DOCSLIB.ORG

Secretome of Mesenchymal Stem Cells and Its Potential Protective Effects on Brain Pathologies

Total Page：16

File Type：pdf, Size：1020Kb

Download full-text PDF Read full-text
Secretome of Mesenchymal Stem Cells and Its Potential Protective Effects on Brain Pathologies Molecular Neurobiology (2019) 56:6902–6927 https://doi.org/10.1007/s12035-019-1570-x Secretome of Mesenchymal Stem Cells and Its Potential Protective Effects on Brain Pathologies Eliana Baez-Jurado1 & Oscar Hidalgo-Lanussa1 & Biviana Barrera-Bailón1 & Amirhossein Sahebkar2,3,4 & Ghulam Md Ashraf5 & Valentina Echeverria6,7 & George E. Barreto1 Received: 25 October 2018 /Accepted: 18 March 2019 /Published online: 2 April 2019 # Springer Science+Business Media, LLC, part of Springer Nature 2019 Abstract Previous studies have indicated that mesenchymal stem cells (MSCs) have a fundamental role in the repair and regeneration of damaged tissues. There is strong evidence showing that much of the beneficial effects of these cells are due to the secretion of bioactive molecules—besides microRNAs, hormones, and neurotrophins—with anti-inflammatory, immunoregulatory, angio- genic, and trophic effects. These factors have been reported by many studies to possess protective effects on the nervous tissue. Although the beneficial effects of the secretory factors of MSCs have been suggested for various neurological diseases, their actions on astrocytic cells are not well understood. Hence, it is important to recognize the specific effects of MSCs derived from adipose tissue, in addition to the differences presented by the secretome, depending on the source and methods of analysis. In this paper, the different sources of MSCs and their main characteristics are described, as well as the most significant advances in regeneration and protection provided by the secretome of MSCs. Also, we discuss the possible neuroprotective mechanisms of action of the MSC-derived biomolecules, with special emphasis on the effect of MSCs derived from adipose tissue and their impact on glial cells and brain pathologies. Keywords Mesenchymal stem cells . Paracrine factors . Pathologies . Therapeutics . Secretome . Brain Abbreviations CNS Central nervous system ASCs Adult stem cells CM-A-MSC Conditioned medium of mesenchymal AFSCs Amniotic fluid stem cells cells derived from adipose tissue BM-MSC Conditioned medium of mesenchymal stem cells derived from bone marrow CM-MSCs Conditioned medium of mesenchymal stem cells * George E. Barreto [email protected]; [email protected] DPSCs Dental plug stem cells ESCs Embryonic stem cells 1 Departamento de Nutrición y Bioquímica, Facultad de Ciencias, EpSCs Epithelial stem cells Pontificia Universidad Javeriana, Bogotá, DC, Colombia FSC Fetal stem cells 2 Neurogenic Inflammation Research Center, Mashhad University of HSC Hematopoietic stem cells Medical Sciences, Mashhad, Iran HSC Hepatic stem cells 3 Biotechnology Research Center, Pharmaceutical Technology HI Hypoxic-ischemic Institute, Mashhad University of Medical Sciences, Mashhad, Iran IPSC Induced pluripotent stem cells 4 School of Pharmacy, Mashhad University of Medical Sciences, A-MSC Mesenchymal cells derived from Mashhad, Iran adipose tissue 5 King Fahd Medical Research Center, King Abdulaziz University, MSCs Mesenchymal stem cells Jeddah, Saudi Arabia BM-MSC Mesenchymal stem cells derived 6 Facultad de Ciencias de la Salud, Universidad San Sebastian, Lientur from bone marrow 1457, 4080871 Concepción, Chile hUCB-MSC Mesenchymal stem cells of the human 7 Research & Development Service, Bay Pines VAHealthcare System, umbilical cord Bay Pines, FL 33744, USA Mol Neurobiol (2019) 56:6902–6927 6903 L-MSC Mesenchymal stromal cells derived in tissue repair and wound closure [16, 17]. Furthermore, it from the limbus has been found that VEGF, FGF, CCL2 (MCP1), the hepato- NSC Neural stem cells cyte growth factor (HGF), and IGF-1 have protective func- PSC Pluripotent stem cells tions in different