New protocol could signal shift

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Researchers created this new method at the University of Sydney, Australian Research Center (ARC) for Innovative BioEngineering. This can result in a change on the way bone is treated by stem cell therapy.

Defects inside bone, that are large sized, and loss from cancer “or trauma” may lead to scar tissue, that affects the bones’ ability to fix and regrow itself. Auto grafting, which is the gold standard as of right now, has disadvantages, which include the following: limited donors available, and donor location morbidity.

Researchers are left thinking of ways to work with bone cells, making bone tissue engineering an emerging field that has promising potential in the long run.

Induced Pluripotent Stem Cells

Zufu Lu, Ph. D., researcher for University of Sydney’s Bio materials and Tissue Engineering Researcher Unit and ARC, talked about progress for the induced pluripotent stem cell ( iPSC ) technology. It could eventually train fibroblasts to progenitor cells from different stages of development and give exciting direction for tissue fixing and regrowth. Lu co-leads the SCTM study as investigator, along with Professor Hala Zreigat, Ph. D, leader and director of ARC.

Progenitor cells

Lu added that iPSC technology demonstrates the ability to source unlimited supply of progenitor cells, and lets patients use their own cells for the use of tissue fixing and regrowth, which shows little to no immunity rejection. However this kind of technology has several drawbacks. These drawbacks include, mandatory challenging training through Yamanaka factors (Oct3/4, Sox2, Klf4, c-Myc).

Adding to the challenges, certain stimuli are needed to lead iPSCs to become progenitor cells based on developmental stage. Lu also states that leftover iPSCs can show appearance of tumors after implantation.


One loophole to go around this problem by recent studies, is by direct training the fibroblasts to bone cells. According to Profesor Zreigat, fibroblasts are similar to osteoblasts. Similar transcription records show that they can form hypothesis on unique factors made by osteoblasts, which have capability to getting fibroblasts to transform into cells with osteoblast-like characteristics.

Natural Factors and Fibroblasts

Earlier studies showed that fibroblasts made many cell types that depended on genetic manipulating using one or more transcription regulators. Like iPSCs, training fibroblasts in this approach shows built in technical and safety problems. The research team led by Lu and Zreigat, think that a method using natural factors can lead to better control on training and enhancing safety.

Dr. Lu stated that “chemical induction of cell training is different from genetic reprogramming, in that it is pretty fast and changeable, making it more susceptible to changes, in being able to control factor dosage and / or combinations with other molecules.”


At the beginning, the research team saw that media trained by osteoblasts from humans can lead to training fibroblasts from humans to working osteoblasts. Professor Zreigat goes on saying that proteomic analysis showed single organic bio active protein, insulin growth factor binding protein-7 (IGFBP7), showing big increase with media trained by osteoblasts, versus media being conditioned by fibroblasts.

Protein-7 (IGFBP7)

In fact, this showed researchers to test IGFBP7’s capability as a transcription factor. They found that it successfully led to a change from fibroblasts and osteoblasts in vitro. Then they tested a mouse model, and saw favorable results when fibroblasts made tissue that mineralized itself. This change had to do with senescence and relying on autocrine IL-6 signaling.

Dr. Lu, and Professor Zreigat both stated that their approach they elaborated on shows great improvements over conventional approaches, such as iPSCs and adult mesenchymal stem cells.


Anthony Atala, M.D., Editor-in-Chief of STEM CELLS Translational Medicine and director of Wake Forest Institute of Regenerative Medicine, states that bone tissue engineering is an emerging area of study, which can allow cell therapies to have a lot of translational future, but cell-based approaches as of now show drawbacks.

This particular study was done at Charles Perkins Center and Children’s Hospital, located in Westmead, University of Sydney.

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