Soluble factors secreted by human Wharton’s jelly mesenchymal stromal/stem cells exhibit therapeutic radioprotection: A mechanistic study with integrating network biology

BACKGROUND

Human Wharton’s jelly-derived mesenchymal stromal/stem cells (hWJ-MSCs) have gained considerable attention in their applications in cell-based therapy due to several advantages offered by them. Recently, we reported that hWJ-MSCs and their conditioned medium have significant therapeutic radioprotective potential. This finding raised an obvious question to identify unique features of hWJ-MSCs over other sources of stem cells for a better understanding of its radioprotective mechanism.

AIM

To understand the radioprotective mechanism of soluble factors secreted by hWJ-MSCs and identification of their unique genes.

METHODS

Propidium iodide staining, endogenous spleen colony-forming assay, and survival study were carried out for radioprotection studies. Homeostasis-driven proliferation assay was performed for in vivo lymphocyte proliferation. Analysis of RNAseq data was performed to find the unique genes of WJ-MSCs by comparing them with bone marrow mesenchymal stem cells, embryonic stem cells, and human fibroblasts. Gene enrichment analysis and protein-protein interaction network were used for pathway analysis.

RESULTS

Co-culture of irradiated murine splenic lymphocytes with WJ-MSCs offered significant radioprotection to lymphocytes. WJ-MSC transplantation increased the homeostasis-driven proliferation of the lymphocytes. Neutralization of WJ-MSC conditioned medium with granulocyte-colony stimulating factor antibody abolished therapeutic radioprotection. Transcriptome analysis showed that WJ-MSCs share several common genes with bone marrow MSCs and embryonic stem cells and express high levels of unique genes such as interleukin (IL)1-α, IL1-β, IL-6, CXCL3, CXCL5, CXCL8, CXCL2, CCL2, FLT-1, and IL-33. It was also observed that WJ-MSCs preferentially modulate several cellular pathways and processes that handle the repair and regeneration of damaged tissues compared to stem cells from other sources. Cytokine-based network analysis showed that most of the radiosensitive tissues have a more complex network for the elevated cytokines.

CONCLUSION

Systemic infusion of WJ-MSC conditioned media will have significant potential for treating accidental radiation exposed victims.

Key Words: Radioprotection, Mesenchymal stem cells, Wharton’s jelly-derived mesenchymal stromal/stem cells, Cytokines, Granulocyte-colony stimulating factor, Network biology

Core Tip: This study showed the potential role of cytokine granulocyte-colony stimulating factor in therapeutic radioprotection. Transcriptome analysis showed that Wharton’s jelly-derived mesenchymal stromal/stem cells (WJ-MSCs) have a unique set of genes compared to bone marrow MSCs and embryonic stem cells. WJ-MSCs secrete several cytokines that promote cellular pathways that handle tissue repair and regeneration.

• Citation: Maurya DK, Bandekar M, Sandur SK. Soluble factors secreted by human Wharton’s jelly mesenchymal stromal/stem cells exhibit therapeutic radioprotection: A mechanistic study with integrating network biology. World J Stem Cells 2022; 14(5): 347-361
• URL: https://www.wjgnet.com/1948-0210/full/v14/i5/347.htm
• DOI: https://dx.doi.org/10.4252/wjsc.v14.i5.347