SOME LIMITATIONS:

-All experiments done with a single source of hPSCs - limits generalizability
-NOD-SCID mice have multiple immune deficits, would NPCs behave similarly in "regular" mice (or humans)?👥
-Less than 15% of cells in the transplant were NPC-derived kidney cells. What were the rest?🤔

PART 4: MECHANISM OF BENEFIT

Surprisingly, the NPCs did not integrate with the host kidney. Instead, they were found to produces VEGF-A after transplantation. VEGF-A hydrogels without NPCs could protect from AKI, and genetic inactivation of VEGF-A in NPCs greatly reduced their benefits.

PART 3: TREATING KIDNEY DISEASE

Using a mouse🐁 model of AKI (cisplatin), they made the surprising finding that histologic tubular damage and serum creatinine can be improved by NPC injection and NOT terminal organoids. Similarly, NPCs could improve fibrosis in a model of CKD (aristocholic acid)

Part 2: PURIFYING NPCs USING c-MET

One problem with hPSC technology is that cells don't always behave consistently. Planning for cases where cells don't differentiate to NPCs well, they found a protein specific to NPCs, "c-MET", that could be use to purify them using a technology called FACS.

PART 1: MAKING BETTER NPCs

Aiming to treat humans with kidney disease, they realized they would need to make tons of NPCs. So they first improved the method of growing these OSR1+SIX2+ NPCs in large numbers, using "CFY" media💧 containing:
C: Canonical Wnt agonist
F: FGF9
Y: ROCK1/2 inhibitor

BACKGROUND:

Human pluripotent stem cells (hPSCs) can generate any tissue - including the kidney🫘. To do this, they must first specialize into nephron progenitors (NPCs), which are kidney-specific stem cells (can't make other organs).

The authors published on this before
e.g. tinyurl.com/4ufzv9pf

HIGHLIGHTS:

• A new culture medium (food for cells) helps nephron progenitors (NPCs) to grow in vitro
• An new protein ("c-MET") can be used to purify NPCs
• Transplanting NPCs attenuates acute (AKI) and chronic (CKD) kidney disease in mice
• VEGF-A mediates this

More details below ⬇️

🙌 Thanks for following this kidney-organoid deep-dive!
What grabbed you most, and which papers or topics should Pluripotency unpack next?
Drop ideas below or DM anytime.
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FINAL THOUGHTS:

- Important advances on methods to generate NPCs
- Could this become a new cell therapy in kidney disease?💉
- If VEGF-A is the key, do we really need kidney organoids, or can find another way to give it?
- More work needed to make functional, integrating kidney tissue from hPSCs! 👩‍🔬

📣 NEW PAPER ALERT! 🧵
I love kidney organoids - tiny nephron clusters grown in the lab from pluripotent stem cells. But can they treat kidney disease? New data suggests they can (in mice)!
Let's dive in ⬇️
tinyurl.com/mr3sd6vu
#KidneyOrganoids #CellTherapy #ChronicKidneyDisease #AcuteKidneyInjury