Efficiency of GrowDex<sup>®</sup> nanofibrillar cellulosic hydrogel when generating homotypic and heterotypic 3D tumor spheroids

Perumalsamy Balaji; Anbazhagan Murugadas; Lauri Paasonen; Sellathamby Shanmugaapriya; Mohammad A. Akbarsha; Perumalsamy Balaji; Anbazhagan Murugadas; Lauri Paasonen; Sellathamby Shanmugaapriya; Mohammad A. Akbarsha

doi:10.3934/biophy.2022019

AIMS Biophysics

2022, Volume 9, Issue 3: 221-234. doi: 10.3934/biophy.2022019

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Efficiency of GrowDex^® nanofibrillar cellulosic hydrogel when generating homotypic and heterotypic 3D tumor spheroids

1.
Department of Biomedical Science, Bharathidasan University, Tiruchirapalli 620024, India [Present address: Department of Biochemistry, University of Nebraska Medical Center, Omaha, Nebraska, USA]
2.
Department of Environmental Biotechnology, Bharathidasan University, Tiruchirapalli 620024, India [Present address: Department of Pediatrics, Emory University School of Medicine & Children's Healthcare of Atlanta, Atlanta, Georgia, USA]
3.
UPM Biomedicals, Helsinki, Finland
4.
Mahatma Gandhi-Doerenkamp Centre for Alternatives, Bharathidasan University, Tiruchirappalli 620024, India
5.
National College (Autonomous), Tiruchirappalli 620001, India

Received: 26 June 2022 Revised: 20 July 2022 Accepted: 26 July 2022 Published: 05 August 2022

In recent times, homotypic and heterotypic 3D tumor spheroid (HTS) models have been receiving increasing attention and come to be widely employed in preclinical studies. The present study is focused on the generation of homotypic (A549 and MDA-MB-231, separately) and heterotypic (A549 + NIH/3T3; MDA-MB-231 + NIH/3T3) 3D tumor spheroids by using GrowDex^® nanofibrillar cellulosic (NFC) hydrogel as the scaffold. Light microscopic observations and F-actin staining confirmed the formation of spheroids. The proliferation efficiency indicated an expansion of cell population and an increase in spheroid size over time. The distribution, interaction pattern and influence of fibroblasts on the epithelial cell types were observed in terms of the size and shape of the HTS against homo-spheroids. An interesting observation was that, with an increase in the size of HTSs, many more fibroblast cells were found to occupy the core region, which, perhaps, was due to the faster growth of tumor cells over normal cells. Thus, normal and tumor cells, especially with origins from two different species, can be cultured together in 3D format, and this can potentially enhance our knowledge of tumor microenvironments and cell-cell interaction. These spheroids could be used to improve microphysiological systems for drug discovery and to better understand the tumor microenvironment.
- 3D culture,
- multicellular tumor spheroids,
- GrowDex^®,
- hydrogel,
- heterotypic spheroids
Citation: Perumalsamy Balaji, Anbazhagan Murugadas, Lauri Paasonen, Sellathamby Shanmugaapriya, Mohammad A. Akbarsha. Efficiency of GrowDex® nanofibrillar cellulosic hydrogel when generating homotypic and heterotypic 3D tumor spheroids[J]. AIMS Biophysics, 2022, 9(3): 221-234. doi: 10.3934/biophy.2022019

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Abstract

In recent times, homotypic and heterotypic 3D tumor spheroid (HTS) models have been receiving increasing attention and come to be widely employed in preclinical studies. The present study is focused on the generation of homotypic (A549 and MDA-MB-231, separately) and heterotypic (A549 + NIH/3T3; MDA-MB-231 + NIH/3T3) 3D tumor spheroids by using GrowDex^® nanofibrillar cellulosic (NFC) hydrogel as the scaffold. Light microscopic observations and F-actin staining confirmed the formation of spheroids. The proliferation efficiency indicated an expansion of cell population and an increase in spheroid size over time. The distribution, interaction pattern and influence of fibroblasts on the epithelial cell types were observed in terms of the size and shape of the HTS against homo-spheroids. An interesting observation was that, with an increase in the size of HTSs, many more fibroblast cells were found to occupy the core region, which, perhaps, was due to the faster growth of tumor cells over normal cells. Thus, normal and tumor cells, especially with origins from two different species, can be cultured together in 3D format, and this can potentially enhance our knowledge of tumor microenvironments and cell-cell interaction. These spheroids could be used to improve microphysiological systems for drug discovery and to better understand the tumor microenvironment.

Acknowledgments

This work was carried out at Mahatma Gandhi-Doerenkamp Center for Alternatives to the Use of Animals in Life Science Education, Bharathidasan University, Tiruchirappalli, which was established and is funded by the Doerenkamp-Zbinden Foundation, Switzerland. We thank UPM Biomedicals, Helsinki, Finland, for providing the GrowDex^®NFC hydrogel.

Conflict of interest

All authors declare no conflicts of interest regarding this study.

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