Regenerative medicine approaches, such as replacement of damaged tissue by ex vivo manufactured constructions or stimulation of endogenous reparative and regenerative processes to treat different diseases, are actively developing. One of the major tools for regenerative medicine are stem and progenitor cells, including multipotent mesenchymal stem/stromal cells (MSC). Because the paracrine action of bioactive factors secreted by MSC is considered as a main mechanism underlying MSC regenerative effects, application of MSC extracellular secreted products could be a promising approach to stimulate tissue regeneration; it also has some advantages compared to the injection of the cells themselves. However, because of the complexity of composition and multiplicity of mechanisms of action distinguished the medicinal products based on bioactive factors secreted by human MSC from the most of pharmaceuticals, it is important to develop the approaches to their standardization and quality control. In the current study, based on the literature data and guidelines as well as on our own experimental results, we provided rationalization for nomenclature and methods of quality control for the complex of extracellular products secreted by human adipose-derived MSC on key indicators, such as "Identification", "Specific activity" and "Biological safety". Developed approaches were tested on the samples of conditioned media contained products secreted by MSC isolated from subcutaneous adipose tissue of 30 donors. This strategy for the standardization of innovative medicinal products and biomaterials based on the bioactive extracellular factors secreted by human MSC could be applicable for a wide range of bioactive complex products, produced using the different types of stem and progenitor cells.
V nastoiashchee vremia aktivno razrabatyvaiutsia podkhody regenerativnoĭ meditsiny, napravlennye kak na sozdanie zameshchaiushchikh povrezhdennye tkani konstruktsiĭ ex vivo, tak i na stimuliatsiiu éndogennykh protsessov reparatsii i regeneratsii pri razlichnykh zabolevaniiakh. Odnim iz osnovnykh instrumentov regenerativnoĭ meditsiny iavliaiutsia stvolovye i progenitornye kletki, k kotorym otnosiatsia mul'tipotentnye mezenkhimnye stvolovye/stromal'nye kletki (MSK). Poskol'ku osnovnym mekhanizmom regeneratornykh éffektov MSK schitaetsia parakrinnoe deĭstvie biologicheski aktivnykh faktorov, sekretiruemykh étimi kletkami, primenenie ékstratselliuliarnykh produktov sekretsii MSK dlia stimuliatsii regeneratsii tkaneĭ iavliaetsia perspektivnym podkhodom i obladaet riadom preimushchestv po sravneniiu s vvedeniem samikh kletok. Odnako, uchityvaia slozhnost' kak sostava, tak i mekhanizma deĭstviia preparatov na osnove produktov sekretsii MSK, otlichaiushchie ikh ot bol'shinstva farmatsevticheskikh sredstv, aktual'noĭ problemoĭ iavliaetsia razrabotka podkhodov k ikh standartizatsii i kontroliu kachestva. V dannoĭ rabote na osnovanii analiza literatury, normativnoĭ dokumentatsii i sobstvennykh éksperimental'nykh dannykh byli obosnovany nomenklatura i metodiki kontrolia kachestva ékstratselliuliarnogo kompleksa produktov sekretsii MSK zhirovoĭ tkani cheloveka po kliuchevym pokazateliam “Podlinnost'”, “Spetsificheskaia aktivnost'” i “Biologicheskaia bezopasnost'”. Aprobatsiia razrabotannykh podkhodov byla provedena na obraztsakh konditsionirovannoĭ sredy, soderzhashcheĭ produkty sekretsii MSK, vydelennykh iz podkozhnoĭ zhirovoĭ tkani 30 donorov. Razrabotannaia i aprobirovannaia nami strategiia standartizatsii dlia innovatsionnykh lekarstvennykh sredstv i biomaterialov na osnove biologicheski aktivnogo kompleksa produktov sekretsii MSK cheloveka mozhet byt' primenena k shirokomu krugu bioaktivnykh produktov slozhnogo sostava, poluchennykh s ispol'zovaniem razlichnykh tipov stvolovykh i progenitornykh kletok.
Keywords: adipose-derived mesenchymal stem/stromal cells; quality control; regenerative medicine; standardization; stem/progenitor cell secreted products.