Organoids as a new model for improving regenerative medicine and cancer personalized therapy in renal diseases

Ludovica Grassi, Romina Alfonsi, Federica Francescangeli, Michele Signore, Maria Laura De Angelis, Antonio Addario, Manuela Costantini, Elisabetta Flex, Andrea Ciolfi, Simone Pizzi, Alessandro Bruselles, Matteo Pallocca, Giuseppe Simone, Mustapha Haoui, Mario Falchi, Michele Milella, Steno Sentinelli, Paola Di Matteo, Emilia Stellacci, Michele Gallucci & 4 others Giovanni Muto, Marco Tartaglia, Ruggero De Maria, Désirée Bonci

Research output: Contribution to journalArticle

Abstract

The pressure towards innovation and creation of new model systems in regenerative medicine and cancer research has fostered the development of novel potential therapeutic applications. Kidney injuries provoke a high request of organ transplants making it the most demanding system in the field of regenerative medicine. Furthermore, renal cancer frequently threaten patients' life and aggressive forms still remain difficult to treat. Ethical issues related to the use of embryonic stem cells, has fueled research on adult, patient-specific pluripotent stem cells as a model for discovery and therapeutic development, but to date, normal and cancerous renal experimental models are lacking. Several research groups are focusing on the development of organoid cultures. Since organoids mimic the original tissue architecture in vitro, they represent an excellent model for tissue engineering studies and cancer therapy testing. We established normal and tumor renal cell carcinoma organoids previously maintained in a heterogeneous multi-clone stem cell-like enriching medium. Starting from adult normal kidney specimens, we were able to isolate and propagate organoid 3D-structures composed of both differentiated and undifferentiated cells while expressing nephron specific markers. Furthermore, we were capable to establish organoids derived from cancer tissues although with a success rate inferior to that of their normal counterpart. Cancer cultures displayed epithelial and mesenchymal phenotype while retaining tumor specific markers. Of note, tumor organoids recapitulated neoplastic masses when orthotopically injected into immunocompromised mice. Our data suggest an innovative approach of long-term establishment of normal- and cancer-derived renal organoids obtained from cultures of fleshly dissociated adult tissues. Our results pave the way to organ replacement pioneering strategies as well as to new models for studying drug-induced nephrotoxicity and renal diseases. Along similar lines, deriving organoids from renal cancer patients opens unprecedented opportunities for generation of preclinical models aimed at improving therapeutic treatments.

Original languageEnglish
Pages (from-to)201
JournalCell death & disease
Volume10
Issue number3
DOIs
Publication statusPublished - Feb 27 2019

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Organoids
Regenerative Medicine
Kidney
Kidney Neoplasms
Neoplasms
Therapeutics
Research
Pluripotent Stem Cells
Nephrons
Tissue Engineering
Embryonic Stem Cells
Tumor Biomarkers
Renal Cell Carcinoma
Ethics
Theoretical Models
Stem Cells
Clone Cells
Transplants
Phenotype
Pressure

Cite this

@article{44e55e89e11d437ba1bcce69336b2cbe,
title = "Organoids as a new model for improving regenerative medicine and cancer personalized therapy in renal diseases",
abstract = "The pressure towards innovation and creation of new model systems in regenerative medicine and cancer research has fostered the development of novel potential therapeutic applications. Kidney injuries provoke a high request of organ transplants making it the most demanding system in the field of regenerative medicine. Furthermore, renal cancer frequently threaten patients' life and aggressive forms still remain difficult to treat. Ethical issues related to the use of embryonic stem cells, has fueled research on adult, patient-specific pluripotent stem cells as a model for discovery and therapeutic development, but to date, normal and cancerous renal experimental models are lacking. Several research groups are focusing on the development of organoid cultures. Since organoids mimic the original tissue architecture in vitro, they represent an excellent model for tissue engineering studies and cancer therapy testing. We established normal and tumor renal cell carcinoma organoids previously maintained in a heterogeneous multi-clone stem cell-like enriching medium. Starting from adult normal kidney specimens, we were able to isolate and propagate organoid 3D-structures composed of both differentiated and undifferentiated cells while expressing nephron specific markers. Furthermore, we were capable to establish organoids derived from cancer tissues although with a success rate inferior to that of their normal counterpart. Cancer cultures displayed epithelial and mesenchymal phenotype while retaining tumor specific markers. Of note, tumor organoids recapitulated neoplastic masses when orthotopically injected into immunocompromised mice. Our data suggest an innovative approach of long-term establishment of normal- and cancer-derived renal organoids obtained from cultures of fleshly dissociated adult tissues. Our results pave the way to organ replacement pioneering strategies as well as to new models for studying drug-induced nephrotoxicity and renal diseases. Along similar lines, deriving organoids from renal cancer patients opens unprecedented opportunities for generation of preclinical models aimed at improving therapeutic treatments.",
author = "Ludovica Grassi and Romina Alfonsi and Federica Francescangeli and Michele Signore and {De Angelis}, {Maria Laura} and Antonio Addario and Manuela Costantini and Elisabetta Flex and Andrea Ciolfi and Simone Pizzi and Alessandro Bruselles and Matteo Pallocca and Giuseppe Simone and Mustapha Haoui and Mario Falchi and Michele Milella and Steno Sentinelli and {Di Matteo}, Paola and Emilia Stellacci and Michele Gallucci and Giovanni Muto and Marco Tartaglia and {De Maria}, Ruggero and D{\'e}sir{\'e}e Bonci",
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day = "27",
doi = "10.1038/s41419-019-1453-0",
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T1 - Organoids as a new model for improving regenerative medicine and cancer personalized therapy in renal diseases

