Abstract

A number of preclinical and clinical studies have demonstrated the efficiency of mesenchymal stromal cells to serve as an excellent base for a cell-mediated drug delivery system. Cell-based targeted drug delivery has received much attention as a system to facilitate the uptake a nd transfer of active substances to specific organs and tissues with high efficiency. Human mesenchymal stem cells (MSCs) are attracting increased interest as a promising tool for cell-based therapy due to their high proliferative capacity, multi-potency, and anti-inflammatory and immunomodulatory properties. In particular, these cells are potentially suitable for use as encapsulated drug transporters to sites of inflammation. Here, we studied the in vitro effects of incorporating synthetic polymer microcapsules at various microcapsule-to-cell ratios on the morphology, ultrastructure, cytokine profile, and migration ability of human adipose-derived MSCs at various time points post-phagocytosis. The data show that under appropriate conditions, human MSCs can be efficiently loaded with synthesized microcapsules without damaging the cell’s structural integrity with unexpressed cytokine secretion, retained motility, and ability to migrate through 8 μm pores. Thus, the strategy of using human MSCs as a delivery vehicle for transferring microcapsules, containing bioactive material, across the tissue–blood or tumor–blood barriers to facilitate the treatment of stroke, cancer, or inflammatory diseases may open a new therapeutic perspective.

Highlights

  • Messenger RNA- and DNA-based therapies are a rapidly developing direction in the biomedical field

  • Bovine serum albumin (BSA, MW), fluorescein isothiocyanate isomer I (FITC), phosphate-buffered saline (PBS), calcium chloride, sodium carbonate, poly (PAH), poly (PSS), minimum Essential Medium Eagle Alpha Modification (α-MEM), ITS Liquid Media Supplement, fetal bovine serum (FBS), L-glutamine, and penicillin/streptomycin were purchased from Sigma–Aldrich

  • These cells retained the typical hMSC markers during long-term culturing on plastic in the standard medium

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Summary

Introduction

Messenger RNA (mRNA)- and DNA-based therapies are a rapidly developing direction in the biomedical field. Efficient delivery of genetic material and other bioactive molecules, such as proteins and small molecules, to specific target sites remains a challenge. LNPs are widely used for the delivery of nucleic acids because of their efficacy in delivery along with their simple synthesis, small size, and serum stability (Mitchell et al, 2021). Ionizable LNP and ionizable amphiphilic Janus dendrimer (IAJD) delivery systems for mRNA are an ideal platform for the delivery of these nucleic acid therapies (Zhang et al, 2021). There is an urgent need for a delivery system that is similar to LNP in terms of biocompatibility, cell uptake, and release, but is capable of transferring genetic material with its long-term protection to the vast majority of specific target sites

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