Proliferative Effects of Mesenchymal Stromal Cells on Neuroblastoma Cell Lines: Are They Tumor Promoting or Tumor Inhibiting?
Publication Year:
2024
PubMed ID:
38490883
Funding Grants:
Public Summary:
Neuroblastoma is one of the more common cancers found in young children, and when it's classified as "high-risk," survival rates remain disappointingly low. Researchers have been exploring a creative treatment strategy: using mesenchymal stromal cells (MSCs) as delivery vehicles to carry cancer-fighting drugs directly to tumors, since MSCs have a natural tendency to migrate toward tumor tissue. But there's a catch. Past research has shown that MSCs don't always behave the same way once they reach a tumor — in some cases, they might actually help the cancer cells grow rather than just delivering a therapeutic payload. Before using MSCs as drug carriers becomes a viable treatment strategy, scientists need to understand this risk clearly.
This study focused on comparing two possible sources of MSCs: cells derived from placental tissue (PMSCs) and cells derived from bone marrow (BM-MSCs). The researchers grew each type of MSC in the same lab dish environment as three different high-risk neuroblastoma cell lines, without letting the cells physically touch, so they could measure whether the mere presence of MSCs nearby caused the cancer cells to multiply faster than they would on their own.
They also took a closer look at the placental MSCs specifically, since these cells are already known for a helpful property called "neuroprotection" — the ability to protect and support nerve cells. The researchers wanted to know whether placental MSCs with strong neuroprotective properties were more or less likely to also encourage cancer cell growth, and whether the placenta's stage of development (early versus full-term pregnancy) made a difference.
The results showed clear differences between the two MSC sources. Overall, bone marrow-derived MSCs caused less cancer cell growth compared to most placental MSCs. However, neither how strongly a placental MSC supported nerve health, nor how far along the pregnancy was when the placental tissue was collected, reliably predicted how much a given batch of cells would boost cancer cell growth. The effects also weren't consistent across the different neuroblastoma cell lines tested — bone marrow MSCs had almost no growth-promoting effect on one particular cell line, but a more noticeable effect on the other two.
Taken together, these findings reveal an important nuance: not all MSCs are equally safe to use as drug-delivery vehicles, and their effects can depend on both where the cells come from and which specific cancer cells they're paired with. Bone marrow-derived MSCs appeared to be somewhat safer overall in this study, showing less tendency to accidentally accelerate cancer cell growth compared to placental MSCs.
This research doesn't yet answer why some MSCs promote tumor growth more than others, but it highlights the importance of carefully screening and selecting the right cell source before using MSCs in cancer therapy. A better understanding of the underlying biological mechanisms driving this growth-promoting effect could ultimately help researchers identify or engineer the safest, most effective MSCs for delivering treatment directly to childhood tumors like neuroblastoma.
Scientific Abstract:
BACKGROUND: Neuroblastoma is a common pediatric malignancy with poor survival for high-risk disease. Mesenchymal stromal cells (MSCs) have innate tumor-homing properties, enabling them to serve as a cellular delivery vehicle, but MSCs have demonstrated variable effects on tumor growth. We compared how placental MSCs (PMSCs) and bone marrow-derived MSCs (BM-MSCs) affect proliferation of neuroblastoma (NB) cells in vitro. METHODS: Indirect co-culture assessed proliferative effects of 18 MSCs (early-gestation PMSCs (n = 9), term PMSCs (n = 5), BM-MSCs (n = 4) on three high-risk NB cell lines (NB1643, SH-SY5Y, and CHLA90). Controls were NB cells cultured in media alone. Proliferation was assessed using MTS assay and measured by fold change (fc) over controls. PMSCs were sub-grouped by neuroprotective effect: strong (n = 7), intermediate (n = 3), and weak (n = 4). The relationship between MSC type, PMSC neuroprotection, and PMSC gestational age on NB cell proliferation was assessed. RESULTS: NB cell proliferation varied between MSC groups. BM-MSCs demonstrated lower proliferative effects than PMSCs (fc 1.18 vs 1.44, p < 0.001). Neither gestational age nor neuroprotection significantly predicted degree of proliferation. Proliferative effects of MSCs varied among NB cell lines. BM-MSCs had less effect on CHLA90 (fc 1.01) compared to NB1643 (fc 1.33) and SH-SY5Y (fc 1.20). Only NB1643 showed a difference between early and term PMSCs (p = 0.04). CONCLUSION: Effects of MSCs on NB cell proliferation vary by MSC source and NB cell line. BM-MSCs demonstrated lower proliferative effects than most PMSCs. MSC neuroprotection was not correlated with proliferation. Improved understanding of MSC proliferation-promoting mechanisms may provide valuable insight into selection of cells best suited as drug delivery vehicles. LEVEL OF EVIDENCE: N/A. TYPE OF STUDY: Original Research.