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Organotypic and Microphysiological Human Tissue Models for Drug Discovery and Development—Current State-of-the-Art and Future Perspectives
Sonia Youhanna, Aurino M. Kemas, Lena Preiss, Yitian Zhou, Joanne X. Shen, Selgin D. Cakal, Francesco S. Paqualini, Sravan K. Goparaju, Reza Zandi Shafagh, Johan Ulrik Lind, Carl M. Sellgren and Volker M. Lauschke
Gunnar Schulte, ASSOCIATE EDITOR
Pharmacological Reviews January 2022, 74 (1) 141-206; DOI: https://doi.org/10.1124/pharmrev.120.000238
Sonia Youhanna
Department of Physiology and Pharmacology, Karolinska Institutet, Stockholm, Sweden (S.Y., A.M.K., L.P., Y.Z., J.X.S., S.K.G., R.Z.S., C.M.S., V.M.L.); Department of Drug Metabolism and Pharmacokinetics (DMPK), Merck KGaA, Darmstadt, Germany (L.P.); Department of Health Technology, Technical University of Denmark, Lyngby, Denmark (S.D.C., J.U.L.); Synthetic Physiology Laboratory, Department of Civil Engineering and Architecture, University of Pavia, Pavia, Italy (F.S.P.); Division of Micro- and Nanosystems, KTH Royal Institute of Technology, Stockholm, Sweden (Z.S.); and Dr Margarete Fischer-Bosch Institute of Clinical Pharmacology, Stuttgart, Germany (V.M.L.)
Aurino M. Kemas
Department of Physiology and Pharmacology, Karolinska Institutet, Stockholm, Sweden (S.Y., A.M.K., L.P., Y.Z., J.X.S., S.K.G., R.Z.S., C.M.S., V.M.L.); Department of Drug Metabolism and Pharmacokinetics (DMPK), Merck KGaA, Darmstadt, Germany (L.P.); Department of Health Technology, Technical University of Denmark, Lyngby, Denmark (S.D.C., J.U.L.); Synthetic Physiology Laboratory, Department of Civil Engineering and Architecture, University of Pavia, Pavia, Italy (F.S.P.); Division of Micro- and Nanosystems, KTH Royal Institute of Technology, Stockholm, Sweden (Z.S.); and Dr Margarete Fischer-Bosch Institute of Clinical Pharmacology, Stuttgart, Germany (V.M.L.)
Lena Preiss
Department of Physiology and Pharmacology, Karolinska Institutet, Stockholm, Sweden (S.Y., A.M.K., L.P., Y.Z., J.X.S., S.K.G., R.Z.S., C.M.S., V.M.L.); Department of Drug Metabolism and Pharmacokinetics (DMPK), Merck KGaA, Darmstadt, Germany (L.P.); Department of Health Technology, Technical University of Denmark, Lyngby, Denmark (S.D.C., J.U.L.); Synthetic Physiology Laboratory, Department of Civil Engineering and Architecture, University of Pavia, Pavia, Italy (F.S.P.); Division of Micro- and Nanosystems, KTH Royal Institute of Technology, Stockholm, Sweden (Z.S.); and Dr Margarete Fischer-Bosch Institute of Clinical Pharmacology, Stuttgart, Germany (V.M.L.)
Yitian Zhou
Department of Physiology and Pharmacology, Karolinska Institutet, Stockholm, Sweden (S.Y., A.M.K., L.P., Y.Z., J.X.S., S.K.G., R.Z.S., C.M.S., V.M.L.); Department of Drug Metabolism and Pharmacokinetics (DMPK), Merck KGaA, Darmstadt, Germany (L.P.); Department of Health Technology, Technical University of Denmark, Lyngby, Denmark (S.D.C., J.U.L.); Synthetic Physiology Laboratory, Department of Civil Engineering and Architecture, University of Pavia, Pavia, Italy (F.S.P.); Division of Micro- and Nanosystems, KTH Royal Institute of Technology, Stockholm, Sweden (Z.S.); and Dr Margarete Fischer-Bosch Institute of Clinical Pharmacology, Stuttgart, Germany (V.M.L.)