tissues. Specifically, the PDGF-BB, bFGF, ROS Oxygen species endothelial growth factor (EGF) [17, 18], brain-derived neu- RNS Reactive nitrogen species rotrophic factor (BDNF), nerve growth factor (NGF) [19–21], SCI Spinal cord injury IGF-1 [21], and glial-derived nerve growth factor (GDNF) TBI Traumatic brain injury [19] have been reported to exert protective effect specifically UCB Umbilical cord blood on the brain tissue [22, 23]. In this review, we present a general UCPVC Umbilical cord stem cells and integrated overview of current knowledge about MSCs, UCPVC Umbilical cord stem cells the mechanism of action of their bioactive molecules and/or WJSC Wharton gelatin stem cells factors, and the recent progress in the investigation of their potential regenerative and protective action on glial cells such as astrocytes, as well as on different pathologies of the Introduction CNS. Recent studies have demonstrated the ability of mesenchymal stem cells (MSCs) to differentiate into a variety of functional Diversity of MSC Sources: Greater tissues, which are often affected by different diseases and Opportunity in Cell Therapy injuries [1–3]. For this reason, MSCs have been considered as one of the most promising agents in regenerative therapy MSCs can be found in a variety of tissues in the body, and they for tissue replacement and repair. Efforts have been focused are the source of a natural response to traumatic onset and cell on studying and applying regenerative therapy with MSC for tissue regeneration. It is important to separate the embryonic some diseases and respiratory pathologies, hematopoietic dis- stem cells (ESCs) from fetal stem cells (FSCs) and adult stem eases, and diabetes [4, 5] as well as other pathologies that cells (ASCs), since they differ in the degree of cellular fate drastically affect the central nervous system (CNS), such as [24]. traumatic injury, stroke, and spinal cord injury, among others ESCs are pluripotent, while FSCs and ASCs are [6, 7]. multipotent. The pluripotent state implies that it can give rise This growing interest is based on the acquisition of knowl- to more than one type of differentiated cell line and edge to understand the signals that govern the therapeutic and multipotent cells have a restrictive potency due to the acquired regenerative function of stem cells, especially in tissues with- cell's ability to form a type of tissue depending on the germ out regenerative capacity [8]. The brain tissue is one of the layer from which they originated [25, 26]. ESCs come from tissues that have this characteristic because it cannot regener- lineages of blast cells and gastric (blastocyst, trophectoderm, ate its nerve cells; in this case, many studies have utilized and internal cell mass) [27–30]. On the other hand, it was MSCs to protect and improve neuronal function [9], but ig- initially thought that all the cell lineages of the ASCs came noring other cells with important functions such as astrocytes. from the mesoderm embryonic tissue [27], but later on, it was Additionally, the mechanism by which MSCs exert their effect observed that ASC cells differentiated into functional cells is still not clear. It is even believed that the protective and that originated from the ectoderm and the endoderm [31]. beneficial effects of MSCs are due to the presence of biomol- This suggests that ASCs originally formed from the three ecules and soluble factors that these cells produce and release embryonic germ layers (mesoderm, ectoderm, and endo- into their extracellular environment [10–12]. derm). ASCs have been found in almost all tissues, regardless Previous studies of the secretome of MSCs have revealed a the tissue has a great regenerative capacity or not, denoting the diversity of biomolecules with broad and essential functions important role as progenitors [8]. that may have important therapeutic implications in the clinic. In adult individuals, the stem cells are located in niches in These