Volume 3, Issue 2 
2nd Quarter, 2008


Engineering Lung Tissue for Clinical Applications

Professor Dame Julia Polak

Page 3 of 3

What do we do towards clinical applications?  We have an ongoing research with another German company called Novalung.  They have produced polymers, and these polymers are hollow polymers.  They allow the blood to penetrate and to oxygenate it ex vivo.  Then blood comes back into the patient oxygenated, and the patient can wait for the transplant, or maybe recover if there was an acute lung injury.

The question then arose:  Could we attach type II lung cells to this particular polymer, and then enhance the polymeric oxygenation that is already helping the patients, but may help even more?  This is what we are currently trying out at Imperial College with cells and polymers, and to see if that will help to save the lungs.


Image 8

We also have a program for lung repair. You see the model of chronic obstructive pulmonary disease of a smoker's lungs.   This can be done by enhancing the proliferation of resident stem cells, or using bone marrow stem cells, and the lung-assist device with the cells that I referred to before, or using eventually three- dimensional constructs.


Image 9

For the time being, we have chosen to use umbilical cord stem cells.  These umbilical cords are ethically easy, a hundred million births globally each year, and an excess of ten million liters of human umbilical cord blood. Over fifty thousand kilometers of umbilical cord can be produced, and the vast majority is discarded.

We wanted to see whether we could put these clinically ready and available umbilical cord cells into the alveolar space of patients with Emphysema or Chronic Obstructive Pulmonary Disease.

We are combining efforts with a company in Israel called Gamida.  They have clinical grade umbilical cord cells, and we are doing the animal experiments for proof of concept to be followed by Phase 1 clinical trials.

The problem is (and the whole world has the problem), how do we produce sufficient numbers of cells for a diverse set of people's need?  We would really need to have quantities of identical cells reproducible.

We are not going to give patient A one group of cells and patient B, different cells.  We really need to have a sufficient number of identical cells.


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What we are developing here is Bio-processing Engineering at Imperial College. This is a typical bioreactor that rotates and perfuses.  We want to achieve control, reproducibility, validation, and safety. This is a dynamic, three-dimensional perfused culture system where we only add the growth factors and then we non-invasively check how the cells are behaving, and this is an illustration.


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What we did is we encapsulated the cells in beads.  The beads are FDA approved, gelatin beads, and the cells can be grown there, and then they can be cultured in a fine medium.
We also encapsulated human stem cells in alginate bead and left them there for almost 130 days.  Then took them out and differentiated into a lung cells, and the cells were alive

As the sensors are telling us what factors we should add, we can maintain the cells in good, healthy condition.  


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I believe we are getting close to initial clinical trials.  You must have all heard of clinical trials for heart repair, or for retinal and eye repair, or cartilage and skin repair.  

I think we need to have the basic science running in parallel to understand the principles and the properties of cell therapy and tissue engineering alongside the preparation for clinical trials by doing the proof of concept into acceptable small and large animal models.

Therefore, there are apparently separate fields of the stem cells that we are dedicated to working to understand development, or the tissue engineering that started from materials by replacing identical growth tissues in others.

The gene therapy field, the nanotechnology field, and the regenerative medicine field are all converging to help toward clinical application; to help clinical conditions where the situation is irrevocable. In the future, I believe we are likely to rewrite the books of medicine.


Footnotes

1. Novalung – A Hechingen, Germany based company whose mission is: the development and introduction of new enabling devices for advanced protective ventilation. Mechanical ventilation has helped create the discipline of critical care and improve outcomes.
http://www.novalung.com/eng/company.asp  March 10, 2008 3:39PM EST

2. Alveolar cells - cells lining the alveoli of the lung.
The American Heritage STEDMAN’S Medical Dictionary. Boston, New York: Houghton Mifflin Company, 2004: 33.

3. Gamida Cell – is developing cell therapies based on expanded stem cells for the treatment of such illnesses as blood cancers, cardiac disease and neurological disorders. The Company is dedicated to making a significant difference in the clinical practice of modern medicine by first creating, then tapping the regeneration power of an ample body of therapeutic stem cells.
http://www.gamida-cell.com/  May 15, 2008 9:52AM EST

4. Bioprocess Engineering - Biotechnology is defined by the tools used to practice it. By programming DNA and directing cellular machinery, we can obtain products that were unimaginable even 10 years ago. With biotechnology, we can direct the nanoscale machinery of living cells to produce self-contained factories that perform on a characteristic scale of one micron. To be useful to people, however, bioproducts and bioenergy must be produced in immense quantities. Genetic engineering, for example, is carried out at a molecular scale but is amplified through bioprocess engineering to transfer the technology from the test tube to the bottle through a sequence of integrated steps that generate, recover, purify and package the product (NRC, 1992). The challenge facing bioengineers is to redirect genetic and cellular machinery to make economically important molecules when the cells are placed in controlled environments. Engineers must design, build, and operate hardware and integrated systems that can multiply a cell’s output by a factor of one trillion, as well as recover and purify the products in a cost-effective manner. Bioprocess engineering is the next frontier.

Ladisch, Michael. “The Role of Bioprocess Engineering in Biotechnology.” The Bridge – National Academy of Engineering Publication. Volume 34, Number 3 - Fall 2004
http://www.nae.edu/NAE/bridgecom.nsf/...  March 11, 2008 11:07AM EST

5. Bioreactor – n. (1974) a devise or apparatus in which living organisms and esp. bacteria synthesize useful substances (as interferon) or break down harmful ones (as in sewage).
Merriam Webster’s Collegiate Dictionary Eleventh Edition. Massachusetts: Merriam-Webster Inc., 2005: 124.

6. Perfuse – v. 1. To pour or diffuse a liquid over or through something. 2. To force blood or other fluid to flow from the artery through the vascular bed of a tissue or to flow through the lumen of a hollow structure.
The American Heritage STEDMAN’S Medical Dictionary. Boston, New York: Houghton Mifflin Company, 2004: 613.

7. Hydroxyapatite – n. The principal bone salt that provides the compressional strength of vertebrate bone.
The American Heritage STEDMAN’S Medical Dictionary. Boston, New York: Houghton Mifflin Company, 2004: 380.

 

Bio

Professor Dame Julia M Polak FMedSciProfessor Dame Julia M. Polak, FMedSci, DBE was educated at the University of Buenos Aires, before moving to London. She is married to Professor Daniel Catovsky, and has three children. Prof. Polak is one of the longest surviving recipients of a heart and lung transplant in the United Kingdom. It was her transplant in 1995 which caused her to change her career direction from Pathology towards the newly developing field of Tissue Engineering. She is currently head of the Centre for Tissue Engineering and Regenerative Medicine at Imperial College London, a centre for medical research she set up with Professor Larry Hench, also from Imperial College, to develop cells and tissues for transplantation into humans.

 

 

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