目前很多研究利用間質幹細胞具有腫瘤趨向性，作為裝載抗癌藥物的細胞載體以治療癌症。然而，間質幹細胞在腫瘤發展的影響卻具有很多爭議性，並可能因此阻礙間質幹細胞臨床癌症治療的發展。為了確保此細胞治療的安全性，必須了解抗癌間質幹細胞與促癌間質幹細胞在癌症發展過程中之間的差異性。
首先，我們發現葡聚醣包覆的氧化鐵奈米粒子(簡稱為葡聚醣氧化鐵奈米粒子)不但可以強化抗癌間質幹細胞的抗癌效果，而且可以逆轉促癌間質幹細胞促進癌症的影響，這表示葡聚醣氧化鐵奈米粒子可以在活體內將促癌間質幹細胞轉化成為抗癌間質幹細胞。在體外的細胞實驗結果發現：此奈米粒子(1)可以抑制癌症細胞群落的形成、(2)促進間質幹細胞表面的激素受體表現以與癌細胞競爭結合更多癌細胞分泌的細胞激素、(3)可以抑制促癌間質幹細胞分化成癌症相關的纖維母細胞及內皮細胞，也(4)能抑制促癌間質幹細胞對宿主內生性前驅細胞分化成癌症相關的纖維母細胞及內皮細胞的能力。
進一步根據微陣列篩查結果，相較於促癌間質幹細胞，我們發現Interferon-induced protein 44-like (IFI44L)在抗癌間質細胞會大量表現；而且在葡聚醣氧化鐵奈米粒子轉化的促癌間質幹細胞(已轉變成抗癌間質幹細胞，又稱後天的抗癌間質幹細胞)，IFI44L的表現量明顯的被誘導。在活體動物實驗中，利用小分子核糖核酸干擾的技術降低抗癌間質幹細胞IFI44L的基因表現，即能降低抗癌間質幹細胞的抗癌效果；相反的，在促癌間質幹細胞大量表現IFI44L，促癌間質幹細胞則會轉變成抗癌間質幹細胞，抑制癌症的生長。在細胞實驗結果中，我們發現間質幹細胞可分泌IFI44L至細胞外。在促癌間質幹細胞大量表現分泌的IFI44L，可抑制內皮前驅細胞的管柱形成的能力；反之，在抗癌間質幹細胞抑制IFI44L的表現分泌，則會促進內皮前驅細胞的管柱形成的能力。根據這些功能增加及功能喪失的實驗結果，我們認為間質幹細胞分泌的IFI44L具調控血管新生的影響。另一方面，在內皮前驅細胞大量表現IFI44L，亦可直接抑制其管柱形成；相反的，在內皮前驅細胞抑制IFI44L的表現，會增加管柱形成的現象。這表示IFI44L可能直接影響內皮前驅細胞的血管新生的功能。整體而言，我們證實IFI44L 不只是在間質幹細胞的抗癌能力扮演重要的角色，IFI44L可作為細胞標記來決定間質幹細胞究竟是癌症細胞的朋友(促癌間質幹細胞)或是敵人(抗癌間質幹細胞)。

Mesenchymal stem cells or multipotent mesenchymal stromal cells (MSCs) with the tumor tropism have shown promise as a cellular deliverer of anticancer agents for cancer therapy. However, the conflicting outcomes in the studies of MSCs on tumor progression may impede the clinical application of MSC-based cancer therapy. In order to ensure pertinent MSC-based cancer therapy, it is essential to further distinguish the molecular foundations for the discrepancies of the impacts on tumor progression between antitumor MSCs (aT-MSCs) and protumor MSCs (pT-MSCs).
First, we show that dextran-coated iron oxide nanoparticles (dex-IO NPs) can not only increase the antitumor effect of native aT-MSCs but also reverse the protumor effect of native pT-MSCs and hence dex-IO NPs turn pT-MSCs into aT-MSCs in vivo. The in vitro finding that dex-IO NPs (1) can inhibit the colony formation of cancer cells, (2) induce cytokine receptor expression to competitively capture the tumorous cytokine, (3) impair pT-MSCs to differentiate to cancer-mediated fibroblast cells and endothelial-like cells and (4) inhibit pT-MSCs to promote the intrinsic tumor-associated precursors differentiate to fibroblasts and endothelial-like cells.
Furthermore, microarray screen analysis revealed that interferon-induced protein 44-like (IFI44L) was highly expressed in innate aT-MSCs and markedly induced in acquired aT-MSCs from dex-IO NP-transformed pT-MSCs, compared with innate pT-MSCs. IFI44L loss of function in aT-MSCs attenuated their antitumor effects; conversely, the transduction of IFI44L in pT-MSCs blocked their protumor effects in vivo. In vitro, we showed that overexpressed IFI44L in pT-MSCs could be secreted into media to attenuate the tube formation of human endothelial progenitor cells. In contrast, silence of IFI44L in aT-MSCs would result in the decrease of IFI44L in aT-MSCs-derived media. The tube formation of human endothelial progenitor cells in the media from IFI44L-silenced aT-MSCs-derived media would be enhanced than the media from aT-MSCs-derived media. Overall, the gain- and loss-of-function experiments confirmed the secreted IFI44L in MSCs-derived media can mediate the angiogenesis. On the other hand, silencing IFI44L in human endothelial progenitor cells significantly promoted their tube formation ability and overexpression of IFI44L in human endothelial progenitor cells significantly reduced their tube formation ability, suggesting IFI44L may directly affect the angiogenesis in human endothelial progenitor cells. Our results not only identified a central role for IFI44L in antitumor effects of MSCs but also suggested that IFI44L could be a marker for determining MSCs to be friends (protumor MSCs) or enemies (antitumor MSCs) of cancer cells.

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