biomolecules are anti-apoptotic factors, growth factors the perivascular zone of all organs which are microenviron- such as vascular endothelial growth factor (VEGF), β fibro- ments that provide protection for different stimuli, like differ- blast growth factor (FGF), platelet-derived growth factor entiation and apoptosis, in addition to allowing them to main- (PDGF) and insulin-like growth factor (IGF-1), sphingosine- tain a balance between self-renewal and differentiation 1-phosphate (S1P) [13], anti-inflammatory factors such as tu- [32–35]. Even if all niches share the same expression of key mor necrosis factor β1 (TGF-β1), interleukin (IL-10) [14], molecules in different tissues, each niche has a molecular and antimicrobial chemokines (the chemokine (C-X-C motif) identity associated with the tissue to which it is related. They ligand (CXCL)10, CXCL8, CXCL1, CXCL6, chemokine (C- even share characteristics of pericytes in terms of phenotype, C motif) ligand (CCL)20, and CCL5) [15], all being involved marker expression, and differentiation capacity [32, 36]. This 6904 Mol Neurobiol (2019) 56:6902–6927 identity is mainly reflected in the presence of membrane re- have a greater commitment and their power varieties depend ceptors that are specific to each tissue for extracellular matrix on the location within the embryo. proteins and associated growth factors of the surrounding tis- Besides the controversy due to the ethics involved in work- sues [32, 33, 37]. The common molecules between niches can ing with human embryos [51, 52], the in vitro issue of low play diverse roles according to the embryonic origin and the embryo generation rate [53], and differentiation to obtain a specific functions of the specific tissues [33]. heterogeneous population [53], ESCs are currently being eval- According to Bieback et al. [38], MSCs comprise a diverse uated for several
Load more

Recommended publications
  • Proteomic Analysis of the Secretome and Exosomes of Feline Adipose-Derived Mesenchymal Stem Cells
    animals Article Proteomic Analysis of the Secretome and Exosomes of Feline Adipose-Derived Mesenchymal Stem Cells Antonio J. Villatoro 1,2,† , María del Carmen Martín-Astorga 1,† , Cristina Alcoholado 1 , María del Mar Sánchez-Martín 1 and José Becerra 1,3,4,* 1 Laboratory of Bioengineering and Tissue Regeneration, Department of Cell Biology, Genetics and Physiology, University of Málaga, IBIMA, 29071 Málaga, Spain; [email protected] (A.J.V.); [email protected] (M.d.C.M.-A.); [email protected] (C.A.); [email protected] (M.d.M.S.-M.) 2 Instituto de Immunología Clínica y Terapia Celular (IMMUNESTEM), 29071 Málaga, Spain 3 Biomedical Research Networking Center in Bioengineering, Biomaterials, and Nanomedicine (CIBER-BBN), 28029 Madrid, Spain 4 Andalusian Centre for Nanomedicine and Biotechnology, University of Málaga (BIONAND), 29590 Málaga, Spain * Correspondence: [email protected]; Tel.: +34-952-131966 † These authors contributed equally to the work. Simple Summary: The enormous advances in stem cell research have generated high expectations in the development of new therapies to repair or regenerate damaged tissues. For this reason, laboratory studies of stem cells enable scientists to learn about cells’ essential properties. Specifically, in recent years, therapies based on mesenchymal stem cells have become an interesting alternative for the treatment of different complex pathologies in veterinary medicine. Mesenchymal stem cells secrete a wide variety of therapeutic elements such as bioactive molecules and extracellular vesicles Citation: Villatoro, A.J.; (e.g., exosomes). Thus, it is essential to characterize them before future use as biotechnological Martín-Astorga, M.d.C.; Alcoholado, products. Therefore, the objective of this study was to determine and compare their protein profile C.; Sánchez-Martín, M.d.M.; Becerra, to understand better the mechanisms of action of these components and facilitate their possible J.
