Bone tissue generation: A truly marrowing Summer

This Summer, I was lucky enough to be asked to be part of a research team at Glasgow University, looking into an alternative and less invasive source of bone grafts.

As is well known, spinal injuries and conditions related to aging are becoming a huge problem in today’s society, with the steep rise of life expectancy in the last few decades. The main solution to treat such injuries is a bone graft, but often, grafts can be seen as invasive and painful. It is also known that the bone growth factor used here (BMP2) has some unpleasant medical side-effects. These include possible tumour growth and unnecessary pain – both things definitely worth avoiding [1]

To combat this issue, researchers at Glasgow University have started investigating the newly discovered technique of “nano-kicking”. [2], which looks set to be a potentially reliable source of bone tissue. This technique makes use of a bioreactor, mesenchymal stem cells and osteogenesis (this being the process of bone generation). Together, these aim to form new bone tissue from the patients’ own stem cells.

 

How is bone tissue is formed?

Bone tissue forms by a process called osteogenesis. This is whereby osteoblasts cells initiate two processes – intramembranous and endochondral ossification. Intramembranous ossification is the initial laying down of bone tissue. Endochondral ossification is the cartilage model used for the healing of fractures. The osteoblasts being used are derived from osteoprogenitor cells, found in the bone marrow. These processes are visualised in the info-graphics below.

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Figure 1. Intramembranous ossification. (Image 1)

 

endochondral

Figure 2. Endochondral ossification. (Image 2)

Nano-kicking, mechanotransduction and tissue engineering

The bioreactor developed makes use of nano-kicking to grow bone tissue. Put simply, “nano-kicking” is a technique that makes use of vibrations within a bioreactor. It causes given cells to vibrate at 1000 times a second, “kicking” them and causing mechanotranduction. This process then leads to bone formation.  The advantage of the reactor is that it’s a safe and sterile environment, and frequencies can be changed as needed.

Mechanotransduction is a process that allows the formation of bone (3) , and is composed of four stages: Mechanotransduction, mechanocoupling, biochemical coupling, transmission from the sensor and the response from the effector. This process is seen as essential in the human body, as it is how cells turn physical forces in to biochemical responses. It is the essential bridge between the bare bones of it all and the finished product. It is helped greatly, or some would say even made possible, by integrins. These allow for forces to be transmitted and cell functions to be regulated.

The technique itself used inside the bioreactor is tissue engineering. This is widely used in biology, and is the use of extra-cellular matrix guides to see the growth and regulation of tissues. It involves the use of many nano-scale cues, to ensure only the cells intended are cultured.

 

Possible applications of the work carried out

All of this is happening in the Joseph Black lab, in Glasgow. Just now only small amounts of bone tissue have been able to be grown successfully with the technique. (the image below shows the bioreactor in use)

bioreactor-group-media-16th-17th

Figure 3. Newly developed bioreactor in use with six and twelve well plates.

An interesting aside, thought of by researchers at the Joseph Black lab, is that nano-kicking could slow tumour growth and encourage healthy bone growth [4].  The eventual aim is for large sections of bone to tissue engineered. If this is successful, then it could even be a treatment for osteoporosis and spinal fractures. Care of those with osteoporosis in the US is thought to cost around $5,000,000,000 a year – [5] so any move that could reduce this cost will be welcomed with open arms. Glasgow University and Southern General Hospital teams also hope to improve “whole body therapy” with this technique, and in turn improve patient recovery times.

Of course, most of these treatments and ideas are hypothetical. However, with more research in this area they stand a good chance of becoming a reality.

References:

(1) – Rui, Y. F., Lui, P. P. Y., Ni, M., Chan, L. S., Lee, Y. W., & Chan, K. M. (2011). Mechanical loading increased BMP-2 expression which promoted osteogenic differentiation of tendon-derived stem cells. Journal of Orthopaedic Research, 29(3), 390–396. http://doi.org/10.1002/jor.21218

(2) – http://www.gla.ac.uk/news/archiveofnews/2013/april/headline_274263_en.html

(3) – Huang, H., Kamm, R. D., & Lee, R. T. (2004). Cell mechanics and mechanotransduction: pathways, probes, and physiology. American Journal of Physiology. Cell Physiology, 287(1), C1–11. http://doi.org/10.1152/ajpcell.00559.2003

(4) – https://www.researchgate.net/project/Manipulation-of-cancer-cells-by-nanokicking-strategies-to-control-migration-proliferation-and-apoptosis?_esc=profileProjectCards&_sg=ihe7t_lICRPuRdDR5IKERttaob1N9TGITC5nwMKT7Z-XhFIkEqrcX6jCgvFocjAN4722Wmo0Hc6dl5vsFHZ3ug

(5) – Rowley, D., & Clift, B. (1994). Prevention of injuries. In Skeletal trauma in old age (1st ed., p. 6). London: Chapman and Hall.

Image credits

(Image 1) – http://www.medbullets.com/step1-msk/12021/bone-formation

(Image 2) – https://www.blogger.com/blogin.g?blogspotURL=http://montejanoctlea.blogspot.co.uk/

(Feature Image) – http://kiraknoop.wixsite.com/connectivetissue/bone

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