Joanne X. Shen
Department of Physiology and Pharmacology, Karolinska Institutet, Stockholm, Sweden (S.Y., A.M.K., L.P., Y.Z., J.X.S., S.K.G., R.Z.S., C.M.S., V.M.L.); Department of Drug Metabolism and Pharmacokinetics (DMPK), Merck KGaA, Darmstadt, Germany (L.P.); Department of Health Technology, Technical University of Denmark, Lyngby, Denmark (S.D.C., J.U.L.); Synthetic Physiology Laboratory, Department of Civil Engineering and Architecture, University of Pavia, Pavia, Italy (F.S.P.); Division of Micro- and Nanosystems, KTH Royal Institute of Technology, Stockholm, Sweden (Z.S.); and Dr Margarete Fischer-Bosch Institute of Clinical Pharmacology, Stuttgart, Germany (V.M.L.)
Selgin D. Cakal
Department of Physiology and Pharmacology, Karolinska Institutet, Stockholm, Sweden (S.Y., A.M.K., L.P., Y.Z., J.X.S., S.K.G., R.Z.S., C.M.S., V.M.L.); Department of Drug Metabolism and Pharmacokinetics (DMPK), Merck KGaA, Darmstadt, Germany (L.P.); Department of Health Technology, Technical University of Denmark, Lyngby, Denmark (S.D.C., J.U.L.); Synthetic Physiology Laboratory, Department of Civil Engineering and Architecture, University of Pavia, Pavia, Italy (F.S.P.); Division of Micro- and Nanosystems, KTH Royal Institute of Technology, Stockholm, Sweden (Z.S.); and Dr Margarete Fischer-Bosch Institute of Clinical Pharmacology, Stuttgart, Germany (V.M.L.)
Francesco S. Paqualini
Department of Physiology and Pharmacology, Karolinska Institutet, Stockholm, Sweden (S.Y., A.M.K., L.P., Y.Z., J.X.S., S.K.G., R.Z.S., C.M.S., V.M.L.); Department of Drug Metabolism and Pharmacokinetics (DMPK), Merck KGaA, Darmstadt, Germany (L.P.); Department of Health Technology, Technical University of Denmark, Lyngby, Denmark (S.D.C., J.U.L.); Synthetic Physiology Laboratory, Department of Civil Engineering and Architecture, University of Pavia, Pavia, Italy (F.S.P.); Division of Micro- and Nanosystems, KTH Royal Institute of Technology, Stockholm, Sweden (Z.S.); and Dr Margarete Fischer-Bosch Institute of Clinical Pharmacology, Stuttgart, Germany (V.M.L.)
Sravan K. Goparaju
Department of Physiology and Pharmacology, Karolinska Institutet, Stockholm, Sweden (S.Y., A.M.K., L.P., Y.Z., J.X.S., S.K.G., R.Z.S., C.M.S., V.M.L.); Department of Drug Metabolism and Pharmacokinetics (DMPK), Merck KGaA, Darmstadt, Germany (L.P.); Department of Health Technology, Technical University of Denmark, Lyngby, Denmark (S.D.C., J.U.L.); Synthetic Physiology Laboratory, Department of Civil Engineering and Architecture, University of Pavia, Pavia, Italy (F.S.P.); Division of Micro- and Nanosystems, KTH Royal Institute of Technology, Stockholm, Sweden (Z.S.); and Dr Margarete Fischer-Bosch Institute of Clinical Pharmacology, Stuttgart, Germany (V.M.L.)
Reza Zandi Shafagh
Department of Physiology and Pharmacology, Karolinska Institutet, Stockholm, Sweden (S.Y., A.M.K., L.P., Y.Z., J.X.S., S.K.G., R.Z.S., C.M.S., V.M.L.); Department of Drug Metabolism and Pharmacokinetics (DMPK), Merck KGaA, Darmstadt, Germany (L.P.); Department of Health Technology, Technical University of Denmark, Lyngby, Denmark (S.D.C., J.U.L.); Synthetic Physiology Laboratory, Department of Civil Engineering and Architecture, University of Pavia, Pavia, Italy (F.S.P.); Division of Micro- and Nanosystems, KTH Royal Institute of Technology, Stockholm, Sweden (Z.S.); and Dr Margarete Fischer-Bosch Institute of Clinical Pharmacology, Stuttgart, Germany (V.M.L.)
