R&D

Anti-inflammatory Effects of Oct4/Sox2-overexpressing Human Adipose Tissue-derived Mesenchymal Stem Cells

Background/Aim: The transcription factors Oct4
and Sox2 enhance the proliferation and pluripotency of
human adipose tissue-derived mesenchymal stem cells (hATMSCs);
however, the anti-inflammatory effects of Oct4- and
Sox2-overexpressing hAT-MSCs (Oct4/Sox2-hAT-MSCs) are
unclear. Here, we evaluated the anti-inflammatory effects of
Oct4/Sox2-hAT-MSCs in vitro and in vivo.

Accordingly, in this study, the anti-inflammatory effects
of lentivirus-transduced Oct4/Sox2-hAT-MSCs were
investigated by determining the expression of
inflammation-related cytokines in macrophage cell lines
treated with conditioned medium in vitro. In addition,
sickness scores (diarrhea, eye condition, activity and fur
condition) and survival rates were used to evaluate the antiinflammatory
effects of the engineered hAT-MSCs in a
mouse model.

Anti-tumor effect of adipose tissue derived-mesenchymal stem cells expressing interferon-β and treatment with cisplatin in a xenograft mouse model for canine melanoma

요약 : 
Adipose tissue-derived mesenchymal stem cells (AT-MSCs) are attractive cell-therapy vehicles for the delivery of anti-tumor molecules into the tumor microenvironment. The innate tropism of AT-MSCs for tumors has important implications for effective cellular delivery of anti-tumor molecules, including cytokines, interferon, and pro-drugs. The present study was designed to determine the possibility that the combination of stem cell-based gene therapy with low-dose cisplatin would improve therapeutic efficacy against canine melanoma. The IFN-b transduced canine AT-MSCs (cAT-MSC-IFN-b) inhibited the growth of LMeC canine melanoma cells in direct and indirect in vitro co-culture systems. In animal experiments using BALB/c nude mouse xenografts, which developed by injecting LMeC cells, the combination treatment of cAT-MSC-IFN-b and low-dose cisplatin significantly reduced tumor volume compared with the other treatment groups. Fluorescent microscopic analysis with a TUNEL (terminal deoxynucleotidyl transferase-mediated nick-end labeling) assay of tumor section provided evidence for homing of cAT-MSC-IFN-b to the tumor site and revealed that the combination treatment of cAT-MSC-IFN-b with low-dose cisplatin induced high levels of cell apoptosis. These findings may prove useful in further explorations of the application of these combined approaches to the treatment of malignant melanoma and other tumors

Anti-tumor effect of adipose tissue derived-mesenchymal stem cells expressing interferon-β and treatment with cisplatin in a xenograft mouse model for canine melanoma

Adipose tissue-derived mesenchymal stem cells (AT-MSCs) are attractive cell-therapy vehicles for the delivery of anti-tumor molecules into the tumor microenvironment. The innate tropism of AT-MSCs for tumors has important implications for effective cellular delivery of anti-tumor molecules, including cytokines, interferon, and pro-drugs. The present study was designed to determine the possibility that the combination of stem cell-based gene therapy with low-dose cisplatin would improve therapeutic efficacy against canine melanoma.

Anti-tumor effects of canine adipose tissue-derived mesenchymal stromal cell-based interferon-β gene therapy and cisplatin in a mouse melanoma model.

요약 :
Background aims. Adipose tissue (AT)-derived mesenchymal stromal cells (MSC) (AT-MSC) represent a novel tool for delivering therapeutic genes to tumor cells. Interferon (IFN)- β is a cytokine with pleiotropic cellular functions, including anti-proliferative, immunomodulatory and anti-angiogenic activities. The purpose of this study was to engineer canine AT-MSC (cAT-MSC) producing IFN- β and to evaluate the anti-tumor effect of cAT-MSC – IFN- β combined with cisplatin in mouse melanoma model. Methods. cAT-MSC engineered to express mouse IFN- β were generated using a lentiviral vector (cAT-MSC – IFN- β ) and the secreted IFN- β -induced inhibition of tumor cell growth and apoptosis on B16F10 cells was investigated in vitro prior to in vivo studies. Melanoma-bearing mouse was developed by injecting B16F10 cells subcutaneously into 6-week-old C57BL/6 mice. After 14 days, cisplatin (10 mg/kg) was injected intratumorally, and 3 days later the engineered cAT-MSC were injected subcutaneously every 3 days to death. Tumor volume and survival times were measured.
Results. The combination treatment of cAT-MSC – IFN- β with cisplatin was more effective in inhibiting the growth of melanoma and resulted in signifi cantly extended survival time than both an unengineered cAT-MSC – cisplatin combination group and a cisplatin-alone group. Interestingly, subcutaneously injected cAT-MSC – IFN- β were migrated to tumor sites. Conclusions. Our data suggest that canine AT-MSC could serve as a powerful cell-based delivery vehicle for releasing therapeutic proteins to tumor lesions. Maximal anti-tumor effects were seen when this therapy was combined with a DNAdamaging chemotherapeutic agent. This study demonstrates the possible applicability of AT-MSC-mediated IFN- β in treating canine and human cancer patients

Anti-wrinkle Effect of AdMSCs-CM in Photoaging Skin Model of Hairless Mice

요약 : 
The purpose of this study was to investigate the anti-wrinkle effect of adipose-derived mesenchymal stem cell-conditioned medium (AdMSCs-
CM) in a UVB irradiation-induced hairless mouse wrinkle model. Mice treated with AdMSCs-CM showed improvements in transepidermal water loss (TEWL), water capacity and erythema index of skin. The AdMSCs-CM treated mice showed reduced total wrinkle area, number, length and depth, as measured by gross observation and replica image analysis, and had a thinner epidermis and increased collagen and elastic fiber content, compared with the UV control group, as measured by histopathological examination. The activity of AdMSCs-CM was further confirmed by the reduction in MMP-3 mRNA expression and MMP-2, 9 protein activity in the skin of the AdMSCs CM treated animals. These results suggested that AdMSCs-CM may be effective in the treatment of wrinkles by protecting of the collagen from degradation induced by UV irradiation. Further studies about detailed mechanisms of action of AdMSCs-CM will be needed

Anti-Wrinkle Effects of Adipose Tissue-Derived Mesenchymal Stem Cells in a UV-Irradiated Hairless Mouse Model

요약 : 
The potential anti-wrinkle effects of adipose tissue-derived mesenchymal stem cells (AdMSCs) have recently been reported. In the present study, we demonstrated a protective effect of AdMSCs in a UV irradiationinduced
hairless mouse wrinkle model. Mice treated with AdMSCs showed improvements in skin erythema index, moisture capacity and transepidermal water loss. The AdMSC-treated mice showed reduced wrinkle area, as measured by gross observation and replica image analysis, and had a thinner epidermis and increased collagen and elastic fiber content, compared with the control group, as measured by histopathological examination. These results suggested that AdMSCs may be effective in the treatment of wrinkles. The activity of AdMSCs was further confirmed by the reduction in MMP-3 mRNA expression in the skin of the AdMSC treated animals, which suggests that AdMSCs can protect the collagen from degradation induced by UV irradiation. Further studies will investigate detailed mechanisms of action of AdMSCs, with particular focus on AdMSC-derived secretory factors