    [Show full text]
  • And Perinatal Human Amniotic Fluid Stem Cells
    International Journal of Molecular Sciences Article Comprehensive Profiling of Secretome Formulations from Fetal- and Perinatal Human Amniotic Fluid Stem Cells Ambra Costa 1, Davide Ceresa 2, Antonella De Palma 3 , Rossana Rossi 3 , Sara Turturo 1 , Sara Santamaria 4 , Carolina Balbi 5,6 , Federico Villa 7 , Daniele Reverberi 8, Katia Cortese 4 , Pierangela De Biasio 9, Dario Paladini 10 , Domenico Coviello 11, Silvia Ravera 4 , Paolo Malatesta 1,2, Pierluigi Mauri 3 , Rodolfo Quarto 1,2,* and Sveva Bollini 1,* 1 Experimental Biology Unit, Department of Experimental Medicine (DIMES), University of Genova, 16132 Genova, Italy; [email protected] (A.C.); [email protected] (S.T.); [email protected] (P.M.) 2 Cellular Oncology Unit, IRCCS Ospedale Policlinico San Martino, 16132 Genova, Italy; [email protected] 3 Proteomics and Metabolomics Unit, Institute for Biomedical Technologies (ITB-CNR), 20054 Milan, Italy; [email protected] (A.D.P.); [email protected] (R.R.); [email protected] (P.M.) 4 Human Anatomy Unit, Department of Experimental Medicine (DIMES), University of Genova, 16132 Genova, Italy; [email protected] (S.S.); [email protected] (K.C.); [email protected] (S.R.) 5 Laboratory of Cellular and Molecular Cardiology, Cardiocentro Ticino Foundation, 6900 Lugano, Switzerland; [email protected] 6 Center for Molecular Cardiology, University of Zurich, 8952 Zurich, Switzerland 7 Molecular Oncology and Angiogenesis Unit, IRCCS Ospedale Policlinico San Martino, 16132 Genova, Italy; Citation: Costa, A.; Ceresa, D.; De [email protected] 8 Molecular Pathology Unit, IRCCS Ospedale Policlinico, San Martino, 16132 Genova, Italy; Palma, A.; Rossi, R.; Turturo, S.; [email protected] Santamaria, S.; Balbi, C.; Villa, F.; 9 Prenatal Diagnosis and Perinatal Medicine Unit, IRCCS Ospedale Policlinico San Martino, Reverberi, D.; Cortese, K.; et al.
    [Show full text]
  • Case Series of the First Three Severe COVID-19 Patients Treated with The
    F1000Research 2021, 10:228 Last updated: 13 SEP 2021 CLINICAL PRACTICE ARTICLE Case series of the first three severe COVID-19 patients treated with the secretome of hypoxia-mesenchymal stem cells in Indonesia [version 2; peer review: 1 approved, 1 approved with reservations] Agung Putra 1-3, Agus Widyatmoko4, Sugeng Ibrahim1,5, Fajar Amansyah6, Farid Amansyah6, Mukti Arja Berlian7, Retnaningsih Retnaningsih 8, Zenitalia Pasongka9, Flora Eka Sari10, Basuki Rachmad11 1Stem Cell and Cancer Research (SCCR), Faculty of Medicine, Universitas Islam Sultan Agung (Unissula), Semarang, Central Java, Indonesia 2Department of Postgraduate Biomedical Science, Faculty of Medicine, Universitas Islam Sultan Agung (Unissula), Semarang, Central Java, Indonesia 3Department of Pathological Anatomy, Faculty of Medicine,, Universitas Islam Sultan Agung (Unissula), Semarang, Central Java, Indonesia 4Department of Internal Medicine, Faculty of Medicine, Universitas Muhammadiyah Yogyakarta, Yogyakarta, Yogyakarta, Indonesia 5Department of Molecular Biology, Faculty of Medicine, Universitas Katholik (Unika) Soegijapranata, Semarang, Central Java, Indonesia 6Department of Internal Medicine, Bhayangkara Hospital, Makassar, South Sulawesi, Indonesia 7Department of Internal Medicine, Dr. Esnawan Antariksa Air Force Hospital, Jakarta, Jakarta, Indonesia 8Department of Neurology and Intensive Care Unit, Kariadi Hospital, Universitas Diponegoro, Semarang, Central Java, Indonesia 9Faculty of Medicine, Universitas Udayana, Denpasar, Bali, Indonesia 10Department of Pulmonary
    [Show full text]
  • Molecular Mechanisms Responsible for Therapeutic Potential of Mesenchymal Stem Cell-Derived Secretome
