Biopolym. Cell. 2017; 33(6):463-472.
http://dx.doi.org/10.7124/bc.000969
Discussions
Triggering effect of “therapeutic MSC”
1Kordium V. A., 1Irodov D. M., 2Chaikovsky Yu. B.
  1. Institute of Molecular Biology and Genetics, NAS of Ukraine
    150, Akademika Zabolotnoho Str., Kyiv, Ukraine, 03680
  2. Bogomolets National Medical University
    13, Shevchenko Blvd., Kyiv, Ukraine, 01601

Abstract

The use of MSCs as a therapeutic agent is proven to be highly successful in many cases. However, the effects obtained are often temporary, and not leading to complete recovery. The reasons of such phenomenon are discussed in the article and the concept of “triggering effects” of MSCs is substantiated. The effect consists of the fact, that signal molecules, secreted by MSCs after administration, on one hand reduce the cell damage severity, supports and heals the cells. And on the other hand, MSCs induce mobilization and activation of the own (resident) stem cells, which replace the damaged cells. The realization of the therapeutic effect depends on the presence or absence of genetically determined disorders.
Keywords: mesenchymal stem cells, triggering effect, mobilization, activation
Full text: (PDF, in English)

References

[1] Maehle AH. Ambiguous cells: the emergence of the stem cell concept in the nineteenth and twentieth centuries. Notes Rec R Soc Lond. 2011;65(4):359-78.
[2] Kalaszczynska I, Ferdyn K. Wharton's jelly derived mesenchymal stem cells: future of regenerative medicine? Recent findings and clinical significance. Biomed Res Int. 2015;2015:430847.
[3] Squillaro T, Peluso G, Galderisi U. Clinical Trials With Mesenchymal Stem Cells: An Update. Cell Transplant. 2016;25(5):829-48.
[4] Chen Y-S, Chen Y-A, Tsai P-H, Chen C-P, Shaw S-W, Hsuan Y. Mesenchymal stem cell: considerations for manufacturing and clinical trials on cell therapy product. Int J Stem Cell Res Ther. 2016; 3(1):029.
[5] Brunt KR, Weisel RD, Li RK. Stem cells and regenerative medicine - future perspectives. Can J Physiol Pharmacol. 2012;90(3):327-35.
[6] Crisan M, Yap S, Casteilla L, Chen CW, Corselli M, Park TS, Andriolo G, Sun B, Zheng B, Zhang L, Norotte C, Teng PN, Traas J, Schugar R, Deasy BM, Badylak S, Buhring HJ, Giacobino JP, Lazzari L, Huard J, Péault B. A perivascular origin for mesenchymal stem cells in multiple human organs. Cell Stem Cell. 2008;3(3):301-13.
[7] da Silva Meirelles L, Caplan AI, Nardi NB. In search of the in vivo identity of mesenchymal stem cells. Stem Cells. 2008;26(9):2287-99.
[8] de Girolamo L, Lucarelli E, Alessandri G, Avanzini MA, Bernardo ME, Biagi E, Brini AT, D'Amico G, Fagioli F, Ferrero I, Locatelli F, Maccario R, Marazzi M, Parolini O, Pessina A, Torre ML, Italian Mesenchymal Stem Cell Group. Mesenchymal stem/stromal cells: a new ''cells as drugs'' paradigm. Efficacy and critical aspects in cell therapy. Curr Pharm Des. 2013;19(13):2459-73.
[9] Bianco P, Robey PG, Simmons PJ. Mesenchymal stem cells: revisiting history, concepts, and assays. Cell Stem Cell. 2008;2(4):313-9.
[10] Iyer SS, Rojas M. Anti-inflammatory effects of mesenchymal stem cells: novel concept for future therapies. Expert Opin Biol Ther. 2008;8(5):569-81.
[11] Meirelles Lda S, Fontes AM, Covas DT, Caplan AI. Mechanisms involved in the therapeutic properties of mesenchymal stem cells. Cytokine Growth Factor Rev. 2009;20(5-6):419-27.
[12] Rahimzadeh A, Mirakabad FS, Movassaghpour A, Shamsasenjan K, Kariminekoo S, Talebi M, Shekari A, Zeighamian V, Ghalhar MG, Akbarzadeh A. Biotechnological and biomedical applications of mesenchymal stem cells as a therapeutic system. Artif Cells Nanomed Biotechnol. 2016;44(2):559-70.
