Page 18 - X. Stem cell biology

[X. Stem cell biology-11]

Stem cell spheroids loaded with quercetin microparticles

exert potent protective effects against murine colitis model

and induce the generation of wound-healing epithelial cells

in intestinal organoid

Ji-Su Ahn¹˙#, Yoojin Seo²˙#, Su-jeong Oh¹, Ye Young Shin¹, Ji Won Yang¹, Jee-Heon Jeong³˙*, Hyung-Sik Kim¹˙²˙*

¹Department of Life Science in Dentistry, Pusan National University, Yangsan 50612, Republic of Korea, ²Dental and

Life Science Institute, Pusan National University, Yangsan 50612, Republic of Korea, ³College of Pharmacy,
Yeungnam University, Gyeongsan 38541, Republic of Korea

Tissue repairing capacity and immunomodulatory effects of mesenchymal stem cells (MSCs) have been exploited

for the treatment of various inflammatory disorders; however, inconsistent therapeutic outcomes due to low
engraftment rate often restrain their clinical potential. To overcome these limitations, 3D spheroid culture was

applied to augment longevity of MSCs. Then we designed a novel strategy to create heterospheroids (HS) that
consists of MSCs and microspheres containing quercetin (QUR), a potent anti-oxidative agent. Notably, HS showed

enhanced cell viability with reduced senescence-associated phenotype and oxidative stress-induced apoptosis.
Interestingly, MSCHS provided better therapeutic outcomes compared to MSC3D, partially due to their enhanced

survival capacity. Moreover, MSC3D and MSCHS stimulated the epithelial regeneration process by inducing
specialized tissue-repairing cells so-called wound-associated epithelial cells (WAE) through the robust production

of PGE2 in an ex vivo intestinal organoid system. Taken together, we suggest a convergent strategy of MSCHS
formation with ROS scavenger QUR, which can maximize the inflammation-attenuating and regeneration-

accelerating abilities of MSCs, as well as their engraftment after transplantation.