Special Issue "Mesenchymal Stem Cells, Secretome and Biomaterials: Regenerative Medicine Application"

Submission Deadline: 28 February 2022 (closed)
Guest Editors
Prof. Dr. Oriana Trubiani, Department of Innovative Technologies in Medicine & Dentistry, University “G. d’Annunzio”, Chieti-Pescara, 66100 Chieti, Italy; oriana.trubiani@unich.it

Dr. Francesca Diomede, Department of Innovative Technologies in Medicine & Dentistry, University “G. d’Annunzio”, Chieti-Pescara, 66100 Chieti, Italy; francesca.diomede@unich.it

Dr. Jacopo Pizzicannella, ASL02 Lanciano-Vasto-Chieti, “Ss. Annunziata” Hospital, 66100 Chieti, Italy; jacopo.pizzicannella@unich.it


Mesenchymal Stem Cells (MSCs) are adult stem cells which can be isolated from human source. Human MSCs (hMSCs) are the non-haematopoietic, multipotent stem cells with the capacity to differentiate into mesodermal, endodermal and ectodermal lineages. MSCs express cell surface markers like cluster of differentiation (CD) 29, CD44, CD73, CD90, CD105 and lack the expression of CD14, CD34, CD45 and HLA (human leucocyte antigen)-DR. For the first time, hMSCs, were described in the bone marrow and till now they have been isolated from various sources, as adipose tissue, amniotic fluid, endometrium, dental tissues, and umbilical cord. hMSCs are able to maintain their stemness properties and features for long-term in vitro passage. MSCs show immunomodulatory features, release cytokines and immune-receptors which regulate the microenvironment in the host tissue.


Manipulation of stem cells or stem cells-derived secretome has emerged as a novel alternative therapeutic option for several diseases or in regenerative medicine in order to improve scaffold effects. Stem cells secretome exert its therapeutic effects mainly through the paracrine signaling of exosomes/microvesicles secreted into cell culture conditioned medium. These are small membrane vesicles released by a variety of cell types, containing functional cytokines and other proteins, lipids and nucleic acids, such as mRNA and microRNA. The soluble bioactive molecules present in the conditioned medium directly activate the target cells, suppress pro-inflammatory responses, modulate the immune system, inhibit apoptosis and fibrosis, and stimulate tissue-intrinsic progenitor cells differentiation. The stem cells secretome could provide a novel cell-free regenerative therapeutical approach in various diseases and in regenerative medicine.  


Then, to evaluate the aptitude of secretome derived from stem cells in terms of tissue regeneration we invite authors to contribute with original research articles, reviews and opinion letters focused on the use of secretome-derived stem cells for future clinical applications.


Potential topics include but are not limited to the following:


•Mesenchymal stem cells models for drug personalized therapy;

•Functionalized biomaterial with mesenchymal stem cells;

•Functionalized biomaterial with secretome;

•Mesenchymal stem cells secretome;

•Mesenchymal stem cells models of systemic and genetic diseases.

Mesenchymal Stem Cells, Secretome, Extracellular Vesicles, Exosomes, Biomaterials, Regenerative Medicine, Tissue Engineering.