Johan Ulrik Lind
Department of Physiology and Pharmacology, Karolinska Institutet, Stockholm, Sweden (S.Y., A.M.K., L.P., Y.Z., J.X.S., S.K.G., R.Z.S., C.M.S., V.M.L.); Department of Drug Metabolism and Pharmacokinetics (DMPK), Merck KGaA, Darmstadt, Germany (L.P.); Department of Health Technology, Technical University of Denmark, Lyngby, Denmark (S.D.C., J.U.L.); Synthetic Physiology Laboratory, Department of Civil Engineering and Architecture, University of Pavia, Pavia, Italy (F.S.P.); Division of Micro- and Nanosystems, KTH Royal Institute of Technology, Stockholm, Sweden (Z.S.); and Dr Margarete Fischer-Bosch Institute of Clinical Pharmacology, Stuttgart, Germany (V.M.L.)
Carl M. Sellgren
Department of Physiology and Pharmacology, Karolinska Institutet, Stockholm, Sweden (S.Y., A.M.K., L.P., Y.Z., J.X.S., S.K.G., R.Z.S., C.M.S., V.M.L.); Department of Drug Metabolism and Pharmacokinetics (DMPK), Merck KGaA, Darmstadt, Germany (L.P.); Department of Health Technology, Technical University of Denmark, Lyngby, Denmark (S.D.C., J.U.L.); Synthetic Physiology Laboratory, Department of Civil Engineering and Architecture, University of Pavia, Pavia, Italy (F.S.P.); Division of Micro- and Nanosystems, KTH Royal Institute of Technology, Stockholm, Sweden (Z.S.); and Dr Margarete Fischer-Bosch Institute of Clinical Pharmacology, Stuttgart, Germany (V.M.L.)
Volker M. Lauschke
Department of Physiology and Pharmacology, Karolinska Institutet, Stockholm, Sweden (S.Y., A.M.K., L.P., Y.Z., J.X.S., S.K.G., R.Z.S., C.M.S., V.M.L.); Department of Drug Metabolism and Pharmacokinetics (DMPK), Merck KGaA, Darmstadt, Germany (L.P.); Department of Health Technology, Technical University of Denmark, Lyngby, Denmark (S.D.C., J.U.L.); Synthetic Physiology Laboratory, Department of Civil Engineering and Architecture, University of Pavia, Pavia, Italy (F.S.P.); Division of Micro- and Nanosystems, KTH Royal Institute of Technology, Stockholm, Sweden (Z.S.); and Dr Margarete Fischer-Bosch Institute of Clinical Pharmacology, Stuttgart, Germany (V.M.L.)
Gunnar Schulte
Roles: ASSOCIATE EDITOR

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In this issue
Review ArticleReview Article
3D Human Tissue Models
Sonia Youhanna, Aurino M. Kemas, Lena Preiss, Yitian Zhou, Joanne X. Shen, Selgin D. Cakal, Francesco S. Paqualini, Sravan K. Goparaju, Reza Zandi Shafagh, Johan Ulrik Lind, Carl M. Sellgren and Volker M. Lauschke
Pharmacological Reviews January 1, 2022, 74 (1) 141-206; DOI: https://doi.org/10.1124/pharmrev.120.000238
Review ArticleReview Article
3D Human Tissue Models
Sonia Youhanna, Aurino M. Kemas, Lena Preiss, Yitian Zhou, Joanne X. Shen, Selgin D. Cakal, Francesco S. Paqualini, Sravan K. Goparaju, Reza Zandi Shafagh, Johan Ulrik Lind, Carl M. Sellgren and Volker M. Lauschke
Pharmacological Reviews January 1, 2022, 74 (1) 141-206; DOI: https://doi.org/10.1124/pharmrev.120.000238
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- Article
- Abstract
- I. Introduction
- II. Liver
- III. Kidney
- IV. Intestine
- V. Brain
- VI. Heart
- VII. Skeletal Muscle
- VIII. Fluidic Integration of Organotypic Tissue Models
- IX. Bioprinting as a Novel Modality for the Generation of Organotypic Cultures
- X. Technical Considerations for Culture Devices
- XI. Conclusions and Perspectives
- Authorship Contributions
- Footnotes
- Abbreviations
- References
- Figures & Data
- Info & Metrics
- eLetters
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