Biomedicines (Feb 2023)

Mesenchymal Stem Cells Genetically Modified by Lentivirus-Express Soluble TRAIL and Interleukin-12 Inhibit Growth and Reduced Metastasis-Relate Changes in Lymphoma Mice Model

  • Adriana G. Quiroz-Reyes,
  • Carlos A. Gonzalez-Villarreal,
  • Alberto Y. Limon-Flores,
  • Paulina Delgado-Gonzalez,
  • Herminia G. Martinez-Rodriguez,
  • Salvador L. Said-Fernandez,
  • Adolfo Soto-Dominguez,
  • Ana M. Rivas-Estilla,
  • Jose F. Islas,
  • Juan F. Molina-De la Garza,
  • Elsa N. Garza-Treviño

DOI
https://doi.org/10.3390/biomedicines11020595
Journal volume & issue
Vol. 11, no. 2
p. 595

Abstract

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Background: Cancer treatment has many side effects; therefore, more efficient treatments are needed. Mesenchymal stem cells (MSC) have immunoregulatory properties, tumor site migration and can be genetically modified. Some proteins, such as soluble TRAIL (sTRAIL) and interleukin-12 (IL-12), have shown antitumoral potential, thus its combination in solid tumors could increase their activity. Materials and Methods: Lentiviral transduction of bone marrow MSC with green fluorescent protein (GFP) and transgenes (sTRAIL and IL-12) was confirmed by fluorescence microscopy and Western blot. Soluble TRAIL levels were quantified by ELISA. Lymphoma L5178Y cells express a reporter gene (GFP/mCherry), and TRAIL receptor (DR5). Results: An in vivo model showed that combined treatment with MSC expressing sTRAIL+IL-12 or IL-12 alone significantly reduced tumor volume and increased survival in BALB/c mice (p p < 0.05). It presented less tissue dysplasia confirmed by fluorescence and hematoxylin–eosin dye; nevertheless, treatment not inhibited hepatic metastasis. Conclusions: MSC expressing IL-12, is or combination with BM-MSC expressing sTRAIL represents an antitumor strategy for lymphoma tumors since they increase survival and reduce tumor development. However, the combination did not show significative additive effect. The localized application did not inhibit metastasis but reduced morphological alterations of tissue associated with liver metastasis.

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