Rion found that culturing stem cells in a lab to force division leads to rapid DNA damage, as cells are not designed for this artificial environment. This damage created inconsistent exosome products, making large-scale, uniform manufacturing from stem cells unfeasible and prompting a search for a more stable source.

Unlike external machines, implanting parts internally triggers the body's powerful defenses. The immune system attacks foreign objects, and blood forms clots around non-native surfaces. These two biological responses are the biggest design hurdles for internal replacement parts, problems that external devices like dialysis machines don't face.

Launching an autologous cell therapy is complex, involving a nephrologist, a biopsy doctor, and an interventional radiologist. ProKidney's CEO notes success requires standardizing this process to ensure a seamless, best-in-class experience for both the patient and all involved providers, which may mean a slower, more deliberate initial rollout.

CZI's New York Biohub is treating the immune system as a programmable platform. They are engineering cells to navigate the body, detect disease markers like heart plaques, record this information in their DNA, and then be read externally, creating a living diagnostic tool.

Despite exciting early efficacy data for in vivo CAR-T therapies, the modality's future hinges on the critical unanswered question of durability. How long the therapeutic effects last, for which there is little data, will ultimately determine its clinical viability and applications in cancer versus autoimmune diseases.

Rion strategically chose diabetic foot ulcers as its lead indication to de-risk its new therapeutic class. This "outside-in" approach allows the company to build a substantial safety record and gain regulatory and clinical acceptance with a topical product before advancing to more complex systemic applications.

Rion avoids disrupting the medical platelet supply by sourcing near-expiration units from blood banks. This provides an abundant, low-cost raw material. In return, blood banks gain a revenue stream for products that would be discarded, encouraging them to maintain larger inventories for transfusions, creating a win-win.

To combat immunosuppressive "cold" tumors, new trispecific antibodies are emerging. Unlike standard T-cell engagers that only provide the primary CD3 activation signal, these drugs also deliver the crucial co-stimulatory signal (e.g., via CD28), ensuring full T-cell activation in microenvironments where this second signal is naturally absent.

Rion's research, initially focused on stem cells, revealed their regenerative properties were not intrinsic. Instead, the cells were recycling platelet content from their culture medium, and these recycled components were the true source of the therapeutic effect. This finding prompted a strategic pivot away from stem cells.