Cytotherapy refers to the use of newly generated cells in the subject to produce therapeutic effects against diseases. The mesenchymal cells are well known to provide therapeutic effects with their paracrine secretions. However, there are several Challenges with the reliability and scalability of these cells on a large scale. To overcome this challenge, MSC-derived exosomes, which depict similar therapeutic effects against disease without the issue of scalability, are produced. These cells were found to decrease the production of tumor cells in mice. It was found that topically used exosomes penetrate deep into the psoriatic stratum corneum layer of the skin. This causes the inhibition of the C5B9 complement, which in turn inhibits attenuated neutrophil secretion. This mechanism was found to decrease the effects of psoriasis 1L- 17 by superficial use of exosomes.
Major Regulatory Challenges For Using MSC as EV Producer Cell
During the studies, the MSC EV preparations were found to show good efficacy in animal models. Moreover, in some later studies, the exosomes showed good results in preliminary clinical trials on kidney diseases and cochlear implants. However, from the perspective of regulations, safety is a priority over the efficacy of cytotherapy. Moreover, there are some big challenges with the reproducibility of mesenchymal stem cell exosomal manufacturing.
Considerations for Resolving Heterogeneity of Primary MSC as EV Producer Cells
It was seen that the exosomal vesicles [EV] exhibited different functions when derived from the bone marrow of different MSC donors. This functional heterogeneity in EV preparations poses consistency Challenges in quality for manufacturing on a large scale. However, to overcome this challenge, immortalization of MSC can be used. The therapeutic effects of immortalization Exosomal vesicles reported good results in various preclinical trials. The use of immortalization will reduce the dependency on restoring MSC from donors.
Study on Development of Identity and Potency of MSC EV Preparations
Several suggestions for identification and potency metrics were given by regulatory councils and authorities, such as detecting the concentration of MSC surface antigens and non-MSC surface antigens. Also, the number of particles per unit weight protein/membrane lipids can be checked.
Immunomodulating Activity of Exosomes Explained
The immortalization of exosomes helps to decrease inflammation by producing anti-inflammatory cells. Additionally, they have also been observed to decrease the complement activation as well.
Using MSC Exosomes for Treating Psoriasis
Psoriasis is a highly inflammatory skin disease that usually shows symptoms of localized areas of skin. The complement activation of neutrophils in psoriatic disease leads to increased NETosis and IL-17 production.
Efficacy of Exosomes in Mouse Model
To investigate the efficacy of exosome vesicle preparation in psoriasis disease mouse models were used. MSC exosomes were produced in mice to check if they reduce the concentration of IL-17 and C5b-9 formation in psoriasis. It was proposed that the site and mechanism of action of Exosomes were around the stratum corneum layer of skin.
Summary:
The mesenchymal stem cell-induced exosomes were tested on animal models to check the efficacy of psoriatic disease. It was suggested that the use of exosome vesicles topically reduces the secretion of IL-17 and C5b- 9 and thus reduces the effect of psoriasis.
