한빛사논문
- 조회513
Jin Won Kim, Sun Ah Nam, Jawoon Yi, Jae Yun Kim, Jong Young Lee, Seo-Yeon Park, Tugce Sen, Yoo-mi Choi, Jae Yeon Lee, Hong Lim Kim, Hyung Wook Kim, Jiwhan Park,* Dong-Woo Cho,* and Yong Kyun Kim*
J. W. Kim, S. A. Nam, J. Y. Lee, S.-Y. Park, Y. K. Kim
Cell Death Disease Research Center College of Medicine The Catholic University of Korea Seoul 06591, Korea
J. Yi, J. Park
School of Life Sciences Gwangju Institute of Science and Technology Gwangju 61005, Korea
J. Y. Kim, D.-W. Cho
School of Interdisciplinary Bioscience and Bioengineering Pohang University of Science and Technology Pohang 790-784, Korea
T. Sen, D.-W. Cho
Department of Mechanical Engineering Pohang University of Science and Technology (POSTECH) Pohang, Kyungbuk 790-784, Korea
Y.-mi Choi
Department of Convergence IT Engineering Pohang University of Science and Technology Pohang 790-784, Korea
J. Y. Lee
Department of Companion Animal Health Daegu Haany University Gyeongsan 790-784, Republic of Korea
H. L. Kim
Integrative Research Support Center College of Medicine The Catholic University of Korea Seoul 06591, Korea
H. W. Kim, Y. K. Kim
Department of Internal Medicine The Catholic University of Korea St. Vincent’s Hospital, Suwon 16247, Korea
J.W.K., S.A.N., J.Y., and J.Y.K. contributed equally to this work.
*Corresponding author.
Abstract
Kidney organoids derived from human pluripotent stem cells (hPSCs) have extensive potential for disease modelling and regenerative medicine. However, the limited vascularization and immaturity of kidney organoids have been still remained to overcome. Extracellular matrix (ECM) can provide mechanical support and a biochemical microenvironment for cell growth and differentiation. Here in vitro methods using a kidney decellularized extracellular matrix (dECM) hydrogel to culture hPSC-derived kidney organoids, which have extensive vascular network and their own endothelial cells, are reported. Single-cell transcriptomics reveal that the vascularized kidney organoids cultured using the kidney dECM have more mature patterns of glomerular development and higher similarity to human kidney than those cultured without the kidney dECM. Differentiation of α-galactosidase A (GLA)-knock-out hPSCs generated using CRISPR/Cas9 into kidney organoids by the culture method using kidney dECM efficiently recapitulate Fabry nephropathy with vasculopathy. Transplantation of kidney organoids with kidney dECM into kidney of mouse accelerates the recruitment of endothelial cells from the host mouse kidney and maintains vascular integrity with the more organized slit diaphragm-like structures than those without kidney dECM. The kidney dECM methodology for inducing extensive vascularization and maturation of kidney organoids can be applied to studies for kidney development, disease modeling, and regenerative medicine.
논문정보
- Research article
- 2022년 03월 (BRIC 등록일 2022-03-30)
- 국내 연구진
- 의약학 > 재생의학
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