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

Summary

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.

Keywords

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

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Exosomes from adipose tissue-derived stem/stromal cells: A key to future regenerative medicine
JÉRÔME LALOZE, ALEXIS DESMOULIÈRE
BIOCELL, Vol.46, No.12, pp. 2701-2704, 2022, DOI:10.32604/biocell.2022.022229
（This article belongs to the Special Issue: Mesenchymal Stem Cells, Secretome and Biomaterials: Regenerative Medicine Application)
Abstract Advances in regenerative medicine correlate strongly with progress in the use of adipose tissue-derived mesenchymal stem/stromal cells. The range of therapeutic indications has also expanded over recent years. Numerous recent studies have highlighted the primary importance of paracrine secretion by these cells. Though it is interesting to compare the different types of such secretions, we believe that exosomes (extra-cellular vesicles possessing the same properties as their source cells) will likely be the main key in tomorrow’s cell therapy. Exosomes also have many advantages compared to the direct use of cells, making these particles a major More >

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Mesenchymal stem cell-derived exosomes as new remedy for the treatment of inflammatory eye diseases
CARL RANDALL HARRELL, ANA VOLAREVIC, DRAGICA PAVLOVIC, VALENTIN DJONOV, VLADISLAV VOLAREVIC
BIOCELL, Vol.46, No.10, pp. 2195-2200, 2022, DOI:10.32604/biocell.2022.020175
（This article belongs to the Special Issue: Mesenchymal Stem Cells, Secretome and Biomaterials: Regenerative Medicine Application)
Abstract Detrimental immune response has a crucially important role in the development and progression of inflammatory eye diseases. Inflammatory mediators and proteolytic enzymes released by activated immune cells induce serious injury of corneal epithelial cells and retinal ganglion cell which may result in the vision loss. Mesenchymal stem cells (MSCs) are regulatory cells which produce various immunosuppressive factors that modulate phenotype and function of inflammatory immune cells. However, several safety issues, including undesired differentiation and emboli formation, limit clinical use of MSCs. MSC-derived exosomes (MSC-Exos) are nano-sized extracellular vesicles which contain all MSC-derived immunoregulatory factors. Intraocular More >

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Mesenchymal stem cells, the secretome and biomaterials: Regenerative medicine application
KI-TAEK LIM, TEJAL V. PATIL, DINESH K. PATEL, SAYAN DEB DUTTA, KEYA GANGULY, AAYUSHI RANDHAWA
BIOCELL, Vol.46, No.10, pp. 2201-2208, 2022, DOI:10.32604/biocell.2022.020013
（This article belongs to the Special Issue: Mesenchymal Stem Cells, Secretome and Biomaterials: Regenerative Medicine Application)
Abstract Mesenchymal stem cells (MSCs) are multipotent cells usually isolated from bone marrow, endometrium, adipose tissues, skin, and dental pulp. MSCs played a crucial role in regenerative therapy and have been introduced as an interdisciplinary field between cell biology and material science. Recently, MSCs have been widely explored for their application in regenerative medicine and COVID-19 treatment. Different approaches to evaluate the future of biomaterials and stem cell properties have been developed. However, misconceptions and ethical issues still exist, such as MSCs being non-angiogenic, anti-apoptotic, and immunoregulatory competencies. Embryonic stem cells isolation primarily requires the consent… More >

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Inflammatory priming of mesenchymal stem cells: Focus on growth factors enhancement
ALEKSANDRA GORNOSTAEVA, ELENA ANDREEVA, LUDMILA BURAVKOVA
BIOCELL, Vol.46, No.9, pp. 2049-2052, 2022, DOI:10.32604/biocell.2022.019993
（This article belongs to the Special Issue: Mesenchymal Stem Cells, Secretome and Biomaterials: Regenerative Medicine Application)
Abstract Multipotent mesenchymal stromal cells (MSCs) are actively involved in reparation and inflammation processes, providing damaged tissue reparation and suppressing immune cell responses in vivo. The effects are mostly due to the production of a wide range of paracrine factors, including growth factors and immunomodulatory mediators. To induce immunosuppressive activity, MSCs are primed by inflammatory cytokines, which results in an increased production of immunomodulatory molecules. However, stimulation of reparative properties is also necessary. This viewpoint manuscript highlights the possibilities of inflammatory priming to increase the production of growth factors by MSCs. More >

