874,000 people die each year from heart disease
2,600 patients wait for approximately 2,300 hearts each year
159,000 people die each year from lung cancer
3,100 patients wait for approximately 1,400 lungs each year
28,000 people die each year from chronic liver disease
17,000 patients wait for approximately 6,500 livers each year
44,000 people die each year from kidney disease
7,000 patients wait for approximately 17,000 kidneys each year
The breadth and depth of the applications for the Miromatrix technology is staggering. It will enable the replacement of entire organs (e.g. heart; liver; kidney; pancreas) with non-transplantable organs harvested from either animals or donors, stripped of their cells and recellularized with either cells from the recipient or compatible donor cells. The potential market for the Miromatrix organ replacement technology is enormous and, due to the lack of an efficacious alternative, largely untapped.
Two and one-half years ago, an article was published in Nature Medicine that described the research done in a laboratory at the University of Minnesota. The article stunned both the scientific community and the lay press, both of which were effusive with their praise and made the authors of the article overnight celebrities. Harald Ott and Doris Taylor had removed the heart from a recently euthanized animal, decellularized it, and then injected it with a mixture of heart cells from a donor rat. After only eight days in a bioreactor, the heart began to beat again.
The novel and proprietary technology that made it possible to create a new heart is known as perfusion decellularization. This method of decellularizing any vascularized tissue, up to and including whole organs, is protected by a series of patent applications prepared by Fish & Richardson in all major markets, and has been licensed to a Minnesota based company, Miromatrix Medical, on a worldwide, exclusive basis.
In summary, perfusion decellularization involves passing a mild detergent through an organs native vascular system to remove all cellular components. The process leaves behind a scaffold of extracellular matrix that retains the original architecture, mechanical properties and vascular network of the organ, which is critical for the recellularization and growth of a new functional organ.
Miromatrix’ breakthrough technology is in contrast to the previous method used for decellularization known as “immersion decellularization.” For many years researchers have attempted to use nature’s scaffold as the ultimate building block for tissue engineering and regenerative medicine because artificial matrices for cells have not been successful due primarily to their inability to reproduce the complex structure of a biological organ. These efforts, however, have achieved only limited success with small sections of tissues and never a whole organ. The problem is not in the theory, but in the condition of the scaffold following decellularization. During immersion decellularization an organ is immersed in a vat of harsh detergent solution where the process of decellularization is diffusion-limited as the detergent slowly migrates from the outer surface inward and then back out once the cellular material is dissolved. In addition to the removal of the organ capsule through mechanical or enzymatic methods, the cells within the organ begin to break down before being exposed to the detergent, releasing various proteases that also degrade the surrounding scaffold. The end result is a partially degraded scaffold with a compromised vascular network and outer organ capsule that will not maintain physiological pressures when tested. In addition, cells no longer recognize this degraded scaffold as the appropriate environment to become functional.
Miromatrix’ perfusion decellularization technology overcomes these hurdles by facilitating rapid access to the whole organ through the native vasculature by cannulating the artery and running a mild detergent solution through the blood vessels as opposed to immersing the organ. Because most cells are located within 100 μm of a capillary, the result is an exponential increase in the effective surface area of the detergent and a decreased resident time as the dissolved cellular material is expelled through the venous system (as opposed to through the organ capsule). This results in the rapid decellularization of an organ from the inside-out. The end result is a completely preserved native scaffold containing the appropriate microenvironment required for the introduction of organ specific cells, along with an intact vascular network and outer capsule capable of maintaining physiological pressures. These components are critical for the later use of Miromatrix’ recellularization technology where vascular and organ specific regenerative cells are repopulated onto the organ scaffold, homing to the appropriate microenvironment (since the “signals” that inform a cell what to do remain), as the organs are grown and matured in bioreactors under normal physiological conditions.