August 24, 2014

expert reaction to thymus grown in mice from lab-created cells

A study in Nature Cell Biology reported the reprogramming and transplant of cells to grow a thymus in mice.

Prof Robin Lovell-Badge, Head of Developmental Genetics at the MRC National Institute for Medical Research (NIMR), said:

“This appears to be an excellent study, combining several approaches, each of which has been known to work in other systems, but with the result that they have produced functional thymus-like organs in mice with a major component (the thymic epithelial cells) originating from reprogrammed embryonic fibroblasts.

“This is an important achievement both for demonstrating how to make an organ, albeit a relatively simple one, and because of the critical role of the thymus in developing a proper functioning immune system.  However, especially because it was necessary to combine the reprogrammed thymic epithelial cells with other cell types, notably fetal derived cells (corresponding to thymic mesenchyme) in order to have development of a thymus-like organ after transplantation, the methods are unlikely to be easy to translate to human patients. They may also need to begin with a source of fibroblasts to reprogram that is patient-specific, although perhaps immune rejection will not be a problem as the thymus is involved in generating tolerance. Nevertheless, this is a very promising start.”

Dr Paolo de Coppi, Consultant Paediatric Surgeon at Great Ormond Street Hospital, and Head of Stem Cells and Regenerative Medicine at the Institute of Child Health, said:

“Research such as this demonstrates that organ engineering could, in the future, be a substitute for transplantation, overcoming problems such as organ donor shortages and bypassing the need for immunosuppressive therapy.

“The direct reprogramming technique shown in this paper is attractive because the possibility of generating specialised cells from stem cells opens the door to wider application of organ engineering even when matched tissue-specific cells are not available.

“Engineering of relatively simple organs has already been adopted for a small number of patients and it is possible that within the next five years more complex organs will be engineered for patients using specialised cells derived from stem cells in a similar way as outlined in this paper.

“It remains to be seen whether, in the long term, cells generated using direct reprogramming will be able to maintain their specialised form and avoid problems such as tumour formation.”

Prof Chris Mason, Professor of Regenerative Medicine at University College London, said:

“Stem cell scientists are finally overcoming the complexity of the immune system to potentially produce therapies that will dramatically transform patients’ lives. Using living cells as therapies has the big advantage in that the functionality of cells is many orders of magnitude greater than that of conventional drugs. Nowhere is this level of functionality more needed than in curing disorders of the immune system.

“For the last couple of years, clinical trials of T cell therapies for end-stage leukaemia have demonstrated the power of cell therapy to eradicate widespread disease. The Bredenkamp paper further pushes out the cell therapy boundaries by producing in the lab, cells capable of growing into a new thymus once implanted into a mouse. Should this work in patients, the potential to boost a weak immune system would have a major impact on a number of difficult to treat conditions including inherited thymus disorders in children and in immuno-compromised cancer patients. The major advantage would be a once-only, off-the-shelf, cell transplant compared to the current practice of tracking down potential donors who may then prove unsuitable or may not be found in time.

“The time and resources required to turn this mouse proof of concept study into a safe and effective routine therapy for patients will be very significant – ten years and tens of millions of pounds at a bare minimum. Even the starting point, the underpinning science, is far from complete: for example, not all the cells that are required can yet be made in the lab.  However, the Bredenkamp data strongly supports the urgent need for more scientists, together with engineers and clinicians, to now get involved in order to evaluate and develop this new technology, and if appropriate, accelerate its journey into the clinic for the benefit of tens of thousands of patients worldwide.”

‘An organized and functional thymus generated from FOXN1-reprogrammed fibroblasts’ by Nicholas Bredenkamp et al. published in Nature Cell Biology on Sunday 24 August 2014.

Declared interests

None declared