Therapeutic potential of human mesenchymal stromal cells secreted components: a problem with standartization

Abstract

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.

A new clinical‐scale serum‐free xeno‐free medium efficient in ex vivo amplification of mesenchymal stromal cells does not support mesenchymal stem cells

“…Conversely, Xuri medium is able to support well, in the primary cultures, amplification of MStroC exhibiting post–progenitor cell characteristics. Depending on the main mechanism of therapeutic effect of MStroC, the cells obtained in Xuri medium might be either appropriate (immunomodulatory and secretory effect for example) or inadequate (direct regeneration of a tissue from MSCs), which remains to be further elucidated. This should be explored in more detail, since some serum‐free media were shown to impact the secretory and immunomodulatory capacities of MStroC and some others were shown to maintain the “stemness” and differentiation potential under serum‐free culture conditions, but only in the presence of native extracellular matrix …”

“Cell-Free Therapeutics” from Components Secreted by Mesenchymal Stromal Cells as a Novel Class of Biopharmaceuticals

“…We observed a substantial difference between several growth factor concentrations in MSC CM manufactured with two different media. Importantly, the variability of factor concentrations between two MSC CM reflected on their potency in vitro [26]. The presence or absence of a certain biologically active component in the culture medium can also affect the function of MSC.…”

“…As the most important type of cells involved in tissue repair and regeneration after injury are fibroblasts, one of the models for MSC CM potency measurement was the assessment of human skin fibroblasts migration in the model of the scratch assay. In this regard that angiogenesis is also an indispensable process for the successful regeneration of tissues, we additionally used a model of human endothelial cells direct migration upon MSC CM gradient [26].…”

Potency Assays for Mesenchymal Stromal Cell Secretome-Based Products for Tissue Regeneration

“…Nevertheless, the development of MSC secretome-based products still remains complicated [19][20][21]. Among many factors, one can select the development of potency assays as a substantial challenge.…”