Conditioned Media from Mesenchymal Stem Cells as a Basis for Therapy

When culturing any type of cell, the culture media contents come to reflect the secreted molecules and extracellular vesicles of that cell type - what is called "conditioned media". It is a snapshot of the communications produced by the cell type in its current state. First generation stem cell therapies, in which the transplanted cells die rather than integrate with tissues in any useful number, influence health via the effects of their secretions and vesicles on native cells. It is much easier to build therapies based on the contents of the media rather than it is to transplant the cells themselves, from the perspective of storage, readiness, consistency of production, and so forth, and so this is the direction that the clinical industry has been taking for some years. Of course, nothing involving cells is ever simple, as this review notes.

Recently published studies suggest that the paracrine substances released by mesenchymal stem cells (MSCs) are the primary motive behind the therapeutic action reported in these cells. Pre-clinical and clinical research on MSCs has produced promising outcomes. Furthermore, these cells are generally safe for therapeutic use and may be extracted from a variety of anatomical regions. Recent research has indicated, however, that transplanted cells do not live long and that the advantages of MSC treatment may be attributable to the large diversity of bioactive substances they create, which play a crucial role in the control of essential physiological processes.

Secretome derivatives, such as conditioned media or exosomes, may provide significant benefits over cells in terms of manufacture, preservation, handling, longevity of the product, and potential as a ready-to-use biologic product. Despite their immunophenotypic similarities, the secretome of MSCs appears to vary greatly depending on the host's age and the niches in which the cells live. The secretome's effect on multiple biological processes such as angiogenesis, neurogenesis, tissue repair, immunomodulation, wound healing, anti-fibrotic, and anti-tumor for tissue maintenance and regeneration has been discovered. Defining the secretome of cultured cultivated MSC populations by conditioned media analysis will allow us to assess its potential as a novel treatment approach.

This review will concentrate on accumulating data from pre-clinical and clinical trials pointing to the therapeutic value of the conditioned medium. At last, the necessity of characterizing the conditioned medium for determining its potential for cell-free treatment therapy will be emphasized in this study.

Link: https://doi.org/10.33549/physiolres.935186

Comments

Long before the discovery of Shinya Yamanaka, back in 1981 it was possible to obtain iPSCs using the secretome or conditioned media from teratocarcinoma stem cells (https://www.ncbi.nlm.nih.gov/pmc/articles/PMC349323/).
What directly establishes a neoplastic state, namely cellular immortality and autonomy, still remains unknown (https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9330459)
Carrel and his associates Burrows and Ebeling had since the 1910's presented a series of publications claiming their successful in vitro immortalization of chick embryonic fibroblasts by continuing adding chick embryo extracts into the culture of chick embryonic heart tissue, although many contemporaries questioned this world's first success in transforming cells in vitro (https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5314007/)
Many spontaneously-established cell lines show deletion in the INK4a/ARF locus 266-268, besides CpG island methylation of the p16 gene within this locus
(https://www.ncbi.nlm.nih.gov/pmc/articles/PMC121409/)

Posted by: Dmitry Dzhagarov at November 8th, 2023 5:29 PM
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