Mesenchymal Stem Cell Secretome: Toward Cell-Free Therapeutic Strategies in Regenerative Medicine

Abstract

Earlier research primarily attributed the effects of mesenchymal stem cell (MSC) therapies to their capacity for local engrafting and differentiating into multiple tissue types. However, recent studies have revealed that implanted cells do not survive for long, and that the benefits of MSC therapy could be due to the vast array of bioactive factors they produce, which play an important role in the regulation of key biologic processes. Secretome derivatives, such as conditioned media or exosomes, may present considerable advantages over cells for manufacturing, storage, handling, product shelf life and their potential as a ready-to-go biologic product. Nevertheless, regulatory requirements for manufacturing and quality control will be necessary to establish the safety and efficacy profile of these products. Among MSCs, human uterine cervical stem cells (hUCESCs) may be a good candidate for obtaining secretome-derived products. hUCESCs are obtained by Pap cervical smear, which is a less invasive and painful method than those used for obtaining other MSCs (for example, from bone marrow or adipose tissue). Moreover, due to easy isolation and a high proliferative rate, it is possible to obtain large amounts of hUCESCs or secretome-derived products for research and clinical use.

The extracellular vesicles‐derived from mesenchymal stromal cells: A new therapeutic option in regenerative medicine

“…These findings encouraged scientists to discover and empower the components of these paracrine factors in order to recapitulate the ability of these components to develop cell‐free transplant systems and hopefully to overcome the problems associated with cellular therapy. Further studies indicates that exosomes derived from cardiac progenitor cells mollify cardiomyocyte death in a murine model of ischemic‐reperfusion . Besides, cardiospher‐derived cells release exosomes that exert the same regenerative effect as their cells of origin in left ventricular dysfunction .…”

Mesenchymal Stromal Cells Anno 2019: Dawn of the Therapeutic Era? Concise Review

“…Other studies have demonstrated that the effects of MSCs can be mimicked by infusion of MSC conditioned culture medium . The MSC secretome may therefore be effective as a cell‐free therapy in regenerative medicine .…”

Ceramide and Exosomes: A Novel Target in Cancer Biology and Therapy

“…The importance of these factors does not vanish with the growing importance of exosomes. One has to realize that exosomes simply add to the secretome by stabilizing and combining certain signaling molecules such as miRNAs for long-distance communication and targeted delivery (for review on secretome, including EVs, see (Sinha et al, 2018; van der Pol, Boing, Harrison, Sturk, & Nieuwland, 2012; Vizoso, Eiro, Cid, Schneider, & Perez-Fernandez, 2017)). Enrichment of specific miRNAs in exosomes may be suitable for early diagnosis in cancer, but it still needs to be tested if the amount of miRNA transferred in exosomes is really sufficient to reprogram tissue for metastasis or fulfill other functions of exosomes found in vitro .…”