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Table 1 Heterotypic spheroid-based tumor models

From: Modelling the complex nature of the tumor microenvironment: 3D tumor spheroids as an evolving tool

3D culture model

Culture technique

Strengths

Weaknesses

References

Multicellular tumor spheroid

- Use of ultra-low adhesion substrates (e.g. polystyrene culture plates)

-Metabolic and proliferative gradients similar in vivo

-Clonality

-Easy Maintenance

-Ease of genetic manipulation

-Make use of FBS culture conditions

-Originated from cell lines

[102, 108]

Tissue derived tumor sphere

-Partial digestion of cancer tissues into small fragments that form in spherical structures

-Serum-free culture

-Native cell–cell contract is maintained

-Maintenance of histological characteristics

-Preservation of genetic phenotype and metastatic properties

-Deprived of stromal cells

[101, 110, 111]

Tumorsphere

-Mechanical and enzymatic dissociation of tumor samples into single cell suspensions

-Useful system to study CSC

-Serum-free culture conditions

-Lack to fully recapitulate the TME

-Require specific factors to favor stem cells growth

[113]

Organotypic multicellular spheroid

-Formed by excised tumors but without tissue digestion

-May be cryopreserved while maintaining their histological characteristics

-Highly similar to native tumor tissues

-High cellular heterogeneity

-Presence of vascular, immune and stromal fractions

-Dependent on a low-adhesion substrate (e.g. agarose) for spheroid formation

[114, 115, 117]

  1. Summary of spheroid-based tumor models including spheroid formation techniques, strengths and weaknesses