[13] Klimczak A, Kozlowska U. Mesenchymal stromal cells and tissue-specific progenitor cells: their role in tissue homeostasis. Stem Cells Int. 2016;2016(2016):4285215.
[14] Poulsom R, Alison MR, Forbes SJ, Wright NA. Adult stem cell plasticity. J Pathol. 2002;197(4):441-56.
[15] Ikebe C, Suzuki K. Mesenchymal stem cells for regenerative therapy: optimization of cell preparation protocols. Biomed Res Int. 2014;2014:951512. PubMed Central
[16] Zhaoa Q, Ren H, Han Z. Mesenchymal stem cells: Immunomodulatory capability and clinical potential in immune diseases J Cell Immunother. 2016;2(1):3–20.
[17] Luk F, de Witte SF, Korevaar SS, Roemeling-van Rhijn M, Franquesa M, Strini T, van den Engel S, Gargesha M, Roy D, Dor FJ, Horwitz EM, de Bruin RW, Betjes MG, Baan CC, Hoogduijn MJ. Inactivated Mesenchymal Stem Cells Maintain Immunomodulatory Capacity. Stem Cells Dev. 2016;25(18):1342-54.
[18] Rymar SY et al. Human cord mesenchymal stem cells in correction of liver injury in CCl4 treated rats. Current Problems of Biology and Ecology. Materials of IP.(October, 3-7, 2016):455-457.
[19] Kordium VA, Irodov DM, Drahulian MV, Gulko TP, Buchek PV. Systemic disease as a model for development of the genetic ang cell tera y technologies. Visnik ukrains'kogo tovaristva genetikiv i selekcioneriv. 2016;14(1):16-26.
[20] Deryabina OG, Shuvalova NS, Kovalchuk MV, Minin YV, Deriabin OM, Kordium VA. Influence of xenogeneic mesenchymal stem cells transplantation on atrophic rhinitis in mice. Faktori eksperimental'noi evolucii organizmiv. 2015;16:42-5.
[21] Deryabina O, Shuvalova N, Maslova O, Minin Y, Karas G, Toporova O, Kordium V. UC-MSCs use for nasal mucosa atrophy restoration. Abstract book of World Conference on regenerative medicine, 21-23 October 2015, Leipzig, Germany published in Regenerative Medicine:213.
[22] Rudenko VA, Belskaia LN, Gnedkova IO, Pichkur OL, Verbovska SA, Poholenko YaO. Xenogenic transplantation of mesenchymal stem cells transfected by IL-10 gene as a method of cell therapy of experimental allergic encephalomyelitis. Zbirnyk naukovykh pratsʹ spivrobitnykiv NMAPO im. PL Shupyka. 2015;24(2):323-9.
[23] Kovalchuk MV, Deryabina OG, Pichkur LD, Verbovskaya SA, Shuvalova NS, Pichkur OL, Kordium VA. Distribution of transplanted human mesenchymal stem cells from Wharton’s Jelly in the central nervous systems of the EAE rats. Biopolym Cell. 2015; 31(5):371-8.
[24] Kovalchuk MV, Shuvalova NS, Pokholenko IO, Dragulyan 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.
[25] Pokholenko Ia, Shuvalova N, Gulko T, Ruban T, Ignatchenko P, Moshynets O, Kovalchuk M, Dubey I, Deryabina O, Kordium V. Characterization of the functionalized biodegradable collagen scaffold for 3D-culture of mesenchymal stem cells and their in vivo targeting. Abstracts book of Stem Cell Community Day. Hamburg, 4th April. 2017(1):13-14.
[26] Keating A. Mesenchymal stromal cells: new directions. Cell Stem Cell. 2012;10(6):709-16.
[27] Caplan AI. What's in a name? Tissue Eng Part A. 2010;16(8):2415-7.
[28] Alvarado AG, Lathia JD. Taking a Toll on Self-Renewal: TLR-Mediated Innate Immune Signaling in Stem Cells. Trends Neurosci. 2016;39(7):463-471.
[29] Hoogduijn MJ, Verstegen MM, Engela AU, Korevaar SS, Roemeling-van Rhijn M, Merino A, Franquesa M, de Jonge J, Ijzermans JN, Weimar W, Betjes MG, Baan CC, van der Laan LJ. No evidence for circulating mesenchymal stem cells in patients with organ injury. Stem Cells Dev. 2014;23(19):2328-35.
