Promises of Ex Vivo Organ Generation

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Regenerative medicine and bioengineering offer a chance to redefine the human lifespan.
Posted On: December 20, 2016
By Michael Chang, ORT Science Writer and UHN Trainee
 
Medical and public health advances through the 20th century have helped extend life expectancy to the point where the limits of the human lifespan may have been realized1. A major limiting factor to continued health and longevity is organ failure2. Doctors cannot yet repair damaged organs, but can fortunately completely replace one with a donor organ and provide patients with an improved quality of life and significant life extension3. Sadly, the number of available donor organs is insufficient to meet the overwhelming demand for replacement organs. According to the Canadian Institute for Health Information, only one-third of Canadians requiring an organ transplant receive it.

To address the rising need for organs, scientists offer the promise of growing personalized replacement organs in sophisticated bioreactors designed to mimic the environment inside a body. The current method is based on the recellularization of a structural framework (scaffold) with stem cells4. The scaffold is typically acquired by stripping a donor organ of its original cells with a detergent to isolate the extracellular matrix (ECM) with bound biomolecules5. In theory, the biologically relevant factors on the scaffold’s natural ECM can be used to direct the development of cells into a functional organ, while it is housed in a bioreactor. The organ, made from stems cells of a patient, can then be subsequently transplanted back into the patient without any risk of rejection. These personalized organs would ensure a perfect match every time and completely eliminate the life-long need for immunosuppressive drugs.
 
In practice, however, successful recellularization of scaffolds into functional complex organs (e.g. heart, liver, kidney, and lung) have not yet been established. Future studies implanting organs grown outside of the body (ex vivo) will be needed to demonstrate proof of concept. Additionally, a major caveat of this technology is that organ donors are still required; with the existing shortage of organ donors, the number of available organs is limited. Animal organs have been considered, but humans cells may not be able to fully develop on xenogeneic scaffolds6. Furthermore, if xenogeneic scaffolds from more closely related species could successfully facilitate the growth of human cells into functional organs, serious ethical, social, and political issues would need to be considered7, 8. Notwithstanding these difficulties, the recellularization of a scaffold into a functional complex organ still proves incredibly promising given that the urinary bladder9 and other complex tissues10 have been grown ex vivo and implanted into individuals with clinical success. The ability to grow organs ex vivo has the potential to be one of the greatest medical achievements of our century.

Even if the ultimate goal of recellularizing a scaffold back into a functional complex organ is not realized, the endeavour itself will contribute greatly towards the advancement of regenerative medicine. Researchers can use future discoveries to develop in-body tissue repair on the natural scaffold of organs, or to grow the ECM and cells concurrently into functional organs, and maybe even redefine the physical limits of the human lifespan in the process.