A pilot study of 3D tissue-engineered bone marrow culture as a tool to predict patient response to therapy in multiple myeloma

Abstract Cancer patients undergo detrimental toxicities and ineffective treatments especially in the relapsed setting, due to failed treatment attempts. The development of a tool that predicts the clinical response of individual patients to therapy is greatly desired. We have developed a novel patie...

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Autores principales: Kinan Alhallak, Amanda Jeske, Pilar de la Puente, Jennifer Sun, Mark Fiala, Feda Azab, Barbara Muz, Ilyas Sahin, Ravi Vij, John F. DiPersio, Abdel Kareem Azab
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Publicado: Nature Portfolio 2021
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spelling oai:doaj.org-article:d949d57f50c147fba308ccbe7e50a8772021-12-02T17:17:38ZA pilot study of 3D tissue-engineered bone marrow culture as a tool to predict patient response to therapy in multiple myeloma10.1038/s41598-021-98760-92045-2322https://doaj.org/article/d949d57f50c147fba308ccbe7e50a8772021-09-01T00:00:00Zhttps://doi.org/10.1038/s41598-021-98760-9https://doaj.org/toc/2045-2322Abstract Cancer patients undergo detrimental toxicities and ineffective treatments especially in the relapsed setting, due to failed treatment attempts. The development of a tool that predicts the clinical response of individual patients to therapy is greatly desired. We have developed a novel patient-derived 3D tissue engineered bone marrow (3DTEBM) technology that closely recapitulate the pathophysiological conditions in the bone marrow and allows ex vivo proliferation of tumor cells of hematologic malignancies. In this study, we used the 3DTEBM to predict the clinical response of individual multiple myeloma (MM) patients to different therapeutic regimens. We found that while no correlation was observed between in vitro efficacy in classic 2D culture systems of drugs used for MM with their clinical efficacious concentration, the efficacious concentration in the 3DTEBM were directly correlated. Furthermore, the 3DTEBM model retrospectively predicted the clinical response to different treatment regimens in 89% of the MM patient cohort. These results demonstrated that the 3DTEBM is a feasible platform which can predict MM clinical responses with high accuracy and within a clinically actionable time frame. Utilization of this technology to predict drug efficacy and the likelihood of treatment failure could significantly improve patient care and treatment in many ways, particularly in the relapsed and refractory setting. Future studies are needed to validate the 3DTEBM model as a tool for predicting clinical efficacy.Kinan AlhallakAmanda JeskePilar de la PuenteJennifer SunMark FialaFeda AzabBarbara MuzIlyas SahinRavi VijJohn F. DiPersioAbdel Kareem AzabNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 11, Iss 1, Pp 1-10 (2021)
institution DOAJ
collection DOAJ
language EN
topic Medicine
R
Science
Q
spellingShingle Medicine
R
Science
Q
Kinan Alhallak
Amanda Jeske
Pilar de la Puente
Jennifer Sun
Mark Fiala
Feda Azab
Barbara Muz
Ilyas Sahin
Ravi Vij
John F. DiPersio
Abdel Kareem Azab
A pilot study of 3D tissue-engineered bone marrow culture as a tool to predict patient response to therapy in multiple myeloma
description Abstract Cancer patients undergo detrimental toxicities and ineffective treatments especially in the relapsed setting, due to failed treatment attempts. The development of a tool that predicts the clinical response of individual patients to therapy is greatly desired. We have developed a novel patient-derived 3D tissue engineered bone marrow (3DTEBM) technology that closely recapitulate the pathophysiological conditions in the bone marrow and allows ex vivo proliferation of tumor cells of hematologic malignancies. In this study, we used the 3DTEBM to predict the clinical response of individual multiple myeloma (MM) patients to different therapeutic regimens. We found that while no correlation was observed between in vitro efficacy in classic 2D culture systems of drugs used for MM with their clinical efficacious concentration, the efficacious concentration in the 3DTEBM were directly correlated. Furthermore, the 3DTEBM model retrospectively predicted the clinical response to different treatment regimens in 89% of the MM patient cohort. These results demonstrated that the 3DTEBM is a feasible platform which can predict MM clinical responses with high accuracy and within a clinically actionable time frame. Utilization of this technology to predict drug efficacy and the likelihood of treatment failure could significantly improve patient care and treatment in many ways, particularly in the relapsed and refractory setting. Future studies are needed to validate the 3DTEBM model as a tool for predicting clinical efficacy.
format article
author Kinan Alhallak
Amanda Jeske
Pilar de la Puente
Jennifer Sun
Mark Fiala
Feda Azab
Barbara Muz
Ilyas Sahin
Ravi Vij
John F. DiPersio
Abdel Kareem Azab
author_facet Kinan Alhallak
Amanda Jeske
Pilar de la Puente
Jennifer Sun
Mark Fiala
Feda Azab
Barbara Muz
Ilyas Sahin
Ravi Vij
John F. DiPersio
Abdel Kareem Azab
author_sort Kinan Alhallak
title A pilot study of 3D tissue-engineered bone marrow culture as a tool to predict patient response to therapy in multiple myeloma
title_short A pilot study of 3D tissue-engineered bone marrow culture as a tool to predict patient response to therapy in multiple myeloma
title_full A pilot study of 3D tissue-engineered bone marrow culture as a tool to predict patient response to therapy in multiple myeloma
title_fullStr A pilot study of 3D tissue-engineered bone marrow culture as a tool to predict patient response to therapy in multiple myeloma
title_full_unstemmed A pilot study of 3D tissue-engineered bone marrow culture as a tool to predict patient response to therapy in multiple myeloma
title_sort pilot study of 3d tissue-engineered bone marrow culture as a tool to predict patient response to therapy in multiple myeloma
publisher Nature Portfolio
publishDate 2021
url https://doaj.org/article/d949d57f50c147fba308ccbe7e50a877
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