한빛사논문
- 조회375
영남대학교
Duc-Vinh Pham 1,7,8, Prakash Shrestha 2,8, Thi-Kem Nguyen 1, Junhyeung Park 2, Mahesh Pandit 1, Jae-Hoon Chang 1, Soo Young Kim 1, Dong-Young Choi 1, Sung Soo Han 3,4, Inho Choi 3,5, Gyu Hwan Park 6, Jee-Heon Jeong 2, Pil-Hoon Park 1,3
1College of Pharmacy, Yeungnam University, Gyeongsan 38541, Republic of Korea
2Department of Precision Medicine, School of Medicine, Sungkyunkwan University, Suwon 16419, Republic of Korea
3Research Institute of Cell Culture, Yeungnam University, Gyeongsan 38541, Republic of Korea
4School of Chemical Engineering, Yeungnam University, Gyeongsan 38541, Republic of Korea
5Department of Medical Biotechnology, Yeungnam University, Gyeongsan 38541, Republic of Korea
6College of Pharmacy, Research Institute of Pharmaceutical Sciences, Kyungpook National University, Daegu 41566, Republic of Korea
7Department of Pharmacology, Hanoi University of Pharmacy, Hanoi, Viet Nam
8These authors contributed equally
Corresponding author Pil-Hoon Park, PhD, Jee-Heon Jeong
Abstract
Mesenchymal stem cells (MSCs) are ubiquitous multipotent cells that exhibit significant therapeutic potentials in a variety of disorders. Nevertheless, their clinical efficacy is limited owing to poor survival, low rate of engraftment, and impaired potency upon transplantation. Spheroidal three-dimensional (3D) culture of MSCs (MSC3D) has been proven to better preserve their in vivo functional properties. However, the molecular mechanisms underlying the improvement in MSC function by spheroid formation are not clearly understood. NLRP3 inflammasomes, a key component of the innate immune system, have recently been shown to play a role in cell fate decision of MSCs. The present study examined the role of NLRP3 inflammasomes in the survival and potency of MSC spheroids. We found that MSC3D led to decreased activation of NLRP3 inflammasomes through alleviation of ER stress in an autophagy-dependent manner. Importantly, downregulation of NLRP3 inflammasomes signaling critically contributes to the enhanced survival rate in MSC3D through modulation of pyroptosis and apoptosis. The critical role of NLRP3 inflammasome suppression in the enhanced therapeutic efficacy of MSC spheroids was further confirmed in an in vivo mouse model of DSS-induced colitis. These findings suggest that 3D culture confers survival and functional advantages to MSCs by suppressing NLRP3 inflammasome activation.
논문정보
- Research article
- 2022년 12월 (BRIC 등록일 2023-02-15)
- 국내(교신)+국외 연구진
- 의약학 > 약학
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