The effects of hyperthermia on the immunomodulatory properties of human umbilical cord vein mesenchymal stem cells (MSCs)

Hesami, Shilan; Mohammadi, Mehdi; Rezaee, Mohammad Ali; Jalili, Ali; Rahmani, Mohammadreza

doi:10.1080/02656736.2017.1309576

Cited by 7 publications

(6 citation statements)

References 31 publications

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“…We found >95% of cells to be viable, although data were not saved in images. In addition, literature reports have confirmed our observation that MSCs, including AMMSCs, do not undergo serious structural damage or molecular changes during or post-hyperthermia [11,13,36]. Another study has demonstrated that after receiving heat shock pretreatment at 42°C for 1 h, bone marrow MSCs display their lowest apoptotic rate, owing to the elevated expression of heat shock proteins (HSPs) HSP70 and HSP90 inside the cells [37].…”

Section: Growth Characterization Of Tumor Spheroids: Co-culture Accelerated Tumor Growthsupporting

confidence: 69%

Indirect co-culture of lung carcinoma cells with hyperthermia-treated mesenchymal stem cells influences tumor spheroid growth in a collagen-based 3-dimensional microfluidic model

et al. 2021

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Background: Mesenchymal stem cells (MSCs) have paradoxically been reported to exert either pro-or antitumor effects in vitro. Hyperthermia, in combination with chemotherapy, has tumor-inhibiting effects; however, its role, together with MSCs, so far is not well understood. Furthermore, a lot of research is conducted using conventional 2-dimensional in vitro models that do not mimic the actual tumor microenvironment. Aim: In light of this fact, an indirect method of co-culturing human amniotic membrane-derived MSCs (AMMSCs) with collagen-encapsulated human lung carcinoma cells (A549) was performed using a 3-dimensional (3D) tumor-on-chip device. Methods: The conditioned medium of AMMSCs (AMMSC-CM) or heat-treated AMMSCs (heat-AMMSC-CM) was utilized to create indirect co-culture conditions. Tumor spheroid growth characterization, immunocytochemistry and cytotoxicity assays, and anti-cancer peptide (P1) screening were performed to determine the effects of the conditioned medium. Results: The A549 cells cultured inside the 3D microfluidic chip developed into multicellular tumor spheroids over five days of culture. The AMMSC-CM, contrary to previous reports claiming its tumor-inhibiting potential, led to significant proliferation of tumor spheroids. Heat-AMMSC-CM led to reductions in both spheroid diameter and cell proliferation. The medium containing the P1 peptide was found to be the least cytotoxic to tumor spheroids in co-culture compared with the monoculture and heat-co-culture groups. Conclusions: Hyperthermia, in combination with the anticancer peptide, exhibited highest cytotoxic effects. This study highlights the growing importance of 3D microfluidic tumor models for testing stem-cell-based and other anti-cancer therapies.

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Section: Growth Characterization Of Tumor Spheroids: Co-culture Accelerated Tumor Growthsupporting

confidence: 69%

Indirect co-culture of lung carcinoma cells with hyperthermia-treated mesenchymal stem cells influences tumor spheroid growth in a collagen-based 3-dimensional microfluidic model

et al. 2021

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“…Enlarged temperature enhanced the proliferation of UCV-MSC cocultured with mononuclear cells of the peripheral blood as well as expression of IL-10, TGF- β 1, and FOXP3 mRNAs. It had no effect on IL-17A and IFN- γ secretion and reduced CXCL12 [24]. In our experiments, sublethal temperature has induced preliminary senescence [25] which is a mechanism of maintenance of MSC genetic stability by excluding damaged cells from the proliferation pool.…”

Section: Introductionmentioning

confidence: 96%

Quiescent Human Mesenchymal Stem Cells Are More Resistant to Heat Stress than Cycling Cells

