Biopolym. Cell. 2023; 39(3):209-219.
http://dx.doi.org/10.7124/bc.000A9A
Molecular and Cell Biotechnologies
Effects of transplantation of preconditioned mesenchymal stem cells seeded on a biomimetic 3D scaffold
1, 2Pokholenko I. O., 1, 2Pikus P. O., 1, 2Kovalchuk M. V., 1, 2Toporova O. K., 1, 2Rymar S. Y., 1Kordium V. A.
  1. Institute of Molecular Biology and Genetics, NAS of Ukraine
    150, Akademika Zabolotnoho Str., Kyiv, Ukraine, 03143
  2. SI “National scientific center “Institute of cardiology, clinical and regenerative medicine named after academician M.D. Strazhesko of NAMS of Ukraine”
    5, Sviatoslava Khorobroho Str., Kyiv, Ukraine, 03151

Abstract

Aim. The study aims to determine the effects of transplantation of preconditioned human umbilical cord mesenchymal stem cells (hUC-MSC) seeded on a biomimetic 3D scaffold. Methods. Porous collagen 3D scaffolds were prepared by freeze-drying collagen type I solutions. hUC-MSC were isolated by the explant method. The hUC-MSC were preconditioned with H2O2 or LPS for 24 hours, and the cells were seeded onto 3D collagen scaffolds. The effects of MSC preconditioning were studied on the xenogenic transplantation model. The scaffolds isolated five days after implantation were analyzed histologically and by the PCR-based detection of human-specific sequences in genomic DNA extracted from animal tissues. Results. The developed porous collagen scaffolds were able to support the adhesion and growth of hUC-MSC in vitro. The in vivo pro-angiogenic activity was mostly pronounced in hUC-MSC preconditioned with hydrogen peroxide compared to both native and LPS preconditioned hUC-MSC. The data from PCR analysis demonstrated prolonged retention of human DNA in the samples isolated from animals implanted with hUC-MSC preconditioned by low doses of hydrogen peroxide. That might suggest the prolonged survival of the cells in scaffolds upon implantation. Conclusions. hUC-MSC preconditioning with low doses of hydrogen peroxide increases their therapeutic potential.
Keywords: MSC, preconditioning, biomimetic 3D scaffolds, angiogenesis
Full text: (PDF, in English)

