Mesenchymal stem cell transplantation attenuates growth of chemotherapy treated oral squamous cell carcinoma in an animal model

Abstract

BackgroundRecent studies have demonstrated mesenchymal stem cell migration toward tumor locations. When applied locally, MSCs interact with the locally residing host cells. The mechanisms behind this are still unclear. We aimed to detect the possible action mechanisms of MSCs on the in vivo growth of primary human oral squamous cell carcinoma.MethodsIn mouse model of OSSC, chemotherapy with Cisplatin was done beginning from 9 day of tumor visualization. 3 weeks after tumor cell injection cultivated MSCs were administrated in tail vein or directly intra‐tumorally. Animals underwent surveillance and afterward were sacrificed. Tumor growth was measured. MSCs biodistribution was assessed with bioluminescent analysis. Tumor tissues were tested morphologically and immunohistochemically for angiogenesis, hypoxia status, and cell apoptosis.ResultsIn the group treated with Cisplatin in combination with mesenchymal stem cell injection, the average size of the tumor was 98.9 ± 7.65 mm3. In the experimental group, tumor tissues were less outlined and the presence of necrotic areas and connective tissue basal layers was detected. Immunohistochemical surveys with CD31 and anti‐carbonic anhydrase 9 demonstrated strongly developed micro‐vessel structures and small isles of hypoxia in the tumor tissues. TUNEL assay revealed in the same group that tumor tissues were mostly comprised of apoptotic cells. Viable cell communities presented as small isles.ConclusionThe study demonstrates that intra‐tumorally injected MSCs, combined with Cisplatin, leads to a minimal hypoxia status and increased apoptotic activity in tumor tissues, compared with the control group. This finding can be explained with better distribution of Cisplatin due to increased angiogenesis.

Safety and Homing of Human Dental Pulp Stromal Cells in Head and Neck Cancer

“…Similar to our results, they did not observe signi cant effects of hDPSC-derived conditioned medium (CM) on in vitro HNSCC proliferation and therapeutic sensitivity, and in vivo tumour growth, despite the increase in tumour VEGF secretion (45). Con icting results on the impact of other MSC subtypes on in vitro and in vivo HNC cell proliferation, survival, migration, invasion and therapeutic sensitivity have previously been described (46)(47)(48)(49)(50)(51)(52)(53). These effects (52,53).…”

“…Similarly, Zurmukhtashvili et al studied the tropism of 1 × 10 6 intravenously injected mouse BM-MSCs, three weeks after establishment of human oral squamous carcinoma (1 × 10 6 cells) in the buccal tissue of mice. BLI revealed concentration of the stem cells in the lungs, with no signal detected in the oral cavity (46). Although Zielske et al did show speci c in vivo tropism of intravenously injected hBM-MSCs towards head and neck UMSCC1 xenografts after 3, 8 and 14 days, the number of migrated cells was relatively low compared to HT-29 colon and MDA-MB-231 breast carcinomas.…”

“…With a diameter of 15 − 16 µm, DPSCs are slightly smaller than other MSC subtypes (17 − 18 µm) (71,72), but still outreach the size of the narrow lung capillary network (6 − 15 µm) (73,74). Therefore, systemic administration of MSCs is generally not recommended in cancer and other scienti c research elds, since the cell numbers reaching the desired target tissue are not su cient to induce therapeutic effects (46,70,75,76). Nevertheless, gradual migration of entrapped MSCs towards tumours has been demonstrated by other researchers and systemic administration could be useful in case of lung tumours or metastases (15,16,67,77).…”

Safety and Homing of Human Dental Pulp Stromal Cells in Head and Neck Cancer

“…Similar to our results, they did not observe signi cant effects of hDPSC-derived conditioned medium (CM) on in vitro HNSCC proliferation and therapeutic sensitivity, and in vivo tumour growth, despite the increase in tumour VEGF secretion(45). Con icting results on the impact of other MSC subtypes on in vitro and in vivo HNC cell proliferation, survival, migration, invasion and therapeutic sensitivity have previously been described(46)(47)(48)(49)(50)(51)(52)(53). These effects are mediated in a direct way via differentiation ofMSCs into malignant cells (54, 55), cancer-associated broblasts (CAFs) (56) and vascular-related cells (57, 58), or indirectly by (paracrine) interaction with immune cells (27, 59, 60), cancer stem cells (CSCs) (61-63), endothelial cells (24, 28, 64) and tumour cells (24, 30, 31, 65).…”

“…Intravenously injected DPSCs were mainly trapped in the small lung capillaries, which is a commonly described issue (70). (46,70,75,76). Nevertheless, gradual migration of entrapped MSCs towards tumours has been demonstrated by other researchers and systemic administration could be useful in case of lung tumours or metastases (15,16,67,77).…”