Page 299 - IJB-10-2

International Journal of Bioprinting Kidney hydrogel print for renal cancer model

IT1, P2RX6, SGK2, HIF1A-AS2, and ADIRF-AS1 were further modified for cell-laden bioprinting of different
significantly upregulated. RUNX1 is a transcription factor cells (like fibroblasts, immune cells, and endothelial cells)
that is critical for hematopoiesis and has been reported to for kidney cancer cell co-culture in the future.
be involved in diverse developmental processes, including
cell differentiation, proliferation, and apoptosis. RUNX1 5. Conclusion
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was upregulated in RCC tissues relative to normal In this study, we developed a 3D cell culture substrate for
tissues, and high RUNX1 expression leads to significantly ACHN cellular growth by mixing 10% GelMA with various
poorer clinical survival compared to patients with low concentrations of kidney dECM powders, including 1
expression. 56,57 Moreover, the inhibition of RUNX1 in wt%, 2 wt%, and 3 wt%, to mimic the ECM components
RCC cells can reduce cellular proliferation and viability. in the TME of RCC. The GelMA stability, mechanical
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P2RX6 belongs to the family of P2X receptors, which are properties, and printability were significantly improved
ATP-gated ion channels that mediate rapid and selective with the increase of dECM concentrations. Furthermore,
permeability to cations. It has been found that the RCC RNAseq results demonstrated that the 10% GelMA-2%
tissues express significantly higher levels of P2RX6, Kidney treatment could significantly enhance cellular
which modulate Ca -mediated p-ERK1/2/MMP9 growth and metastasis, a finding in concordance with
2+
signaling to increase RCC cell migration and invasion. the results of PCR and immunofluorescence staining of
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The SGKs participate in the regulation of diverse cellular EMT-related markers. In addition, we found that the 10%
processes, including osmoregulation, cell survival, sodium GelMA-2% Kidney treatment could significantly promote
homeostasis, cell proliferation, and invasion. The SGK the resistance of ACHN cells toward sunitinib, suggesting
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family comprises three members—SGK1, SGK2, and that the 10% GelMA-2% Kidney treatment is a potential
SGK3—with SGK2 being more highly expressed in the preclinical RCC model for in vitro drug screening and
liver, kidney, and brain. The upregulation of SGK2 has development.
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been shown to promote RCC progression by mediating
the phosphorylation of ERK1/2/AKT/PKB, indicating Acknowledgments
that SGK2 could be a potential prognostic marker for
RCC patients. Furthermore, KEGG enrichment analysis None.
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showed that ACHN cells were enriched in the VEGF,
HIF-1, and TGF-beta signaling pathways, all of which Funding
were significantly correlated with RCC progression and This study was partly funded by the National Natural
chemotherapy resistance. 62,63 Science Foundation of China (Grant No. 12202387), the
3D bioprinting technique has been widely applied in the Natural Science Foundation of Zhejiang Province (Grant
development of tumor models for investigation purposes. No. BY23H180015), the Natural Science Foundation of
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For instance, our group has successfully created prostate Ningbo (Grant Nos. 2022J216, 2022J212), the Foundation
cancer models for the investigation of cell–cell interaction of Ningbo Science and Technology Bureau (Grant No.
and drug resistance, and also summarized the application 2023Z193), Ningbo Medical Science and Technology
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of 3D bioprinting in urological diseases. Other research Program (Grant No. 2020Y73), and the Zhejiang Medical
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groups have also demonstrated that 3D-bioprinted tumor Science and Technology Project (Grant No. 2020KY825).
models for cholangiocarcinoma and liver cancer provide
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platforms for more accurately assessing drug effectiveness. Conflict of interest
The cancer cells in 3D-bioprinted tumor model were The authors declare that they have no financial and
commonly laden in thin filaments with grid structure, personal relationships with other people or organizations
and all cells were in homogeneous contact with culture that can inappropriately influence our work, and there is
media, a growth pattern different from that in mold-casted no professional or other personal interest of any nature or
tumor models (which were commonly solid cylinder or kind in any product, service, and/or company that could
cube-like), where cells at varying locations in the tumor be construed as influencing the position of the authors in
model manifest different cellular behavior. The TME this paper.
is a complicated structure, containing growth factors,
extracellular matrix, and non-cancer cells. Fortunately, 3D Author contributions
bioprinting is capable of simulating the TME architecture Conceptualization: Kailei Xu
in a co-culture model by printing various types of cells in Formal analysis: Miaoben Wu, Hangyu Zhou, Jingying Hu,
precise location. The bioink and nephron model developed Zonghuan Wang
in this study provide potential platform that could be

Volume 10 Issue 2 (2024) 291 doi: 10.36922/ijb.1413