Colorectal Cancer Bioengineered Microtissues as a Model to Replicate Tumor-ECM Crosstalk and Assess Drug Delivery Systems In Vitro
Current 3D cancer models (in vitro) fail to reproduce complex cancer cell extracellular matrices (ECMs) and the interrelationships occurring (in vivo) in the tumor microenvironment (TME). Herein, we propose 3D in vitro colorectal cancer microtissues (3D CRC μTs), which reproduce the TME more faithfu...
| Main Authors: | , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
MDPI AG
2023-03-01
|
| Series: | International Journal of Molecular Sciences |
| Subjects: | |
| Online Access: | https://www.mdpi.com/1422-0067/24/6/5678 |
| _version_ | 1797611278842200064 |
|---|---|
| author | Alessia La Rocca Vincenza De Gregorio Elena Lagreca Raffaele Vecchione Paolo Antonio Netti Giorgia Imparato |
| author_facet | Alessia La Rocca Vincenza De Gregorio Elena Lagreca Raffaele Vecchione Paolo Antonio Netti Giorgia Imparato |
| author_sort | Alessia La Rocca |
| collection | DOAJ |
| description | Current 3D cancer models (in vitro) fail to reproduce complex cancer cell extracellular matrices (ECMs) and the interrelationships occurring (in vivo) in the tumor microenvironment (TME). Herein, we propose 3D in vitro colorectal cancer microtissues (3D CRC μTs), which reproduce the TME more faithfully in vitro. Normal human fibroblasts were seeded onto porous biodegradable gelatin microbeads (GPMs) and were continuously induced to synthesize and assemble their own ECMs (3D Stroma μTs) in a spinner flask bioreactor. Then, human colon cancer cells were dynamically seeded onto the 3D Stroma μTs to achieve the 3D CRC μTs. Morphological characterization of the 3D CRC μTs was performed to assess the presence of different complex macromolecular components that feature in vivo in the ECM. The results showed the 3D CRC μTs recapitulated the TME in terms of ECM remodeling, cell growth, and the activation of normal fibroblasts toward an activated phenotype. Then, the microtissues were assessed as a drug screening platform by evaluating the effect of 5-Fluorouracil (5-FU), curcumin-loaded nanoemulsions (CT-NE-Curc), and the combination of the two. When taken together, the results showed that our microtissues are promising in that they can help clarify complex cancer–ECM interactions and evaluate the efficacy of therapies. Moreover, they may be combined with tissue-on-chip technologies aimed at addressing further studies in cancer progression and drug discovery. |
| first_indexed | 2024-03-11T06:25:39Z |
| format | Article |
| id | doaj.art-f6887f3e028542ddab8e1c048fe4aa5d |
| institution | Directory Open Access Journal |
| issn | 1661-6596 1422-0067 |
| language | English |
| last_indexed | 2024-03-11T06:25:39Z |
| publishDate | 2023-03-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | International Journal of Molecular Sciences |
| spelling | doaj.art-f6887f3e028542ddab8e1c048fe4aa5d2023-11-17T11:37:28ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672023-03-01246567810.3390/ijms24065678Colorectal Cancer Bioengineered Microtissues as a Model to Replicate Tumor-ECM Crosstalk and Assess Drug Delivery Systems In VitroAlessia La Rocca0Vincenza De Gregorio1Elena Lagreca2Raffaele Vecchione3Paolo Antonio Netti4Giorgia Imparato5Center for Advanced Biomaterials for Health Care (CABHC), Istituto Italiano di Tecnologia, 80125 Napoli, ItalyInterdisciplinary Research Centre on Biomaterials (CRIB), University of Naples Federico II, 80125 Naples, ItalyCenter for Advanced Biomaterials for Health Care (CABHC), Istituto Italiano di Tecnologia, 80125 Napoli, ItalyCenter for Advanced Biomaterials for Health Care (CABHC), Istituto Italiano di Tecnologia, 80125 Napoli, ItalyCenter for Advanced Biomaterials for Health Care (CABHC), Istituto Italiano di Tecnologia, 80125 Napoli, ItalyCenter for Advanced Biomaterials for Health Care (CABHC), Istituto Italiano di Tecnologia, 80125 Napoli, ItalyCurrent 3D cancer models (in vitro) fail to reproduce