Adipose‑derived stem cell‑mediated alphastatin targeting delivery system inhibits angiogenesis and tumor growth in glioma

Liang,Chen; Wei,Ting; Zhang,Ting; Niu,Chen

doi:10.3892/mmr.2023.13102

Adipose‑derived stem cell‑mediated alphastatin targeting delivery system inhibits angiogenesis and tumor growth in glioma

Authors:
- Chen Liang
- Ting Wei
- Ting Zhang
- Chen Niu
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Affiliations: Department of Neurosurgery, First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, Shaanxi 710061 P.R. China, Department of Ophthalmology, First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, Shaanxi 710061 P.R. China, Department of Otorhinolaryngology‑Head and Neck Surgery, First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, Shaanxi 710061 P.R. China, Positron Emission Tomography/Computed Tomography Center, First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, Shaanxi 710061 P.R. China
Published online on: September 26, 2023 https://doi.org/10.3892/mmr.2023.13102
Article Number: 215
Copyright: © Liang et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

Malignant glioma is a highly vascularized tumor. Therefore, inhibition of angiogenesis is an effective treatment strategy for it. Alphastatin is a 24‑amino acid peptide that has been demonstrated to inhibit glioma angiogenesis and tumor growth. Adipose‑derived stem cells (ADSCs) are considered an ideal targeted drug delivery system for glioma therapy due to their targeted tropism for cancer and the intrinsic attribute of autologous transplantation. The aim of the present study was to construct an ADSC‑mediated alphastatin targeted delivery system and investigate its effects on angiogenesis in glioma. The sequence encoding the human neurotrophin‑4 signal peptide and alphastatin fusion gene fragment was transferred into ADSCs using a lentiviral vector to construct the ADSC‑mediated alphastatin targeted delivery system (Al‑ADSCs). Flow cytometry was used to detect the stem cell surface markers of Al‑ADSCs. Western blot analysis and ELISA were used to detect the expression and secretion of alphastatin peptide in Al‑ADSCs. Cell migration assay was used to detect the tendency of Al‑ADSCs to target CD133⁺ glioma stem cells (GSCs). The effects of Al‑ADSCs on angiogenesis in vitro were detected by tube formation assay. A Cell Counting Kit‑8 assay was used to detect the effects of Al‑ADSCs on endothelial cell (EC) proliferation. Wound healing assay was used to examine the effects of Al‑ADSCs on EC migration. Intracranial xenograft models were constructed and in vivo fluorescence imaging was used to examine the effects of Al‑ADSCs on glioma growth. Fluorescence microscopy was used to detect the distribution of Al‑ADSCs in glioma tissue and CD133 immunofluorescence staining was used to detect the effects of Al‑ADSCs on GSCs in glioma tissue. The results revealed that ADSCs exhibited more marked tropism to GSCs than to other types of cells (P<0.01). Al‑ADSCs maintained the surface markers of ADSCs and there was no significant difference between the ADSCs and Al‑ADSCs regarding tropism to GSCs (P=0.639 for GSCs‑SHG44 cells; and P=0.386 for GSCs‑U87 cells). Al‑ADSCs were able to successfully secrete and express alphastatin peptide and inhibited EC‑mediated angiogenesis (P<0.01) and EC migration (P<0.01) and proliferation (P<0.01) in vitro. In vivo, Al‑ADSCs were detected in glioma tissue and were able to inhibit tumor growth. In addition, the Al‑ADSCs reduced the number of GSCs and microvascular density (P<0.01) in the tumors. Overall, the results of the present study indicated that the Al‑ADSCs were able to target glioma tissue and inhibit glioma angiogenesis and tumor growth. This anti‑angiogenic targeted therapy system may provide a new strategy for the treatment of glioma.

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