TY - JOUR
T1 - A Melt-electrowritten Filter for Capture and Culture of Circulating Colon Cancer Cells
AU - Jørgensen, Mathias Lindh
AU - Müller, Christoph Alexander
AU - Nøddesbo, Mille Sikkersoq Kimer
AU - Nadzieja, Marcin
AU - Zhang, Zhongyang
AU - Su, Yingchun
AU - Just, Jesper
AU - Spindler, Karen-Lise Garm
AU - Chen, Menglin
N1 - © 2020 The Author(s).
PY - 2020/3
Y1 - 2020/3
N2 - Metastasis is the major cause of death in cancer patients accounting for about 90% of the mortality. The detection and analysis of the hallmark of metastasis, circulating tumor cells (CTCs), have significant impact in cancer biology and clinical practice. However, the scarcity of CTCs in blood, particularly in that of colorectal cancer patients, is a serious bottleneck in the development of CTC-based precision medicine. Herein, the melt electrowriting (MEW) technology was used for reproductive fabrication of a biocompatible antibody-presenting polycaprolactone filter with tailored porous structure. It is demonstrated, for the first time, that such filter can be used not only to catch cancer cells spiked in whole blood but also to culture the cancer cells directly on site. Specifically, HT29 colon cancer cells can be captured with an efficiency of 85%, and when spiked into 4 mL of whole blood, 47% were captured on one Ø12mm filter. Furthermore, repeated capture and culture experiments have shown that as few as 20 HT29 colon cancer cells spiked into 4 mL of whole blood can be captured on the filter and within 2 weeks be expanded on site to become tumor bodies that are visible to the untrained eye. This filter allows for downstream analysis, such as flow cytometry, immunocytochemistry, Western blotting, and rt-qPCR. This technology represents a simple and cost-effective platform that potentially enables fast and efficient culture of rare CTCs from patients’ blood. This provides non-invasive alternatives for solid biopsy tumor materials for treatment screening, with great potential to realize precision medicine for cancer treatment.
AB - Metastasis is the major cause of death in cancer patients accounting for about 90% of the mortality. The detection and analysis of the hallmark of metastasis, circulating tumor cells (CTCs), have significant impact in cancer biology and clinical practice. However, the scarcity of CTCs in blood, particularly in that of colorectal cancer patients, is a serious bottleneck in the development of CTC-based precision medicine. Herein, the melt electrowriting (MEW) technology was used for reproductive fabrication of a biocompatible antibody-presenting polycaprolactone filter with tailored porous structure. It is demonstrated, for the first time, that such filter can be used not only to catch cancer cells spiked in whole blood but also to culture the cancer cells directly on site. Specifically, HT29 colon cancer cells can be captured with an efficiency of 85%, and when spiked into 4 mL of whole blood, 47% were captured on one Ø12mm filter. Furthermore, repeated capture and culture experiments have shown that as few as 20 HT29 colon cancer cells spiked into 4 mL of whole blood can be captured on the filter and within 2 weeks be expanded on site to become tumor bodies that are visible to the untrained eye. This filter allows for downstream analysis, such as flow cytometry, immunocytochemistry, Western blotting, and rt-qPCR. This technology represents a simple and cost-effective platform that potentially enables fast and efficient culture of rare CTCs from patients’ blood. This provides non-invasive alternatives for solid biopsy tumor materials for treatment screening, with great potential to realize precision medicine for cancer treatment.
KW - Bioconjugation
KW - Circulating tumor cells
KW - Colorectal cancer
KW - Melt electrospinning writing
KW - On-site culture
KW - Polycaprolactone
KW - EX-VIVO CULTURE
KW - COLORECTAL-CANCER
KW - EXPANSION
KW - TUMOR-CELLS
KW - FIBROCYTES
KW - CTCS
U2 - 10.1016/j.mtbio.2020.100052
DO - 10.1016/j.mtbio.2020.100052
M3 - Journal article
C2 - 32490373
SN - 2590-0064
VL - 6
JO - Materials Today Bio
JF - Materials Today Bio
M1 - 100052
ER -