5-Aminolevulinic acid tumor paint and photodynamic therapy for myxofibrosarcoma: an in vitro study
Abstract Background 5-Aminolevulinic acid (5-ALA), a fluorescent contrast agent, has been used for tumor paint and photodynamic therapy (PDT) for various tumors, but its use with soft tissue sarcomas is not well documented. Myxofibrosarcoma, a subtype of soft tissue sarcoma with a high local recurre...
| Main Authors: | , , , , , , |
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| Format: | Article |
| Language: | English |
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BMC
2020-03-01
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| Series: | Journal of Orthopaedic Surgery and Research |
| Subjects: | |
| Online Access: | http://link.springer.com/article/10.1186/s13018-020-01606-9 |
| _version_ | 1798038517552513024 |
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| author | Shachar Kenan Haixiang Liang Howard J. Goodman Andrew J. Jacobs Amanda Chan Daniel A. Grande Adam S. Levin |
| author_facet | Shachar Kenan Haixiang Liang Howard J. Goodman Andrew J. Jacobs Amanda Chan Daniel A. Grande Adam S. Levin |
| author_sort | Shachar Kenan |
| collection | DOAJ |
| description | Abstract Background 5-Aminolevulinic acid (5-ALA), a fluorescent contrast agent, has been used for tumor paint and photodynamic therapy (PDT) for various tumors, but its use with soft tissue sarcomas is not well documented. Myxofibrosarcoma, a subtype of soft tissue sarcoma with a high local recurrence rate, may benefit from similar types of treatment. The purpose of this study was to analyze the effects of 5-ALA tumor paint and PDT on a myxofibrosarcoma cell line. Methods Tumor paint was assessed by exposing micromass pellets of human adipose-derived stromal (ADS) cells or myxofibrosarcoma (MUG-Myx1) cells to 5-ALA. Cell pellets were then visualized using a microscope at established excitation and emission wavelengths. Corrected total cell fluorescence was calculated per accepted protocols. Photodynamic therapy was similarly assessed by exposing ADS and MUG-Myx1 cells to 5-ALA, with subsequent analysis via flow cytometry and real-time confocal microscopy. Results The use of 5-ALA tumor paint led to a selective fluorescence in MUG-Myx1 cells. Findings were confirmed by flow cytometry. Interestingly, flow cytometry results showed progressive selective cell death with increasing 5-ALA exposure as a result of the PDT effect. PDT was further confirmed using confocal microscopy, which revealed progressive cellular bubble formation consistent with advancing stages of cell death—a finding that was not seen in control ADS cells. Conclusions 5-ALA tumor paint and PDT were successfully used on a human myxofibrosarcoma cell line (MUG-Myx1). Results from this study showed both selective fluorescent tagging and selective cytotoxicity of 5-ALA toward malignant myxofibrosarcoma cells, while sparing benign adipose control cells. This finding was further confirmed in a dramatic time-lapse video, visually confirming active, targeted cell death. 5-ALA’s two-pronged application of selective tumor identification and cytotoxicity may transform surgical and medical approaches for treating soft tissue sarcomas. |
| first_indexed | 2024-04-11T21:41:17Z |
| format | Article |
| id | doaj.art-a39aed4702b4465795dae8be523eb7bc |
| institution | Directory Open Access Journal |
| issn | 1749-799X |
| language | English |
| last_indexed | 2024-04-11T21:41:17Z |
| publishDate | 2020-03-01 |
| publisher | BMC |
| record_format | Article |
| series | Journal of Orthopaedic Surgery and Research |
