Conditioned Medium from Human Mesenchymal Stromal Cells: Towards the Clinical Translation

Abstract

Mesenchymal stem/stromal cells (MSC) remain a promising tool for regenerative medicine as the efficacy of MSC-based cell therapy has been demonstrated for a broad spectrum of indications. Their therapeutic potency is mainly associated with their ability to secrete multiple factors critical for tissue regeneration. Due to comparable effects along with superior safety MSC conditioned medium (MSC-CM) containing a complex of MSC-secreted products is considered a reasonable alternative to cell therapy. However, the lack of standards regulating bioprocessing, use of proper auxiliary materials, and quality control complicates the development of MSC secretome-based therapeutics. In this study, we suggested several approaches addressing these issues. We manufactured 36 MSC-CM samples based on different xeno-free serum-free chemically defined media (DMEM-LG or MSC NutriStem® XF) using original protocols and considered total concentrations of regeneration-associated paracrine factors secreted by human adipose-derived MSC at each time-point of conditioning. Using regression analysis, we retrospectively predicted associations between concentrations of several components of MSC-CM and its biological activity to stimulate human dermal fibroblast and endothelial cell migration in vitro as routine examples of potency assays for cell-based products. We also demonstrated that the cell culture medium might affect MSC-CM biological activity to varying degrees depending on the potency assay type. Furthermore, we showed that regression analysis might help to overcome donor variability. The suggested approaches might be successfully applied for other cell types if their secretome was shown to be promising for application in regenerative medicine.

Combined Effects of Eicosapentaenoic Acid and Adipocyte Renin–Angiotensin System Inhibition on Breast Cancer Cell Inflammation and Migration

“…Adipose tissue is a major component of the breast tissue and is actively involved in forming TME; thus, adipose tissue through its inflammatory and lipogenic activities may increase the risk of BC development [3,40]. Human adipose CM is a source of various growth factors, several adipocyte secretory hormones, cytokines, and metabolites [41], which are immensely responsible for inducing expression of markers associated with breast cancer cell signaling, motility, and metastases [42,43]. Consistent with this, we have found increased inflammatory, IL-6, IL-8, NF-κB, and STAT3 mRNA expression as well as induced expression of the lipogenic enzyme FASN in both MCF-7 and MDA-MB-231 cells in response to human adipocyte CM.…”

Mircrining the injured heart with stem cell-derived exosomes: an emerging strategy of cell-free therapy

“…Since then, favorable data in this regard have kept pouring in to show that the secreted bioactive molecules are cytoprotective, anti-apoptotic, pro-proliferative, and effective in preconditioning of stem cells to support their cardiomyogenic differentiation [128][129][130]. Efforts are underway to develop a standard protocol for bioprocessing and quality control of the conditioned medium for optimal therapeutic usage [131]. The exosome-based strategy is fast-emerging as an alternative to the conditioned medium-based cell-free therapy approach [132].…”

Secretome of Adipose Tissue-Derived Stem Cells (ASCs) as a Novel Trend in Chronic Non-Healing Wounds: An Overview of Experimental In Vitro and In Vivo Studies and Methodological Variables

“…Besides, one of the real issues is the use, in most of the studies reported, of FBS for the expansion of ASCs. Indeed, it is well known that this approach is not suitable for clinical use of ASCs or their secretome, due to the risk of transmission of disease as well as xenogeneic immune reactions in the transplanted host [33,86]. In this regard, recently, human serum albumin (HSA), human serum (HS), or knockout serum replacement (KSR) have been suggested as useful replacements of FBS for ASC cryopreservation and clinical banking [87].…”