    cells Review Molecular Mechanisms Responsible for Therapeutic Potential of Mesenchymal Stem Cell-Derived Secretome Carl Randall Harrell 1, Crissy Fellabaum 1 , Nemanja Jovicic 2 , Valentin Djonov 3, Nebojsa Arsenijevic 2 and Vladislav Volarevic 2,* 1 Regenerative Processing Plant, LLC, Palm Harbor, FL 34176, USA; [email protected] (C.R.H.); [email protected] (C.F.) 2 Department for Microbiology and Immunology, Center for Molecular Medicine and Stem Cell Research, Faculty of Medical Sciences, University of Kragujevac, 69 Svetozara Markovica Street, 34000 Kragujevac, Serbia; [email protected] (N.J.); [email protected] (N.A.) 3 Institute of Anatomy, University of Bern, Baltzerstrasse 2, 3012 Bern, Switzerland; [email protected] * Correspondence: [email protected]; Tel.: +38134306800 Received: 10 April 2019; Accepted: 30 April 2019; Published: 16 May 2019 Abstract: Mesenchymal stem cell (MSC)-sourced secretome, defined as the set of MSC-derived bioactive factors (soluble proteins, nucleic acids, lipids and extracellular vesicles), showed therapeutic effects similar to those observed after transplantation of MSCs. MSC-derived secretome may bypass many side effects of MSC-based therapy, including unwanted differentiation of engrafted MSCs. In contrast to MSCs which had to be expanded in culture to reach optimal cell number for transplantation, MSC-sourced secretome is immediately available for treatment of acute conditions, including fulminant hepatitis, cerebral ischemia and myocardial infarction. Additionally,MSC-derived secretome could be massively produced from commercially available cell lines avoiding invasive cell collection procedure. In this review article we emphasized molecular and cellular mechanisms that were responsible for beneficial effects of MSC-derived secretomes in the treatment of degenerative and inflammatory diseases of hepatobiliary, respiratory, musculoskeletal, gastrointestinal, cardiovascular and nervous system.
    [Show full text]
  • Engineering Mesenchymal Stem Cells to Improve Their
    JOURNAL OF EXTRACELLULAR VESICLES 2018, VOL. 7, 1522236 https://doi.org/10.1080/20013078.2018.1522236 REVIEW ARTICLE Engineering mesenchymal stem cells to improve their exosome efficacy and yield for cell-free therapy Jennifer Phan a,b, Priyadarsini Kumara,c, Dake Haoa,c, Kewa Gaoa,d, Diana Farmer a,c and Aijun Wang a,c aSurgical Bioengineering Laboratory, Department of Surgery, University of California, Davis School of Medicine, Sacramento, CA, USA; bCIRM Bridges to Stem Cell Research Program, California State University, Sacramento, CA, USA; cInstitute for Paediatric Regenerative Medicine, Shriners Hospital for Children/UC Davis School of Medicine, Sacramento, CA, USA; dDepartment of Burn and Plastic Surgery, The Third Xiangya Hospital of Central South University, Changsha, Hunan, P.R. China ABSTRACT ARTICLE HISTORY Through traditional medicine, there were diseases and disorders that previously remained Received 22 November 2017 untreated or were simply thought to be incurable. Since the discovery of mesenchymal stem Revised 8 August 2018 cells (MSCs), there has been a flurry of research to develop MSC-based therapy for diseases and Accepted 27 August 2018 disorders. It is now well-known that MSCs do not typically engraft after transplantation and KEYWORDS exhibit their therapeutic effect via a paracrine mechanism. In addition to secretory proteins, MSCs Mesenchymal stem cells; also produce extracellular vesicles (EVs), membrane-bound nanovesicles containing proteins, DNA extracellular vesicles and RNA. The secreted vesicles then interact with target cells and deliver their contents, impart- ing their ultimate therapeutic effect. Unlike the widely studied cancer cells, the yield of MSC- exosomes is a limiting factor for large-scale production for cell-free therapies.