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Mesenchymal stem cell secretome and nanotechnology: Combining therapeutic strategies
ADRIANA L. FERREIRA, GUSTAVO C. PARIS, ALINE DE A. AZEVEDO, ERIKA A. C. CORTEZ, SIMONE N. CARVALHO, LAIS DE CARVALHO, ALESSANDRA A. THOLE
BIOCELL, Vol.46, No.8, pp. 1807-1813, 2022, DOI:10.32604/biocell.2022.019363
（This article belongs to the Special Issue: Mesenchymal Stem Cells, Secretome and Biomaterials: Regenerative Medicine Application)
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… More >

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Production of mesenchymal stem cell derived-secretome as cell-free regenerative therapy and immunomodulation: A biomanufacturing perspective
FUAD GANDHI TORIZAL, FRANSISCUS FIANO ANTHONY KERANS, ANNISA KHUMAIRA
BIOCELL, Vol.46, No.8, pp. 1885-1891, 2022, DOI:10.32604/biocell.2022.019591
（This article belongs to the Special Issue: Mesenchymal Stem Cells, Secretome and Biomaterials: Regenerative Medicine Application)
Abstract The potential of mesenchymal stem cells (MSCs) in regenerative medicine has been largely known due to their capability to induce tissue regeneration in vivo with minimum inflammation during implantation. This adult stem cell type exhibit unique features of tissue repair mechanism and immune modulation mediated by their secreted factors, called secretome. Recently, the utilization of secretome as a therapeutic agent provided new insight into cell-free therapy. Nevertheless, a sufficient amount of secretome is necessary to realize their applications for translational medicine which required a proper biomanufacturing process. Several factors related to their production need to More >

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Mesenchymal stem cells, secretome and biomaterials in in-vivo animal models: Regenerative medicine application in cutaneous wound healing
MASSIMO CONESE, AURELIO PORTINCASA
BIOCELL, Vol.46, No.8, pp. 1815-1826, 2022, DOI:10.32604/biocell.2022.019448
（This article belongs to the Special Issue: Mesenchymal Stem Cells, Secretome and Biomaterials: Regenerative Medicine Application)
Abstract The treatment of nonhealing and chronic cutaneous wounds still needs a clinical advancement to be effective. Both mesenchymal stem cells (MSCs), obtained from different sources, and their secretome derived thereof (especially exosomes) can activate signaling pathways related to promotion of cell migration, vascularization, collagen deposition, and inflammatory response demonstrating prohealing, angiogenetic and anti-scarring capacities. On the other hand, biodegradable biomimetic scaffolds can facilitate endogenous cell attachment and proliferation as well as extracellular matrix production. In this Review, we revise the complex composites made by biomimetic scaffolds, mainly hydrogels, and MSC-derived exosomes constructed for cutaneous wound More >

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Characterization of three-dimensional multipotent adipose-derived stem cell spheroids
HONGYANG LI, CHAN WANG, SHIWEI LIU, YONGLONG GUO, JIANSU CHEN
BIOCELL, Vol.46, No.7, pp. 1705-1716, 2022, DOI:10.32604/biocell.2022.018442
（This article belongs to the Special Issue: Mesenchymal Stem Cells, Secretome and Biomaterials: Regenerative Medicine Application)
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… More >

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Precise tissue bioengineering and niches of mesenchymal stem cells: Their size and hierarchy matter
IGOR A. KHLUSOV, LARISA S. LITVINOVA, KRISTINA A. YUROVA, MARINA Y. KHLUSOVA
BIOCELL, Vol.46, No.6, pp. 1365-1373, 2022, DOI:10.32604/biocell.2022.018917
（This article belongs to the Special Issue: Mesenchymal Stem Cells, Secretome and Biomaterials: Regenerative Medicine Application)
Abstract Stem cell microterritories (niches), as a specialized part of the extracellular matrix (ECM), are considered an important target and tool for the development of new materials, medical implants, and devices. However, tissue bioengineering products that have stem cell niches of known size on the surface or in the bulk structure of artificial materials are practically unknown. This brief review attempts to draw attention to the problematic aspects of niches as specific parts of the ECM, such as their hierarchy and size for mesenchymal stromal/stem cells (MSCs). These parameters arise directly from numerous definitions of stem More >

