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200 1 _aMicrocapsule-Based Dose-Dependent Regulation of the Lifespan and Behavior of Adipose-Derived MSCs as a Cell-Mediated Delivery System: In Vitro Study
_fI. A. Khlusov, K. A. Yurova, V. V. Shupletsova [et al.]
203 _aText
_celectronic
320 _a[References: 73 tit.]
330 _aThe development of “biohybrid” drug delivery systems (DDS) based on mesenchymal stem/stromal cells (MSCs) is an important focus of current biotechnology research, particularly in the areas of oncotheranostics, regenerative medicine, and tissue bioengineering. However, the behavior of MSCs at sites of inflammation and tumor growth is relevant to potential tumor transformation, immunosuppression, the inhibition or stimulation of tumor growth, metastasis, and angiogenesis. Therefore, the concept was formulated to control the lifespan of MSCs for a specific time sufficient for drug delivery to the target tissue by varying the number of internalized microcontainers. The current study addressed the time-dependent in vitro assessment of the viability, migration, and division of human adipose-derived MSCs (hAMSCs) as a function of the dose of internalized polyelectrolyte microcapsules prepared using a layer-by-layer technique. Polystyrene sulfonate (PSS)—poly(allylamine hydrochloride) (PAH)-coated spherical micrometer-sized (diameter ~2–3 µm) vaterite (CaCO3) microcapsules (PAH-PSS)6 with the capping PSS layer were prepared after dissolution of the CaCO3 core template. The Cell-IQ phase contrast imaging results showed that hAMSCs internalized all (PAH-PSS)6 microcapsules saturating the intercellular medium (5–90 particles per cell). A strong (r > 0.7) linear dose-dependent and time-dependent (up to 8 days) regression was observed between the in vitro decrease in cell viability and the number of internalized microvesicles. The approximate time-to-complete-death of hAMSCs at different concentrations of microcapsules in culture was 428 h (1:5 ratio), 339 h (1:10), 252 h (1:20), 247 h (1:45), and 170 h (1:90 ratio).
330 _aBy varying the number of microcontainers loaded into the cells (from 1:10 to 1:90), a dose-dependent exponential decrease in both the movement rate and division rate of hAMSCs was observed. A real-time cell analysis (RTCA) of the effect of (PAH-PSS)6 microcapsules (from 1:5 to 1:20) on hAMSCs also showed a dose- and time-dependent decrease in cell longevity after a 50h study at ratios of 1:10 and 1:20. The incorporation of microcapsules (1:5, 1:20, and 1:45) resulted in a dose-dependent increase in 24-48 h secretion of GRO-a (CXCL1), MIF, and SDF-1a (CXCL12) chemokines in hAMSC culture. In turn, the normalization or inhibition of chemokine secretion occurred after 72 h, except for MIF levels below 5-20 microcapsules, which were internalized by MSCs. Thus, the proposed concept of controlling the lifespan of MSC-based DDS using a dose of internalized PAH-PSS microcapsules could be useful for biomedical applications. (PAH-PSS)6 microcapsule ratios of 1:5 and 1:10 have little effect on the lifespan of hAMSCs for a long time (up to 14-18 days), which can be recommended for regenerative therapy and tissue bioengineering associated with low oncological risk. The microcapsule ratios of 1:20 and 1:45 did not significantly restrict the migratory activity of hAMSCs-based DDS during the time interval required for tissue delivery (up to 4-5 days), followed by cell death after 10 days. Therefore, such doses of microcapsules can be used for hAMSC-based DDS in oncotheranostics.
461 _tInternational Journal of Molecular Sciences
463 _tVol. 24, iss. 1
_v[292, 20 p. ]
_d2023
610 1 _aтруды учёных ТПУ
610 1 _aэлектронный ресурс
610 1 _ahuman adipose-derived MSCs
610 1 _apolyelectrolyte microcapsules
610 1 _alayer-by-layer technique
610 1 _aphagocytosis
610 1 _acell viability
610 1 _amigration
610 1 _adivision
701 1 _aKhlusov
_bI. A.
_cbiophysicist
_cProfessor of Tomsk Polytechnic University, doctor of medical Sciences
_f1963-
_gIgor Albertovich
_2stltpush
_3(RuTPU)RU\TPU\pers\34907
701 1 _aYurova
_bK. A.
701 1 _aShupletsova
_bV. V.
_gValeria
701 1 _aKhaziakhmatova
_bO.
_gOlga
701 1 _aMalashchenko
_bV. V.
_gVladimir
701 1 _aKudryavtseva
_bV. L.
701 1 _aKhlusova
_bM. Yu.
_gMarina
701 1 _aSukhorukov
_bG.
_gGleb
701 1 _aLitvinova
_bL.
_gLarisa
712 0 2 _aНациональный исследовательский Томский политехнический университет
_bИсследовательская школа химических и биомедицинских технологий
_c(2017- )
_h8120
_2stltpush
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_b63413507
_c20230322
_gRCR
856 4 _uhttps://doi.org/10.3390/ijms24010292
942 _cCF