| spelling | doaj.art-a39aed4702b4465795dae8be523eb7bc2022-12-22T04:01:35ZengBMCJournal of Orthopaedic Surgery and Research1749-799X2020-03-011511810.1186/s13018-020-01606-95-Aminolevulinic acid tumor paint and photodynamic therapy for myxofibrosarcoma: an in vitro studyShachar Kenan0Haixiang Liang1Howard J. Goodman2Andrew J. Jacobs3Amanda Chan4Daniel A. Grande5Adam S. Levin6Department of Orthopaedic Surgery, North Shore-Long Island Jewish Hospital, Northwell Health SystemOrthopaedic Research Laboratory, The Feinstein Institute for Medical ResearchDepartment of Orthopaedic Surgery, North Shore-Long Island Jewish Hospital, Northwell Health SystemHofstra Northwell School of Medicine, 500 Hofstra UniversityMicroscopy Facility, The Feinstein Institute for Medical ResearchOrthopaedic Research Laboratory, The Feinstein Institute for Medical ResearchDepartment of Orthopaedic Surgery and Oncology, The Johns Hopkins University School of MedicineAbstract Background 5-Aminolevulinic acid (5-ALA), a fluorescent contrast agent, has been used for tumor paint and photodynamic therapy (PDT) for various tumors, but its use with soft tissue sarcomas is not well documented. Myxofibrosarcoma, a subtype of soft tissue sarcoma with a high local recurrence rate, may benefit from similar types of treatment. The purpose of this study was to analyze the effects of 5-ALA tumor paint and PDT on a myxofibrosarcoma cell line. Methods Tumor paint was assessed by exposing micromass pellets of human adipose-derived stromal (ADS) cells or myxofibrosarcoma (MUG-Myx1) cells to 5-ALA. Cell pellets were then visualized using a microscope at established excitation and emission wavelengths. Corrected total cell fluorescence was calculated per accepted protocols. Photodynamic therapy was similarly assessed by exposing ADS and MUG-Myx1 cells to 5-ALA, with subsequent analysis via flow cytometry and real-time confocal microscopy. Results The use of 5-ALA tumor paint led to a selective fluorescence in MUG-Myx1 cells. Findings were confirmed by flow cytometry. Interestingly, flow cytometry results showed progressive selective cell death with increasing 5-ALA exposure as a result of the PDT effect. PDT was further confirmed using confocal microscopy, which revealed progressive cellular bubble formation consistent with advancing stages of cell death—a finding that was not seen in control ADS cells. Conclusions 5-ALA tumor paint and PDT were successfully used on a human myxofibrosarcoma cell line (MUG-Myx1). Results from this study showed both selective fluorescent tagging and selective cytotoxicity of 5-ALA toward malignant myxofibrosarcoma cells, while sparing benign adipose control cells. This finding was further confirmed in a dramatic time-lapse video, visually confirming active, targeted cell death. 5-ALA’s two-pronged application of selective tumor identification and cytotoxicity may transform surgical and medical approaches for treating soft tissue sarcomas.http://link.springer.com/article/10.1186/s13018-020-01606-95-Aminolevulinic acidMyxofibrosarcomaNeoadjuvant therapyPhotodynamic therapySarcomaTumor paint |
| spellingShingle | Shachar Kenan Haixiang Liang Howard J. Goodman Andrew J. Jacobs Amanda Chan Daniel A. Grande Adam S. Levin 5-Aminolevulinic acid tumor paint and photodynamic therapy for myxofibrosarcoma: an in vitro study Journal of Orthopaedic Surgery and Research 5-Aminolevulinic acid Myxofibrosarcoma Neoadjuvant therapy Photodynamic therapy Sarcoma Tumor paint |
| title | 5-Aminolevulinic acid tumor paint and photodynamic therapy for myxofibrosarcoma: an in vitro study |
| title_full | 5-Aminolevulinic acid tumor paint and photodynamic therapy for myxofibrosarcoma: an in vitro study |
| title_fullStr | 5-Aminolevulinic acid tumor paint and photodynamic therapy for myxofibrosarcoma: an in vitro study |
| title_full_unstemmed | 5-Aminolevulinic acid tumor paint and photodynamic therapy for myxofibrosarcoma: an in vitro study |
| title_short | 5-Aminolevulinic acid tumor paint and photodynamic therapy for myxofibrosarcoma: an in vitro study |
| title_sort | 5 aminolevulinic acid tumor paint and photodynamic therapy for myxofibrosarcoma an in vitro study |
| topic | 5-Aminolevulinic acid Myxofibrosarcoma Neoadjuvant therapy Photodynamic therapy Sarcoma Tumor paint |
| url | http://link.springer.com/article/10.1186/s13018-020-01606-9 |
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