Human Mesenchymal Stem Cells as a Carrier for a Cell-Mediated Drug Delivery

L S Litvinova; V V Shupletsova; O G Khaziakhmatova; A G Daminova; V L Kudryavtseva; K A Yurova; V V Malashchenko; N M Todosenko; V Popova; R I Litvinov; E I Korotkova; G B Sukhorukov; A J Gow; D Weissman; E N Atochina-Vasserman; I A Khlusov

doi:10.3389/fbioe.2022.796111

Human Mesenchymal Stem Cells as a Carrier for a Cell-Mediated Drug Delivery

Front Bioeng Biotechnol. 2022 Feb 24:10:796111. doi: 10.3389/fbioe.2022.796111. eCollection 2022.

Authors

L S Litvinova¹, V V Shupletsova¹, O G Khaziakhmatova¹, A G Daminova^{2

3

4}, V L Kudryavtseva⁵, K A Yurova¹, V V Malashchenko¹, N M Todosenko¹, V Popova⁶, R I Litvinov^{2

7}, E I Korotkova⁶, G B Sukhorukov^{5

8}, A J Gow⁹, D Weissman⁷, E N Atochina-Vasserman⁷, I A Khlusov^{1

10

11}

Affiliations

¹ Center for Immunology and Cellular Biotechnology, Immanuel Kant Baltic Federal University, Kaliningrad, Russia.
² Institute of Fundamental Medicine and Biology, Kazan Federal University, Kazan, Russia.
³ Kazan Institute of Biochemistry and Biophysics, FRC KSC of RAS, Kazan, Russia.
⁴ Interdisciplinary Center for Analytical Microscopy, Kazan Federal University, Kazan, Russia.
⁵ School of Engineering and Materials Science, Queen Mary University of London, London, United Kingdom.
⁶ School of Earth Sciences and Engineering, National Research Tomsk Polytechnic University, Tomsk, Russia.
⁷ Department of Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, United States.
⁸ Skolkovo Institute of Science and Technology, Moscow, Russia.
⁹ Department of Pharmacology and Toxicology, Ernest Mario School of Pharmacy, Rutgers, The State University of New Jersey, Piscataway, NJ, United States.
¹⁰ Department of Morphology and General Pathology, Siberian State Medical University, Tomsk, Russia.
¹¹ Research School of Chemistry and Applied Biomedical Sciences, National Research Tomsk Polytechnic University, Tomsk, Russia.

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.

Keywords: cell migration; cell-mediated drug delivery; human adipose-derived mesenchymal stromal/stem cells; synthetic microcapsules; target drug delivery.

Copyright © 2022 Litvinova, Shupletsova, Khaziakhmatova, Daminova, Kudryavtseva, Yurova, Malashchenko, Todosenko, Popova, Litvinov, Korotkova, Sukhorukov, Gow, Weissman, Atochina-Vasserman and Khlusov.