Published Papers

  • Mesenchymal stem cell secretome and nanotechnology: Combining therapeutic strategies
  • Abstract Mesenchymal stem cells (MSC) have pushed the field of stem cell-based therapies by inducing tissue regeneration, immunosuppression, and angiogenesis mainly through vesicles and soluble factors release (paracrine signaling). MSC-extracellular vesicles (MSC-EV) adaptable secretome and homing to injured sites allowed researchers to unlock a new era of cell-free based therapy. In parallel, nanoparticles (NP) have been explored in contributing to transport and drug delivery systems, giving drugs desired physical-chemical properties to exploit cell behavior. However, NPs can be quickly recognized by immune cells and cleared from circulation. In this viewpoint, we explore how combining both therapeutic strategies can improve efficacy and… More
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  • Characterization of three-dimensional multipotent adipose-derived stem cell spheroids
  • Abstract Human adipose stem cells (hADSCs) are reliable sources for cell therapy. However, the clinical applications are limited by the decrease in activity during in vitro culture. We used a knockout serum replacement (KSR) medium, Eppendorf (EP) tube culture, and a simulated microgravity (SMG) culture system to establish hADSC spheroids. We found that hADSCs aggregated and formed spheroids in the KSR culture medium. The EP tube culture method revealed many biological cell characteristics, such as good cell viabilities, rough surfaces, polar growth, fusion phenomenon, and injectability. The findings show its advantages for hADSCs spherical cultures. When cultured in SMG, hADSC spheroids… More
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  • Tuning mesenchymal stem cell secretome therapeutic potential through mechanotransduction
  • Abstract Mesenchymal stem cells (MSCs) and their byproducts have been widely validated as potential therapeutic products for regenerative medicine. The therapeutic effects result mainly from the paracrine activity of MSCs, which consists of the secretion of bioactive molecules, whether dispersed in medium conditioned by cell culture or encapsulated in extracellular vesicles. The composition of the MSC secretome, which represents the set of these secreted cellular products, is crucial for the performance of the desired therapeutic functions. Different cell culture strategies have been employed to adjust the secretome composition of MSCs to obtain the best therapeutic responses for different clinical contexts. However,… More
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  • Applications of scaffolds: Tools for enhancing the immunomodulation of mesenchymal stromal cells
  • Abstract Exogenously delivered mesenchymal stromal cells (MSCs) are therapeutically beneficial owing to their paracrine effect; they secrete various cytokines, nucleic acids, and proteins. Multiple bioengineering techniques can help MSC cultures to release secretomes by providing stem cell niche-like conditions (both structurally and functionally). Various scaffolds mimic the natural extracellular matrix (ECM) using both natural and synthetic polymers, providing favorable environments for MSC proliferation and differentiation. Depending on material properties, either topographically or elastically structured scaffolds can be fabricated. Three-dimensional scaffolds have tunable substrate rigidities and structures, aiding MSC cultivation. Decellularized ECM-derived hydrogels are similar to the natural ECM, thus improving the… More
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  • Mesenchymal stem cell-derived exosome: The likely game-changer in stem cell research
  • Abstract Stem cell research is a promising area of transplantation and regenerative medicine with tremendous potential for improving the clinical treatment and diagnostic options across a variety of conditions and enhancing understanding of human development. Over the past few decades, mesenchymal stem cell (MSCs) studies have exponentially increased with a promising outcome. However, regardless of the huge investment and the research attention given to stem cell research, FDA approval for clinical use is still lacking. Amid the challenges confronting stem cell research as a cell-based product, there appears to be evidence of superior effect and heightened potential success in its expressed… More
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  • Stem cells in intervertebral disc regeneration–more talk than action?
  • Abstract Pain and lifestyle changes are common consequences of intervertebral disc degeneration (IVDD) and affect a large part of the aging population. The stemness of cells is exploited in the field of regenerative medicine as key to treat degenerative diseases. Transplanted cells however often face delivery and survival challenges, especially in tissues with a naturally harsh microniche environment such as the intervertebral disc. Recent interest in the secretome of stem cells, especially cargo protected from microniche-related decay as frequently present in degenerating tissues, provides new means of rejuvenating ailing cells and tissues. Exosomes, a type of extracellular vesicles with purposeful cargo… More
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  • Controversies in therapeutic application of mesenchymal stem cell-derived secretome
  • Abstract Though mesenchymal stem cells (MSCs) are considered as an important pillar of regenerative medicine, their regenerative potential has been shown to be limited in several pathological conditions. The adverse properties of MSC-based cell therapy have drawn attention to the therapeutic use of MSC-derived secretome. However, MSC-originated exosomes and microvesicles can also possess a significant impact on disease development, including cancer. By interchanging secretome, MSCs can interact with tumor cells and promote mutual exchange/induction of cellular markers. In addition, enzymes secreted into and activated within exosomes can result in the acquisition of new tumor cell properties. Therefore, therapeutic applications of MSC-derived… More
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