complex cancer cell extracellular matrices (ECMs) and the interrelationships occurring (in vivo) in the tumor microenvironment (TME). Herein, we propose 3D in vitro colorectal cancer microtissues (3D CRC μTs), which reproduce the TME more faithfully in vitro. Normal human fibroblasts were seeded onto porous biodegradable gelatin microbeads (GPMs) and were continuously induced to synthesize and assemble their own ECMs (3D Stroma μTs) in a spinner flask bioreactor. Then, human colon cancer cells were dynamically seeded onto the 3D Stroma μTs to achieve the 3D CRC μTs. Morphological characterization of the 3D CRC μTs was performed to assess the presence of different complex macromolecular components that feature in vivo in the ECM. The results showed the 3D CRC μTs recapitulated the TME in terms of ECM remodeling, cell growth, and the activation of normal fibroblasts toward an activated phenotype. Then, the microtissues were assessed as a drug screening platform by evaluating the effect of 5-Fluorouracil (5-FU), curcumin-loaded nanoemulsions (CT-NE-Curc), and the combination of the two. When taken together, the results showed that our microtissues are promising in that they can help clarify complex cancer–ECM interactions and evaluate the efficacy of therapies. Moreover, they may be combined with tissue-on-chip technologies aimed at addressing further studies in cancer progression and drug discovery.https://www.mdpi.com/1422-0067/24/6/5678tumor microenvironment (TME)extracellular matrix (ECM)cancer associated fibroblasts (CAF)curcumin-loaded nanoemulsion (CT-NE-Curc)5-Fluorouracil (5-FU) |
| spellingShingle | Alessia La Rocca Vincenza De Gregorio Elena Lagreca Raffaele Vecchione Paolo Antonio Netti Giorgia Imparato Colorectal Cancer Bioengineered Microtissues as a Model to Replicate Tumor-ECM Crosstalk and Assess Drug Delivery Systems In Vitro International Journal of Molecular Sciences tumor microenvironment (TME) extracellular matrix (ECM) cancer associated fibroblasts (CAF) curcumin-loaded nanoemulsion (CT-NE-Curc) 5-Fluorouracil (5-FU) |
| title | Colorectal Cancer Bioengineered Microtissues as a Model to Replicate Tumor-ECM Crosstalk and Assess Drug Delivery Systems In Vitro |
| title_full | Colorectal Cancer Bioengineered Microtissues as a Model to Replicate Tumor-ECM Crosstalk and Assess Drug Delivery Systems In Vitro |
| title_fullStr | Colorectal Cancer Bioengineered Microtissues as a Model to Replicate Tumor-ECM Crosstalk and Assess Drug Delivery Systems In Vitro |
| title_full_unstemmed | Colorectal Cancer Bioengineered Microtissues as a Model to Replicate Tumor-ECM Crosstalk and Assess Drug Delivery Systems In Vitro |
| title_short | Colorectal Cancer Bioengineered Microtissues as a Model to Replicate Tumor-ECM Crosstalk and Assess Drug Delivery Systems In Vitro |
| title_sort | colorectal cancer bioengineered microtissues as a model to replicate tumor ecm crosstalk and assess drug delivery systems in vitro |
| topic | tumor microenvironment (TME) extracellular matrix (ECM) cancer associated fibroblasts (CAF) curcumin-loaded nanoemulsion (CT-NE-Curc) 5-Fluorouracil (5-FU) |
| url | https://www.mdpi.com/1422-0067/24/6/5678 |
| work_keys_str_mv | AT alessialarocca colorectalcancerbioengineeredmicrotissuesasamodeltoreplicatetumorecmcrosstalkandassessdrugdeliverysystemsinvitro AT vincenzadegregorio colorectalcancerbioengineeredmicrotissuesasamodeltoreplicatetumorecmcrosstalkandassessdrugdeliverysystemsinvitro AT elenalagreca colorectalcancerbioengineeredmicrotissuesasamodeltoreplicatetumorecmcrosstalkandassessdrugdeliverysystemsinvitro AT raffaelevecchione colorectalcancerbioengineeredmicrotissuesasamodeltoreplicatetumorecmcrosstalkandassessdrugdeliverysystemsinvitro AT paoloantonionetti colorectalcancerbioengineeredmicrotissuesasamodeltoreplicatetumorecmcrosstalkandassessdrugdeliverysystemsinvitro AT giorgiaimparato colorectalcancerbioengineeredmicrotissuesasamodeltoreplicatetumorecmcrosstalkandassessdrugdeliverysystemsinvitro |