AU - Grassi, Ludovica

AU - Alfonsi, Romina

AU - Francescangeli, Federica

AU - Signore, Michele

AU - De Angelis, Maria Laura

AU - Addario, Antonio

AU - Costantini, Manuela

AU - Flex, Elisabetta

AU - Ciolfi, Andrea

AU - Pizzi, Simone

AU - Bruselles, Alessandro

AU - Pallocca, Matteo

AU - Simone, Giuseppe

AU - Haoui, Mustapha

AU - Falchi, Mario

AU - Milella, Michele

AU - Sentinelli, Steno

AU - Di Matteo, Paola

AU - Stellacci, Emilia

AU - Gallucci, Michele

AU - Muto, Giovanni

AU - Tartaglia, Marco

AU - De Maria, Ruggero

AU - Bonci, Désirée

PY - 2019/2/27

Y1 - 2019/2/27

N2 - The pressure towards innovation and creation of new model systems in regenerative medicine and cancer research has fostered the development of novel potential therapeutic applications. Kidney injuries provoke a high request of organ transplants making it the most demanding system in the field of regenerative medicine. Furthermore, renal cancer frequently threaten patients' life and aggressive forms still remain difficult to treat. Ethical issues related to the use of embryonic stem cells, has fueled research on adult, patient-specific pluripotent stem cells as a model for discovery and therapeutic development, but to date, normal and cancerous renal experimental models are lacking. Several research groups are focusing on the development of organoid cultures. Since organoids mimic the original tissue architecture in vitro, they represent an excellent model for tissue engineering studies and cancer therapy testing. We established normal and tumor renal cell carcinoma organoids previously maintained in a heterogeneous multi-clone stem cell-like enriching medium. Starting from adult normal kidney specimens, we were able to isolate and propagate organoid 3D-structures composed of both differentiated and undifferentiated cells while expressing nephron specific markers. Furthermore, we were capable to establish organoids derived from cancer tissues although with a success rate inferior to that of their normal counterpart. Cancer cultures displayed epithelial and mesenchymal phenotype while retaining tumor specific markers. Of note, tumor organoids recapitulated neoplastic masses when orthotopically injected into immunocompromised mice. Our data suggest an innovative approach of long-term establishment of normal- and cancer-derived renal organoids obtained from cultures of fleshly dissociated adult tissues. Our results pave the way to organ replacement pioneering strategies as well as to new models for studying drug-induced nephrotoxicity and renal diseases. Along similar lines, deriving organoids from renal cancer patients opens unprecedented opportunities for generation of preclinical models aimed at improving therapeutic treatments.

AB - The pressure towards innovation and creation of new model systems in regenerative medicine and cancer research has fostered the development of novel potential therapeutic applications. Kidney injuries provoke a high request of organ transplants making it the most demanding system in the field of regenerative medicine. Furthermore, renal cancer frequently threaten patients' life and aggressive forms still remain difficult to treat. Ethical issues related to the use of embryonic stem cells, has fueled research on adult, patient-specific pluripotent stem cells as a model for discovery and therapeutic development, but to date, normal and cancerous renal experimental models are lacking. Several research groups are focusing on the development of organoid cultures. Since organoids mimic the original tissue architecture in vitro, they represent an excellent model for tissue engineering studies and cancer therapy testing. We established normal and tumor renal cell carcinoma organoids previously maintained in a heterogeneous multi-clone stem cell-like enriching medium. Starting from adult normal kidney specimens, we were able to isolate and propagate organoid 3D-structures composed of both differentiated and undifferentiated cells while expressing nephron specific markers. Furthermore, we were capable to establish organoids derived from cancer tissues although with a success rate inferior to that of their normal counterpart. Cancer cultures displayed epithelial and mesenchymal phenotype while retaining tumor specific markers. Of note, tumor organoids recapitulated neoplastic masses when orthotopically injected into immunocompromised mice. Our data suggest an innovative approach of long-term establishment of normal- and cancer-derived renal organoids obtained from cultures of fleshly dissociated adult tissues. Our results pave the way to organ replacement pioneering strategies as well as to new models for studying drug-induced nephrotoxicity and renal diseases. Along similar lines, deriving organoids from renal cancer patients opens unprecedented opportunities for generation of preclinical models aimed at improving therapeutic treatments.

U2 - 10.1038/s41419-019-1453-0

DO - 10.1038/s41419-019-1453-0

M3 - Article

VL - 10

SP - 201

JO - Cell Death and Disease

JF - Cell Death and Disease

SN - 2041-4889

IS - 3

ER -