References

[1] Jovic D, Yu Y, Wang D, Wang K, Li H, Xu F, Liu C, Liu J, Luo Y. A Brief Overview of Global Trends in MSC-Based Cell Therapy. Stem Cell Rev Rep. 2022; 18(5):1525-45.
[2] Margiana R, Markov A, Zekiy AO, Hamza MU, Al-Dabbagh KA, Al-Zubaidi SH, Hameed NM, Ahmad I, Sivaraman R, Kzar HH, Al-Gazally ME, Mustafa YF, Siahmansouri H. Clinical application of mesenchymal stem cell in regenerative medicine: a narrative review. Stem Cell Res Ther. 2022; 13(1):366.
[3] Levy O, Kuai R, Siren EMJ, Bhere D, Milton Y, Nissar N, De Biasio M, Heinelt M, Reeve B, Abdi R, Alturki M, Fallatah M, Almalik A, Alhasan AH, Shah K, Karp JM. Shattering barriers toward clinically meaningful MSC therapies. Sci Adv. 2020; 6(30):eaba6884.
[4] Hu C, Li L. Preconditioning influences mesenchymal stem cell properties in vitro and in vivo. J Cell Mol Med. 2018; 22(3):1428-42.
[5] Kovalchuk MV, Shuvalova NS, Pokholenko IO, Draguljan MV, Gulko TP, Deryabina OG, Kordium VA. Monitoring of transplanted human Mesenchymal Stem Cells from Wharton's Jelly in xenogeneic systems in vivo. Biopolym Cell. 2015; 31(3):193-9.
[6] Maslova OO, Shuvalova NS, Sukhorada OM, Zhukova SM, Deryabina OG, Makarenko MV, Govseiev DO, Kordium VA. Heterogeneity of Umbilical Cords as a Source for Mesenchymal Stem Cells. Dataset Papers in Biology. 2013; 13:1-4.
[7] Rymar S, Pikus P, Buchek P, Shuvalova N, Pokholenko Ia, Irodov D, Kordium V. Comparison of the therapeutic effects of hUC-MSC intravenous delivery and intraperitoneal administration of MSCs encapsulated in alginate capsules for the treatment of rat liver cirrhosis. Biointerface Research in Applied Chemistry. 2022; 12(4):5054-70.
[8] Moshynets OV, Baranovskyi TP, Iungin OS, Krikunov AA, Potochilova VV, Rudnieva KL, Potters G, Pokholenko I. Therapeutic Potential of an Azithromycin-Colistin Combination against XDR K. pneumoniae in a 3D Collagen-Based In Vitro Wound Model of a Biofilm Infection. Antibiotics (Basel). 2023; 12(2):293.
[9] Pedretti SLDC, Rena CL, Orellano LAA, Lazari MG, Campos PP, Nunes TA. Benefits of pentoxifylline for skin flap tissue repair in rats. Acta Cir Bras. 2020; 35(11):e301105.
[10] Biase FH, Franco MM, Goulart LR, Antunes RC. Protocol for extraction of genomic DNA from swine solid tissues. Genet Mol Biol. 2002; 25(3):313-5.
[11] Becker M, Nitsche A, Neumann C, Aumann J, Junghahn I, Fichtner I. Sensitive PCR method for the detection and real-time quantification of human cells in xenotransplantation systems. Br J Cancer. 2002; 87(11):1328-35.
[12] Warburton PE, Greig GM, Haaf T, Willard HF. PCR amplification of chromosome-specific alpha satellite DNA: definition of centromeric STS markers and polymorphic analysis. Genomics. 1991; 11(2):324-33.
[13] Caplan H, Olson SD, Kumar A, George M, Prabhakara KS, Wenzel P, Bedi S, Toledano-Furman NE, Triolo F, Kamhieh-Milz J, Moll G, Cox CS Jr. Mesenchymal Stromal Cell Therapeutic Delivery: Translational Challenges to Clinical Application. Front Immunol. 2019; 10:1645.
[14] Bellis SL. Advantages of RGD peptides for directing cell association with biomaterials. Biomaterials. 2011; 32(18):4205-10.
[15] Kozaniti FK, Deligianni DD, Georgiou MD, Portan DV. The Role of Substrate Topography and Stiffness on MSC Cells Functions: Key Material Properties for Biomimetic Bone Tissue Engineering. Biomimetics (Basel). 2021; 7(1):7.
[16] Pikus PO, Rymar SY, Shuvalova NS, Kordium VA. Study of the interaction between macrophages and human umbilical cord MSCs in vivo on the model of perotonitis in mice. Biopolym Cell. 2022; 38(4):231-41.
[17] Nouri F, Nematollahi-Mahani SN, Sharifi AM. Preconditioning of Mesenchymal Stem Cells with Non-Toxic Concentration of Hydrogen Peroxide Against Oxidative Stress Induced Cell Death: The Role of Hypoxia-Inducible Factor-1. Adv Pharm Bull. 2019; 9(1):76-83.
[18] Kovalchuk MV, Shuvalova NS, Kordium VA. Donor variability of the Wharton jelly-derived MSCs in response to oxidative stress. Biopolym Cell. 2021; 37(6):419-27.
[19] Ti D, Hao H, Tong C, Liu J, Dong L, Zheng J, Zhao Y, Liu H, Fu X, Han W. LPS-preconditioned mesenchymal stromal cells modify macrophage polarization for resolution of chronic inflammation via exosome-shuttled let-7b. J Transl Med. 2015; 13:308.
[20] Nouri F, Nematollahi-Mahani SN, Sharifi AM. Preconditioning of Mesenchymal Stem Cells with Non-Toxic Concentration of Hydrogen Peroxide Against Oxidative Stress Induced Cell Death: The Role of Hypoxia-Inducible Factor-1. Adv Pharm Bull. 2019; 9(1):76-83.
[21] Wang D, Xie Y, Peng HQ, Wen ZM, Ying ZY, Geng C, Wu J, Lv HY, Xu B. LPS preconditioning of MSC-CM improves protection against hypoxia/reoxygenation-induced damage in H9c2 cells partly via HMGB1/Bach1 signalling. Clin Exp Pharmacol Physiol. 2022; 49(12):1319-33.
[22] Hashimoto T, Shibasaki F. Hypoxia-inducible factor as an angiogenic master switch. Front Pediatr. 2015; 3:33.