[30] Leibacher J, Henschler R. Biodistribution, migration and homing of systemically applied mesenchymal stem/stromal cells. Stem Cell Res Ther. 2016;7:7.
[31] Zhong J, Rajagopalan S. Dipeptidyl Peptidase-4 Regulation of SDF-1/CXCR4 Axis: Implications for Cardiovascular Disease. Front Immunol. 2015;6:477.
[32] Morikawa S, Mabuchi Y, Niibe K, Suzuki S, Nagoshi N, Sunabori T, Shimmura S, Nagai Y, Nakagawa T, Okano H, Matsuzaki Y. Development of mesenchymal stem cells partially originate from the neural crest. Biochem Biophys Res Commun. 2009;379(4):1114-9.
[33] Fiore EJ, Mazzolini G, Aquino JB. Mesenchymal Stem/Stromal Cells in Liver Fibrosis: Recent Findings, Old/New Caveats and Future Perspectives. Stem Cell Rev. 2015;11(4):586-97. PubMed PMID: 25820543.
[34] Eseonu OI, De Bari C. Homing of mesenchymal stem cells: mechanistic or stochastic? Implications for targeted delivery in arthritis. Rheumatology (Oxford). 2015;54(2):210-8.
[35] Rastaldi MP, Ferrario F, Giardino L, Dell'Antonio G, Grillo C, Grillo P, Strutz F, Müller GA, Colasanti G, D'Amico G. Epithelial-mesenchymal transition of tubular epithelial cells in human renal biopsies. Kidney Int. 2002;62(1):137-46.
[36] Kalluri R. EMT: when epithelial cells decide to become mesenchymal-like cells. J Clin Invest. 2009;119(6):1417-9.
[37] Acloque H, Adams MS, Fishwick K, Bronner-Fraser M, Nieto MA. Epithelial-mesenchymal transitions: the importance of changing cell state in development and disease. J Clin Invest. 2009;119(6):1438-49. PubMed Central
[38] Germani A, Foglio E, Capogrossi MC, Russo MA, Limana F. Generation of cardiac progenitor cells through epicardial to mesenchymal transition. J Mol Med (Berl). 2015;93(7):735-48.
[39] Corallino S, Malabarba MG, Zobel M, Di Fiore PP, Scita G. Epithelial-to-Mesenchymal Plasticity Harnesses Endocytic Circuitries. Front Oncol. 2015;5:45.
[40] Yoshida S, Kato T, Kato Y. EMT Involved in Migration of Stem/Progenitor Cells for Pituitary Development and Regeneration. J Clin Med. 2016;5(4). pii: E43.
[41] Pollard JW. Trophic macrophages in development and disease. Nat Rev Immunol. 2009;9(4):259-70.
[42] Hoeffel G, Wang Y, Greter M, See P, Teo P, Malleret B, Leboeuf M, Low D, Oller G, Almeida F, Choy SH, Grisotto M, Renia L, Conway SJ, Stanley ER, Chan JK, Ng LG, Samokhvalov IM, Merad M, Ginhoux F. Adult Langerhans cells derive predominantly from embryonic fetal liver monocytes with a minor contribution of yolk sac-derived macrophages. J Exp Med. 2012;209(6):1167-81.
[43] Schulz C, Gomez Perdiguero E, Chorro L, Szabo-Rogers H, Cagnard N, Kierdorf K, Prinz M, Wu B, Jacobsen SE, Pollard JW, Frampton J, Liu KJ, Geissmann F. A lineage of myeloid cells independent of Myb and hematopoietic stem cells. Science. 2012;336(6077):86-90.
[44] Gurtner GC, Chang E. "Priming" endothelial progenitor cells: a new strategy to improve cell based therapeutics. Arterioscler Thromb Vasc Biol. 2008;28(6):1034-5.
[45] Dimarino AM, Caplan AI, Bonfield TL. Mesenchymal stem cells in tissue repair. Front Immunol. 2013;4:201.
[46] Trimboli AJ, Fukino K, de Bruin A, Wei G, Shen L, Tanner SM, Creasap N, Rosol TJ, Robinson ML, Eng C, Ostrowski MC, Leone G. Direct evidence for epithelial-mesenchymal transitions in breast cancer. Cancer Res. 2008;68(3):937-45.
[47] Kucerova L, Matuskova M, Hlubinova K, Altanerova V, Altaner C. Tumor cell behaviour modulation by mesenchymal stromal cells. Mol Cancer. 2010;9:129.