Doyle Kathleen, Sutter Maria, Rodriguez Monica, Hassan Abd-Elrahman, Kumar Priyadarsini, Brown Erin
Department of Surgery, University of California-Davis, Sacramento, CA, USA.
Center for Surgical Bioengineering, Department of Surgery, University of California-Davis, Sacramento, CA, USA.
J Pediatr Surg. 2024 Aug;59(8):1582-1590. doi: 10.1016/j.jpedsurg.2024.02.014. Epub 2024 Feb 26.
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.
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.
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).
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.
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Original Research.
神经母细胞瘤是一种常见的儿科恶性肿瘤，高危疾病患者的生存率较低。间充质基质细胞（MSC）具有天然的肿瘤归巢特性，使其能够作为细胞递送载体，但MSC对肿瘤生长的影响存在差异。我们比较了胎盘间充质基质细胞（PMSC）和骨髓来源的间充质基质细胞（BM-MSC）在体外对神经母细胞瘤（NB）细胞增殖的影响。
间接共培养评估了18种MSC（早孕期PMSC（n = 9）、足月PMSC（n = 5）、BM-MSC（n = 4））对三种高危NB细胞系（NB1643、SH-SY5Y和CHLA90）的增殖作用。对照组为仅在培养基中培养的NB细胞。使用MTS试验评估增殖情况，并通过相对于对照组的变化倍数（fc）进行测量。PMSC按神经保护作用分为亚组：强（n = 7）、中（n = 3）、弱（n = 4）。评估了MSC类型、PMSC神经保护作用和PMSC胎龄与NB细胞增殖之间的关系。
NB细胞增殖在MSC组之间存在差异。BM-MSC的增殖作用低于PMSC（fc 1.18对1.44，p < 0.001）。胎龄和神经保护作用均未显著预测增殖程度。MSC的增殖作用在NB细胞系之间有所不同。与NB1643（fc 1.33）和SH-SY5Y（fc 1.20）相比，BM-MSC对CHLA90的作用较小（fc 1.01）。仅NB1643显示早孕期和足月PMSC之间存在差异（p = 0.04）。
MSC对NB细胞增殖的影响因MSC来源和NB细胞系而异。BM-MSC的增殖作用低于大多数PMSC。MSC神经保护作用与增殖无关。对MSC促增殖机制的深入了解可能为选择最适合作为药物递送载体的细胞提供有价值的见解。
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原创研究。
