While kidney transplantation is currently the most effective therapy for end-stage renal disease, WFIRM scientists are looking for better options due to the shortage of donor organs and the side effects of anti-rejection drugs. The kidney is a good example of how our scientists are pursuing multiple strategies to bring treatment to patients.

“Recycling” Discarded Organs
One strategy is to use discarded organs from humans as a platform for organ engineering. The process starts by removing all cells from the organ, leaving the “shell” of the organ to create a scaffold. Crucial microvessels, vital to filtering contaminants, were left intact after the scrubbing process, while growth factors, needed to maintain function,were also retained. The patient’s own cells can then be expanded and used to repopulate the scaffolds.

3D Bioprinting Replacement Kidneys
Another strategy is to print replacement organs using a 3D bioprinter. Our scientists have successfully bioprinted muscle, bone and cartilage that, when implanted in animals, developed a system of nerves and blood vessels. They are currently working on more complex structures, like kidneys.

Partial Augmentation Strategy
In a proof-of-concept study, WFIRM researchers showed the feasibility of bioengineering vascularized functional renal tissues for kidney regeneration, developing a partial augmentation strategy that may be a more feasible and practical approach than creating whole organs.

The scientists created a novel collagen-based vascular scaffold – a mold – that is structurally identical to native kidney that was able to develop vascularized tissue. They showed that the vascular scaffolds integrated with the host vessels and supported renal cell viability. The results are promising and support continued exploration of this method to further evaluate the improvement of renal function.

Cell and Molecular Therapy
WFIRM scientists were the first in the world to identify, characterize and harness the unique properties of stem cells derived from amniotic fluid and the placenta and have developed techniques for isolation and expansion of the cells. Amnion-derived stem cells can be used as a universal cell source because they have the ability to become different cell types as well as the ability to be anti-inflammatory, making them a potential source for regeneration.

Scientists also developed a system to isolate normal cells from end-stage failure kidneys. The cells can be expanded, grown outside the body, and then delivered in a gel solution into the same patient. They demonstrated in a pre-clinical model that cell therapy treatment had positive effects on functional improvement and structural recovery of the kidney. This therapy is currently in human clinical trials in order to prevent patients with diagnosed kidney failure from progressing to dialysis and transplantation.

WFIRM has a long history of collaboration and a leadership role with the Department of Defense and the Armed Forces. It leads the Armed Forces Institute of Regenerative Medicine (AFIRM), a consortium of more than 30 academic institutions and industry partners to deliver regenerative-based technologies leading to functional and aesthetic recovery from injuries incurred in military service.

Two phases of AFIRM research programs led to 25 clinical trials and hundreds of patients who received treatment with AFIRM-funded technologies. AFIRM focuses on developing clinical therapies in the following areas: Reconstruction for facial and skull injuries through tissue regeneration; Regeneration of skin for burn injuries; New treatments to prevent rejection of “composite” transplants such as face and hands; Restoration of function to severely traumatized limbs; and Reconstruction of the genital and urinary organs and lower abdomen.

The U.S. Department of Health and Human Services (HHS) is funding research for WFIRM’s lung-on-a-chip technology as a model to develop chemical injury treatments. The multi-year program from the Biomedical Advanced Research and Development Authority (BARDA), part of the HHS Office of the Assistant Secretary for Preparedness and Response, validates how the lung-on-a-chip technology works in modeling the effects of chlorine gas to develop treatments. This model can be engineered to reflect both normal and diseased tissue and includes innate immune system responsiveness, and accurate and reproducible response to drugs and toxins.

An award from the Defense Threat Reduction Agency (DTRA), a part of the Department of Defense, supports WFIRM’s research and development program to study the ways in which a virus invades and infects humans. The Pathogenesis and Toxicity Forecasting Using Multi-Organoid Systems (PATMOS) program uses WFIRM’s body-on-a-chip platform to investigate the biochemical changes that take place in viral infections.

The PATMOS program will infect the 3D organs, or organoids, with different viruses and analyze what happens throughout the course of an infection. Biochemical changes taking place at the molecular and cellular level will be tracked and the data fed into Artificial Intelligence modeling which will begin to learn the complicated interplay of these subtle changes. The research program will provide a valuable tool for maintaining the health and safety of US service members and could offer new strategies for combating future viral pandemics.