeks later, the grafts had started maturing into bone tissue and a few blood vessels from the host had integrated with the transplanted tissue.

The study's results pave the way for growing patient-specific bone substitutes for reconstructive treatments of the skeletal system and for constructing qualified experimental models of development and disease, say the researchers.

“Following from these findings, we will be able to create tailored bone grafts, on demand, for patients without any immune rejection issues. This is not a good approach, it is the best approach to repair devastating damage or defects.” said Susan L. Solomon, CEO of NYSCF. 

Although the scientists describe their study as a "major advance" in the field of bone regeneration, they still warn that more research is needed to assess the safety and efficacy of the iPSCs bone grafts before trying them on human patients.

Giuseppe Maria de Peppoa, Iván Marcos-Camposb, David John Kahlera, Dana Alsalmana, Linshan Shanga, Gordana Vunjak-Novakovicb, & Darja Marolta (2013). Engineering bone tissue substitutes from human induced pluripotent stem cells Proceedings of the National Academy of Sciences

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