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Tuning mesenchymal stem cell secretome therapeutic potential through mechanotransduction
GIORDANO WOSGRAU CALLONI, MARCO AUGUSTO STIMAMIGLIO
BIOCELL, Vol.46, No.6, pp. 1375-1381, 2022, DOI:10.32604/biocell.2022.019681
（This article belongs to the Special Issue: Mesenchymal Stem Cells, Secretome and Biomaterials: Regenerative Medicine Application)
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 More >

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Applications of scaffolds: Tools for enhancing the immunomodulation of mesenchymal stromal cells
OK-HYEON KIM, EUN RAN KIM, JUN HYUNG PARK, HYUN JUNG LEE
BIOCELL, Vol.46, No.6, pp. 1439-1443, 2022, DOI:10.32604/biocell.2022.018921
（This article belongs to the Special Issue: Mesenchymal Stem Cells, Secretome and Biomaterials: Regenerative Medicine Application)
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 More >

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New paradigms in regenerative engineering: Emerging role of extracellular vesicles paired with instructive biomaterials
W. BENTON SWANSON, YUJI MISHINA
BIOCELL, Vol.46, No.6, pp. 1445-1451, 2022, DOI:10.32604/biocell.2022.018781
（This article belongs to the Special Issue: Mesenchymal Stem Cells, Secretome and Biomaterials: Regenerative Medicine Application)
Abstract Mesenchymal stem cells (MSCs) have long been regarded as critical components of regenerative medicine strategies, given their multipotency and persistence in a variety of tissues. Recently, the specific role of MSCs in mediating regenerative outcomes has been attributed (in part) to secreted factors from transplanted cells, namely extracellular vesicles. This viewpoint manuscript highlights the promise of cell-derived extracellular vesicles as agents of regeneration, enhanced by synergy with appropriate biomaterials platforms. Extracellular vesicles are a potentially interesting regenerative tool to enhance the synergy between MSCs and biomaterials. As a result, we believe these technologies will improve More >

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Mesenchymal stem cell-derived exosome: The likely game-changer in stem cell research
DICKSON KOFI WIREDU OCANSEY, XINWEI XU, LU ZHANG, FEI MAO
BIOCELL, Vol.46, No.5, pp. 1169-1172, 2022, DOI:10.32604/biocell.2022.018470
（This article belongs to the Special Issue: Mesenchymal Stem Cells, Secretome and Biomaterials: Regenerative Medicine Application)
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… More >

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Therapeutic mechanisms and routes of delivery of mesenchymal stem cells in veterinary medicine: A point of view
AMANDA BARACHO TRINDADE HILL, JONATHAN EDWIN BARACHO TRINDADE HILL
BIOCELL, Vol.46, No.5, pp. 1173-1176, 2022, DOI:10.32604/biocell.2022.018637
（This article belongs to the Special Issue: Mesenchymal Stem Cells, Secretome and Biomaterials: Regenerative Medicine Application)
Abstract Mesenchymal stem cells (MSCs) represent an important tool in veterinary regenerative medicine due to their ability to home to injury sites and secrete molecules that regulate niches into regenerative microenvironments. Successful cell therapy depends on many factors, including choice of administration route and application of understanding of cell potency and their therapeutic mechanisms. In this point of view, the authors leverage the tumultuous history of the field to demonstrate the need for clinicians to continually update themselves as new discoveries are made in order to avoid misalignments in the future, especially regarding administration routes and More >

