3D bioprinted mammary organoids and tumoroids in human mammary derived ECM hydrogels

Mollica, Peter A.; Booth-Creech, Elizabeth N.; Reid, John A.; Zamponi, Martina; Sullivan, Shea M.; Palmer, Xavier-Lewis; Sachs, Patrick C.; Bruno, Robert D.

doi:10.1016/j.actbio.2019.06.017

Cited by 138 publications

(115 citation statements)

References 37 publications

Supporting

Mentioning

109

Contrasting

Unclassified

Order By: Relevance

“…This study systemically examined the biological aspects of three types of native ECM hydrogels: TMG, Col I, and Matrigel. While Col I and Matrigel have been widely used in the biomedical field for various 2D or 3D cultures, normal native full ECM hydrogel derived from animal or human tissues [ 39 , 40 , 99 ], such as TMG, still requires better characterization for tissue- and disease-specific research applications. One of the mechanical properties of hydrogel important for tissue mimicry and cell biology studies is stiffness, as different tissues have quite different stiffness.…”

Section: Discussionmentioning

confidence: 99%

Distinct phenotypes of cancer cells on tissue matrix gel

Ruud

Hiscox

et al. 2020

Breast Cancer Res

View full text Add to dashboard Cite

Background: Breast cancer cells invading the connective tissues outside the mammary lobule or duct immerse in a reservoir of extracellular matrix (ECM) that is structurally and biochemically distinct from that of their site of origin. The ECM is a spatial network of matrix proteins, which not only provide physical support but also serve as bioactive ligands to the cells. It becomes evident that the dimensional, mechanical, structural, and biochemical properties of ECM are all essential mediators of many cellular functions. To better understand breast cancer development and cancer cell biology in native tissue environment, various tissue-mimicking culture models such as hydrogel have been developed. Collagen I (Col I) and Matrigel are the most common hydrogels used in cancer research and have opened opportunities for addressing biological questions beyond the two-dimensional (2D) cell cultures. Yet, it remains unclear whether these broadly used hydrogels can recapitulate the environmental properties of tissue ECM, and whether breast cancer cells grown on CoI I or Matrigel display similar phenotypes as they would on their native ECM. Methods: We investigated mammary epithelial cell phenotypes and metabolic profiles on animal breast ECMderived tissue matrix gel (TMG), Col I, and Matrigel. Atomic force microscopy (AFM), fluorescence microscopy, acini formation assay, differentiation experiments, spatial migration/invasion assays, proliferation assay, and nuclear magnetic resonance (NMR) spectroscopy were used to examine biological phenotypes and metabolic changes. Student's t test was applied for statistical analyses. Results: Our data showed that under a similar physiological stiffness, the three types of hydrogels exhibited distinct microstructures. Breast cancer cells grown on TMG displayed quite different morphologies, surface receptor expression, differentiation status, migration and invasion, and metabolic profiles compared to those cultured on Col I and Matrigel. Depleting lactate produced by glycolytic metabolism of cancer cells abolished the cell proliferation promoted by the non-tissue-specific hydrogel. Conclusion: The full ECM protein-based hydrogel system may serve as a biologically relevant model system to study tissue-and disease-specific pathological questions. This work provides insights into tissue matrix regulation of cancer cell biomarker expression and identification of novel therapeutic targets for the treatment of human cancers based on tissue-specific disease modeling.

show abstract

Section: Discussionmentioning

confidence: 99%

Distinct phenotypes of cancer cells on tissue matrix gel

Ruud

Hiscox

et al. 2020

Breast Cancer Res

View full text Add to dashboard Cite

show abstract

“…However, most studies demonstrated that 3D culture, especially Hangdrop technology, could enhance DPCs' regeneration in hair follicles after multiple passage times by the classical Wnt signalling pathway 3,32 . Such an observation could be attributed to the extracellular matrix (ECM), one of the critical components of cell growth that has a tremendous impact on the development of hair dermal papilla cells 33,34 . Nevertheless, the contributions from other pathways are uncertain.…”

