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.

Highlights

  • Stem cells are immature tissue precursor cells that are able to self-renew, have the ability to form clonal cell populations, and differentiate into multiple cell lineages [1,2]

  • Recent studies have brought attention to the wide array of bioactive factors produced by mesenchymal stem cell (MSC), which may play an important role in the regulation of numerous physiological processes [44]

  • We found that human uterine cervical stem cells (hUCESCs)-conditioned medium (CM) treatment significantly reduced mRNA expression of IL6, IL8, tumor necrosis factor α (TNFα) and MIP-1α pro-inflammatory cytokines, but increased mRNA expression of the IL10 anti-inflammatory cytokine, which is similar to results using MSC-CM from amniotic fluid in a mice colitis model [62]

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Summary

Stem Cells and Regenerative Medicine

Stem cells are immature tissue precursor cells that are able to self-renew, have the ability to form clonal cell populations, and differentiate into multiple cell lineages [1,2]. The Mesenchymal and Tissue Stem Cell Committee of the International Society for Cellular Therapy established in 2006 the minimal identifying characteristics for human MSCs [29]: (a) plastic-adherent cells when maintained in standard culture conditions; (b) expression of CD105, CD73 and CD90, and lack expression of CD45, CD34, CD14 or CD11b, CD79a or CD19 and HLA-DR surface molecules and (c) capacity to differentiate into osteoblasts, adipocytes and chondroblasts in vitro [29]. The secretome from MSCs has attracted much attention for its potential use in tissue repair and regeneration [43,45,46,47]

Secretome and Conditioned Media from MSCs as New Therapeutic Strategy
Immunomodulation and Antiinflammatory Activity
Anti-Apoptotic Activity
Wound Healing and Tissue Repair
Neuroprotective and Neurotrophic Effects
Angiogenesis Regulation
Antitumor Effect
Antimicrobial Effect
Differences in MSC-CM Composition and Need for Standardization
Exosomes from MSCs
Clinical Studies with Secretome from MSCs
Scalable Production of MSC Secretome
Inducing Secretory Modifications in MSCs
Hypoxia
Pro-Inflammatory Stimuli
Tri-Dimensional Growth
Microparticle Engineering
10. Conclusions
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