TY - JOUR
T1 - Modeling Human Gonad Development in Organoids
AU - Pryzhkova, Marina V.
AU - Boers, Romina
AU - Jordan, Philip W.
N1 - Funding Information:
We are grateful to Dr. A. Leung and Dr. V. Busa, as well as Dr. J. Wang and Dr. Honghe Liu for help with qPCR equipment setup and data collection. We would like to thank Dr. B. Zirkin and Dr. J.-Y. Chung for help with ELISA equipment setup and data collection. We thank Dr. I. Rasool from WRTC and Dr. Hooper from JHU Legacy Gift Rapid Autopsy program for coordinating the acquisition of deidentified human testis samples used for this study. Additionally, we would like to acknowledge Dr. M. Matunis for critical discussion of project design. This work was funded by the American Society for Reproductive Medicine to MVP (KY Cha Award in Stem Cell Technology) and National Institute of General Medical Sciences grant to PWJ (R01GM11755).
Funding Information:
We are grateful to Dr. A. Leung and Dr. V. Busa, as well as Dr. J. Wang and Dr. Honghe Liu for help with qPCR equipment setup and data collection. We would like to thank Dr. B. Zirkin and Dr. J.-Y. Chung for help with ELISA equipment setup and data collection. We thank Dr. I. Rasool from WRTC and Dr. Hooper from JHU Legacy Gift Rapid Autopsy program for coordinating the acquisition of deidentified human testis samples used for this study. Additionally, we would like to acknowledge Dr. M. Matunis for critical discussion of project design. This work was funded by the American Society for Reproductive Medicine to MVP (KY Cha Award in Stem Cell Technology) and National Institute of General Medical Sciences grant to PWJ (R01GM11755).
Publisher Copyright:
© 2022, Korean Tissue Engineering and Regenerative Medicine Society.
PY - 2022/12
Y1 - 2022/12
N2 - BACKGROUND:: Our learning about human reproductive development is greatly hampered due to the absence of an adequate model. Animal studies cannot truthfully recapitulate human developmental processes, and studies of human fetal tissues are limited by their availability and ethical restrictions. Innovative three-dimensional (3D) organoid technology utilizing human pluripotent stem cells (hPSCs) offered a new approach to study tissue and organ development in vitro. However, a system for modeling human gonad development has not been established, thus, limiting our ability to study causes of infertility. METHODS:: In our study we utilized the 3D hPSC organoid culture in mini-spin bioreactors. Relying on intrinsic self-organizing and differentiation capabilities of stem cells, we explored whether organoids could mimic the development of human embryonic and fetal gonad. RESULTS:: We have developed a simple, bioreactor-based organoid system for modeling early human gonad development. Male hPSC-derived organoids follow the embryonic gonad developmental trajectory and differentiate into multipotent progenitors, which further specialize into testicular supporting and interstitial cells. We demonstrated functional activity of the generated cell types by analyzing the expression of cell type-specific markers. Furthermore, the specification of gonadal progenitors in organoid culture was accompanied by the characteristic architectural tissue organization. CONCLUSION:: This organoid system opens the opportunity for detailed studies of human gonad and germ cell development that can advance our understanding of sex development disorders. Implementation of human gonad organoid technology could be extended to modeling causes of infertility and regenerative medicine applications.
AB - BACKGROUND:: Our learning about human reproductive development is greatly hampered due to the absence of an adequate model. Animal studies cannot truthfully recapitulate human developmental processes, and studies of human fetal tissues are limited by their availability and ethical restrictions. Innovative three-dimensional (3D) organoid technology utilizing human pluripotent stem cells (hPSCs) offered a new approach to study tissue and organ development in vitro. However, a system for modeling human gonad development has not been established, thus, limiting our ability to study causes of infertility. METHODS:: In our study we utilized the 3D hPSC organoid culture in mini-spin bioreactors. Relying on intrinsic self-organizing and differentiation capabilities of stem cells, we explored whether organoids could mimic the development of human embryonic and fetal gonad. RESULTS:: We have developed a simple, bioreactor-based organoid system for modeling early human gonad development. Male hPSC-derived organoids follow the embryonic gonad developmental trajectory and differentiate into multipotent progenitors, which further specialize into testicular supporting and interstitial cells. We demonstrated functional activity of the generated cell types by analyzing the expression of cell type-specific markers. Furthermore, the specification of gonadal progenitors in organoid culture was accompanied by the characteristic architectural tissue organization. CONCLUSION:: This organoid system opens the opportunity for detailed studies of human gonad and germ cell development that can advance our understanding of sex development disorders. Implementation of human gonad organoid technology could be extended to modeling causes of infertility and regenerative medicine applications.
KW - Gonad development
KW - Human pluripotent stem cells
KW - Mesonephros
KW - Mini-spin bioreactor
KW - Testis organoid model
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UR - http://www.scopus.com/inward/citedby.url?scp=85141596505&partnerID=8YFLogxK
U2 - 10.1007/s13770-022-00492-y
DO - 10.1007/s13770-022-00492-y
M3 - Article
C2 - 36350469
AN - SCOPUS:85141596505
SN - 1738-2696
VL - 19
SP - 1185
EP - 1206
JO - Tissue Engineering and Regenerative Medicine
JF - Tissue Engineering and Regenerative Medicine
IS - 6
ER -