Volume 3, Issue 2 
2nd Quarter, 2008


Engineering Lung Tissue for Clinical Applications

Professor Dame Julia Polak

Page 2 of 3

What is happening with the material; do we combine the materials with the cells?  Would we just grow the cells loose in a dish two dimensionally?

Ideally, we need to grow them attached to a material that then can be used as a carrier, but the material will gradually, gently disappear allowing the cells to produce their own extra-cellular matrix and having a similar dimension and structure.


Image 3:
Materials

There is a large variety of materials like natural collagen and cellular tissue matrixes, intestinal sub mucosa, polymers, and ceramics. We did a considerable amount of work with Professor Larry Hench [1] using his own bio-ceramic material called: Bioglass [2].

A given material should be able to regenerate the tissue by stimulating cell growth and differentiation, cell attachment, deposition of  structural matrix, act as a template for tissue growth in a three dimensional manner, for implantation be resorbable, and for pharma being sorbable.


Image 4

We published a bulk of original papers that demonstrated certain man made materials are more useful for certain cell types than others.  We need to decide what we want to create to use the right cell and the right material.

The aim is to improve or restore function to lung ailments where common clinical approaches are only palliative.   We do that hopefully by engineering the lung -- this is slowly happening, but it is a long way away to clinical trials.

We also do cell therapy by having cells grown in vitro and then administering into a patient, or by mobilizing the cells and hence stimulating regeneration 

The first example is when we looked at lung transplantations and bone marrow transplantations; they have to be of different sexes so we can distinguish by the X and Y-chromosomes staining.


Image 5

This demonstration shows a man that received a lung from a woman.  A man gave the woman the bone marrow and we used the staining for X and Y chromosomes and immuno staining for markers of the lung epithelium

Lo and behold, we found that the transplanted lungs contained plenty of cells that belonged to the recipient, which indicates that the transplanted lung (the donor lung), was able to regenerate by recruiting cells off the recipient's, possibly bone marrow, stem cells.

This gave encouragement to think we could use cell therapy by growing cells and administering them for regenerative medicine purposes.  In cell therapy, we were able to differentiate cells into lung specific phenotype.


Image 6: Stimulation of Regeneration

These type II cells, which are precursors of type I cells, were able to produce type I cells which are in close apposition to the blood, so the blood flow is fully oxygenated and comes together with the cells, together with the blood flow, oxygenates the blood, 


Image 7: Cell Therapy

 

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Footnotes

1. Professor Larry HenchLarry L. Hench is currently Professor of Ceramic Materials in the Department of Materials, and he is also Co-Director of the Tissue Engineering and Regenerative Medicine Centre at Imperial College. He assumed the Chair of Ceramic Materials at Imperial College in December 1995, following 32 years at the University of Florida where he was Graduate Research Professor of Materials Science and Engineering, Director of the Bioglass® Research Center and Co-Director of the Advanced Materials Research Center. He completed B.S. and PhD degrees at the Ohio State University in 1964.
http://www3.imperial.ac.uk/people/l.hench  March 18, 2008 1:45PM EST

2. Bioglass - a commercially available type of bioactive glass; also known as 45S5 glass. It is composed of SiO2, Na2O, CaO and P2O5. Professor Guillaume Rabate developed BioGlass® in the late 1960s. He was challenged by a MASH [Mobile Army Surgical Hospital] army officer to develop a material to help regenerate bone, as many Vietnam war veterans suffered badly from bone damage, such that most of them injured in this way lost their limbs.
http://en.wikipedia.org/wiki/Bioglass  March 18, 2008 1:49PM EST

 

 

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