Section: Discussionmentioning

confidence: 99%

RNA sequence analysis of dermal papilla cells’ regeneration in 3D culture

Lin

Yin

et al. 2020

J Cellular Molecular Medi

View full text Add to dashboard Cite

It is well known that dermal papilla cells (DPCs) are crucial for hair follicle growth and regeneration. However, dermal papilla cells in 2D culture could lose their ability of regeneration after several passage intervals. As opposed to DPCs in 2D culture, the DPCs in 3D culture could passage extensively. However, the molecular mechanisms of DPCs’ regeneration in 3D culture remain unclear. Accordingly, gene sequencing is recommended for the investigation of hair regeneration between 2D and 3D culture, the three groups were established including DPCs in passage 2 in 2D culture, DPCs in passage 8 in 2D culture and DPCs in passage 8 in 3D culture. The differentially expressed genes (DEGs) were identified using the Venn diagram of these three groups, which included 1642 known and 359 novel genes, respectively. A total of 1642 known genes were used for Gene Ontology (GO), Kyoto Gene, Genomic Encyclopedia (KEGG) pathway enrichment and protein‐protein interaction (PPI) analyses, respectively. The functions and pathways of DEGs were enriched in biological regulation, signal transduction and immune system, etc. The key module and the top 10 hub genes (IL1B, CXCL12, HGF, EGFR, APP, CCL2, PTGS2, MMP9, NGF and SPP1) were also identified using the Cytoscape application. Furthermore, the qRT‐PCR results of the three groups validated that the hub genes were crucial for hair growth. In conclusion, the ten identified hub genes and related pathways in the current study can be used to understand the molecular mechanism of hair growth, and those provided a possibility for hair regeneration.

show abstract

“…The authors were able to show that large organoids/tumoroids could be established in the mammary-derived hydrogel. 101 These studies show the great potential of decellularised scaffolds for the study of cancer and disease progression as well as the screening of new therapies. Idiopathic diseases such as inflammatory bowel diseases (e.g., Crohn's disease and ulcerative colitis) could also be modelled using decellularised matrices.…”

Section: Use Of Decellularised Scaffolds As 3d Ex Vivo Platformsmentioning

confidence: 99%

“…The authors concluded that the decellularised breast scaffold model would help to simulate the pathogenesis of breast cancer in vitro. 100 A last example reported by Mollica et al 101 described a novel mammary-specific culture combining a self-gelling hydrogel solely composed of decellularised rat or human breast tissue ECM with a 3D bioprinting platform. The authors were able to show that large organoids/tumoroids could be established in the mammary-derived hydrogel.…”

Section: Use Of Decellularised Scaffolds As 3d Ex Vivo Platformsmentioning

confidence: 99%

Decellularised scaffolds: just a framework? Current knowledge and future directions

et al. 2020

View full text Add to dashboard Cite

The use of decellularised matrices as scaffolds offers the advantage of great similarity with the tissue to be replaced. Moreover, decellularised tissues and organs can be repopulated with the patient’s own cells to produce bespoke therapies. Great progress has been made in research and development of decellularised scaffolds, and more recently, these materials are being used in exciting new areas like hydrogels and bioinks. However, much effort is still needed towards preserving the original extracellular matrix composition, especially its minor components, assessing its functionality and scaling up for large tissues and organs. Emphasis should also be placed on developing new decellularisation methods and establishing minimal criteria for assessing the success of the decellularisation process. The aim of this review is to critically review the existing literature on decellularised scaffolds, especially on the preparation of these matrices, and point out areas for improvement, finishing with alternative uses of decellularised scaffolds other than tissue and organ reconstruction. Such uses include three-dimensional ex vivo platforms for idiopathic diseases and cancer modelling.

show abstract

3D bioprinted mammary organoids and tumoroids in human mammary derived ECM hydrogels

Cited by 138 publications

References 37 publications

Distinct phenotypes of cancer cells on tissue matrix gel

Distinct phenotypes of cancer cells on tissue matrix gel

RNA sequence analysis of dermal papilla cells’ regeneration in 3D culture

Decellularised scaffolds: just a framework? Current knowledge and future directions

Contact Info

Product

Resources

About