Алексеенко

Шилина

Lyublinskaya

et al. 2018

Stem Cells International

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Quiescence is the prevailing state of many cell types under homeostatic conditions. Yet, surprisingly, little is known about how quiescent cells respond to environmental challenges. The aim of the present study is to compare stress responses of cycling and quiescent mesenchymal stem cells (MSC). Human endometrial mesenchymal cells (eMSС) were employed as adult stem cells. eMSC quiescence was modeled by serum starvation. Sublethal heat shock (HS) was used as a stress factor. Both quiescent and cycling cells were heated at 45°C for 30 min and then returned to standard culture conditions for their recovery. HS response was monitored by DNA damage response, stress-induced premature senescence (SIPS), cell proliferation activity, and oxidative metabolism. It has been found that quiescent cells repair DNA more rapidly, resume proliferation, and undergo SIPS less than proliferating cells. HS-enforced ROS production in heated cycling cells was accompanied with increased expression of genes regulating redox-active proteins. Quiescent cells exposed to HS did not intensify the ROS production, and genes involved in antioxidant defense were mostly silent. Altogether, the results have shown that quiescent cells are more resistant to heat stress than cycling cells. Next-generation sequencing (NGS) demonstrates that HS-survived cells retain differentiation capacity and do not exhibit signs of spontaneous transformation.

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“…On the other hand, tumor-associated MSCs were observed to protect ovarian cancer from hyperthermia via the CXCL12/ CXCR4-axis [19]. Furthermore, heat-exposed MSCs exhibited reduced inhibitory effects on lymphocytes compared to untreated MSCs [20]. Besides the stem cells' potential role in tumor protection after hyperthermia, MSCs have shown to play a role in the regeneration of hyperthermia-treated normal tissues.…”

Section: Introductionmentioning

confidence: 99%

Multipotent mesenchymal stromal cells are sensitive to thermic stress – potential implications for therapeutic hyperthermia

Rühle

Thomsen

Saffrich

et al. 2020

International Journal of Hyperthermia

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Purpose: Hyperthermia demonstrated clinical efficacy in multimodal cancer treatment. Multipotent mesenchymal stromal cells (MSCs) as part of the tumor-supporting stroma modulate tumor response and tissue regeneration after hyperthermia. We aimed to investigate the effects of hyperthermia on the survival, stem cell characteristics and heat shock expression of human MSCs. Materials and methods: Human MSCs and normal human dermal fibroblasts (NHDFs) were exposed to temperatures between 37 C and 44 C for 60 min, and hyperthermic sensitivity was examined by clonogenicity, proliferation and viability assays. The influence of 42 C hyperthermia on the MSCs' adhesion potential, migratory capacity, surface marker expression and multi-lineage differentiation capability was investigated. Cell cycle distribution, apoptosis and senescence after 42 C hyperthermia were determined by flow cytometry and b-galactosidase staining. Heat shock protein expression was determined by Western Blots. Results: MSCs exhibited decreased clonogenic survival after 40 C and 42 C hyperthermia compared to NHDFs, while proliferative activity and viability were comparable after hyperthermia up to 44 C. MSC adhesion was reduced after 42 C hyperthermia, while the characteristic surface marker expression and the migratory ability remained unaffected in 42 C hyperthermia-exposed MSCs. 42 C hyperthermia diminished the adipogenic differential potential of all tested MSC samples. A pronounced G2/ M arrest was found after 42 C hyperthermia and was associated with increased apoptosis and senescence levels in MSCs. MSCs exhibited slightly lower heat shock protein levels compared to NHDFs. Conclusion: Human MSCs exhibit a thermosensitive phenotype which reduced the multipotent cells' regenerative abilities, resulting in impaired tissue regeneration after hyperthermia treatment or thermal injuries. On the other hand, tumor-associated MSCs may be efficiently targeted by hyperthermia treatment.

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The effects of hyperthermia on the immunomodulatory properties of human umbilical cord vein mesenchymal stem cells (MSCs)

Abstract: Hyperthermia increases cell proliferation of the peripheral blood mononuclear cells and modifies the cytokine profile in the presence of UCV-MSCs.

Cited by 7 publications

References 31 publications

Indirect co-culture of lung carcinoma cells with hyperthermia-treated mesenchymal stem cells influences tumor spheroid growth in a collagen-based 3-dimensional microfluidic model

Indirect co-culture of lung carcinoma cells with hyperthermia-treated mesenchymal stem cells influences tumor spheroid growth in a collagen-based 3-dimensional microfluidic model

Quiescent Human Mesenchymal Stem Cells Are More Resistant to Heat Stress than Cycling Cells

Multipotent mesenchymal stromal cells are sensitive to thermic stress – potential implications for therapeutic hyperthermia

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