Mesenchymal stem/stromal cells from human pluripotent stem cell-derived brain organoid enhance the ex vivo expansion and maintenance of hematopoietic stem/progenitor cells

• Brain organoid-derived MSCs (pMSCs) exhibit neural crest origin and support robust ex vivo expansion of UCB-CD34+ HSPCs, outperforming umbilical cord MSCs. • pMSCs maintain HSPC transplantability in long-term culture, as evidenced by in vivo engraftment in immunodeficient mice. • pMSCs provide an improved hematopoietic microenvironment via high expression of Wnt inhibitors SFRP1 and SFRP2, which modulate cell cycle to promote HSPC maintenance. • This study offers a scalable, homogeneous source of MSCs from hPSCs for potential therapeutic applications in HSPC expansion and transplantation.