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Secretome-microRNA and anti-proliferative APRO family proteins as cancer prevention and stem cell research strategies
YUKA IKEDA, NOZOMI NAGASE, AI TSUJI, KURUMI TANIGUCHI, YASUKO KITAGISHI, SATORU MATSUDA
BIOCELL, Vol.46, No.5, pp. 1163-1167, 2022, DOI:10.32604/biocell.2022.018177
（This article belongs to the Special Issue: Mesenchymal Stem Cells, Secretome and Biomaterials: Regenerative Medicine Application)
Abstract Stemness of cancer cells contains limitless self-renewal proliferation. For the purpose of proliferation, secretome might exert its effects via the paracrine signaling. Specific microRNAs enclosed in the secretome of cancer stem cells could regulate the expression of anti-proliferative APRO family proteins. The biological functions of APRO family proteins seems to be quite intricate, however, which might be a key modulator of microRNAs, then could regulate the proliferation of cancer cells. In addition to affecting proliferation/differentiation during cellular development, APRO family proteins might also play an imperious role on keeping homeostasis in healthy stem cells under a More >

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Stem cells in intervertebral disc regeneration–more talk than action?
PETRA KRAUS, ANKITA SAMANTA, SINA LUFKIN, THOMAS LUFKIN
BIOCELL, Vol.46, No.4, pp. 893-898, 2022, DOI:10.32604/biocell.2022.018432
（This article belongs to the Special Issue: Mesenchymal Stem Cells, Secretome and Biomaterials: Regenerative Medicine Application)
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 More >

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Mesenchymal stem cells-derived extracellular vesicles as ‘natural’ drug delivery system for tissue regeneration
KENJI TSUJI, SHINJI KITAMURA, JUN WADA
BIOCELL, Vol.46, No.4, pp. 899-902, 2022, DOI:10.32604/biocell.2022.018594
（This article belongs to the Special Issue: Mesenchymal Stem Cells, Secretome and Biomaterials: Regenerative Medicine Application)
Abstract Mesenchymal stem cells (MSCs) have abilities to mediate tissue protection through mechanisms of anti-apoptosis, anti-oxidative stress and anti-fibrosis as well as tissue regeneration through mechanisms of cell proliferation, differentiation and angiogenesis. These effects by MSCs are mediated by a variety of factors, including growth factors, cytokines and extracellular vesicles (EVs). Among these factors, EVs, containing proteins, mRNA and microRNAs (miRNA), may carry their contents into distant tissues with high stability. Therefore, the treatment with MSC-derived EVs may be promising as ‘natural’ drug delivery systems (DDS). Especially, the treatment of MSC-derived EVs with the manipulation of More >

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Controversies in therapeutic application of mesenchymal stem cell-derived secretome
FERENC SIPOS, GYÖRGYI MŰZES
BIOCELL, Vol.46, No.4, pp. 903-906, 2022, DOI:10.32604/biocell.2022.018200
（This article belongs to the Special Issue: Mesenchymal Stem Cells, Secretome and Biomaterials: Regenerative Medicine Application)
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. More >

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Evaluation of the hepatoprotective and antioxidant effects of Tegillarca granosa flesh body extract against potassium bromide toxicity via targeting the histomorphometry, chromosomal and expressions of TGF-β1, VEGF and COX-2 genes in rats
ALI H. ABU ALMAATY, BASMA M. HENDAM, FAYEZ ALTHOBAITI, EMAN FAYAD, YASMIN M. ABD EL-AZIZ
BIOCELL, Vol.46, No.1, pp. 219-234, 2022, DOI:10.32604/biocell.2022.017623
（This article belongs to the Special Issue: Mesenchymal Stem Cells, Secretome and Biomaterials: Regenerative Medicine Application)
Abstract The hepatotoxic effect of potassium bromide (KBr) on rat liver tissues were determined, as well as the potential protective effect of Tegillaraca granosa (T. granosa) flesh body extract. Twenty adult male albino rats were equally distributed into four groups; Group (I) treated with physiological saline (control group), Group (II) was orally gavaged by 200 mg/kg of T. granosa body extract day after day, Group (III) was intoxicated by KBr (150 mg/kg bwt day after day orally) and finally, Group (IV) was given a combination of T. granosa flesh body extract plus KBr with similar doses in the second and… More >

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Mesenchymal Stem Cells, Secretome and Biomaterials: Regenerative Medicine Application

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