    [Show full text]
  • The Extracellular Bone Marrow Microenvironment—A Proteomic Comparison of Constitutive Protein Release by in Vitro Cultured Osteoblasts and Mesenchymal Stem Cells
    cancers Article The Extracellular Bone Marrow Microenvironment—A Proteomic Comparison of Constitutive Protein Release by In Vitro Cultured Osteoblasts and Mesenchymal Stem Cells Elise Aasebø 1 , Even Birkeland 2, Frode Selheim 2, Frode Berven 2, Annette K. Brenner 1 and Øystein Bruserud 1,3,* 1 Department of Clinical Science, University of Bergen, N-5021 Bergen, Norway; [email protected] (E.A.); [email protected] (A.K.B.) 2 The Proteomics Facility of the University of Bergen (PROBE), University of Bergen, N-5021 Bergen, Norway; [email protected] (E.B.); [email protected] (F.S.); [email protected] (F.B.) 3 Department of Medicine, Haukeland University Hospital, N-5021 Bergen, Norway * Correspondence: [email protected] or [email protected]; Tel.: +47-5597-2997 Simple Summary: Normal blood cells are formed in the bone marrow by a process called hematopoiesis. This process is supported by a network of non-hematopoietic cells including connective tissue cells, blood vessel cells and bone-forming cells. However, these cells can also support the growth of cancer cells, i.e., hematological malignancies (e.g., leukemias) and cancers that arise in another organ and spread to the bone marrow. Two of these cancer-supporting normal cells are bone-forming osteoblasts and a subset of connective tissue cells called mesenchymal stem cells. One mechanism for their cancer support is the release of proteins that support cancer cell proliferation and progression of the cancer disease. Our present study shows that both these normal cells release a wide range of proteins that support cancer cells, and inhibition of this protein-mediated cancer support may become a new strategy for cancer treatment.
    [Show full text]
  • Mesenchymal Stromal/Stem Cell-Derived Extracellular Vesicles in Tissue Repair: Challenges and Opportunities
    Mesenchymal Stromal/Stem Cell-derived extracellular vesicles in tissue repair: challenges and opportunities Suzy Varderidou-Minasian1,2 and Magdalena J. Lorenowicz1,2 1Center for Molecular Medicine, University Medical Center Utrecht, Universiteitsweg 100, 3584 CG, Utrecht, The Netherlands 2Regenerative Medicine Center, Uppsalalaan 8, 3584 CT, Utrecht, The Netherlands Correspondence: Magdalena Lorenowicz, PhD Address: Regenerative Medicine Center, UMC Utrecht, Uppsalalaan 8, 3584CT Utrecht, The Netherlands Tel: +31- 88-755-67941 Email: [email protected] Abstract Mesenchymal stem/stromal cells (MSCs) are important players in tissue homeostasis and regeneration owing to their immunomodulatory potential and release of trophic factors that promote healing. They have been increasingly used in clinical trials to treat multiple conditions associated with inflammation and tissue damage such as graft versus host disease, orthopedic injuries and cardiac and liver diseases. Recent evidence demonstrates that their beneficial effects are derived, at least in part, from their secretome. In particular, data from animal models and first-in- man studies indicate that MSC-derived extracellular vesicles (MSC-EVs) can exert similar therapeutic potential as their cells of origin. MSC-EVs are membranous structures loaded with proteins, lipids, carbohydrates and nucleic acids, which play an important role in cell-cell communication and may represent an attractive alternative for cell-based therapy. In this article we summarize recent advances in the use of MSC-EVs for tissue repair. We highlight several isolation and characterization approaches used to enrich MSC-derived EVs. We discuss our current understanding of the relative contribution of the MSC-EVs to the immunomodulatory and regenerative effects mediated by MSCs and MSC secretome.
    [Show full text]
  • Secretome of Adipose-Derived Mesenchymal Stem Cells Promotes Skeletal Muscle Regeneration Through Synergistic Action of Extracel
    Mitchell et al. Stem Cell Research & Therapy (2019) 10:116 https://doi.org/10.1186/s13287-019-1213-1 RESEARCH Open Access Secretome of adipose-derived mesenchymal stem cells promotes skeletal muscle regeneration through synergistic action of extracellular vesicle cargo and soluble proteins Robert Mitchell1, Ben Mellows1, Jonathan Sheard2,3, Manuela Antonioli4, Oliver Kretz5,6, David Chambers8, Marie-Theres Zeuner2, James E. Tomkins2, Bernd Denecke9, Luca Musante10, Barbara Joch7, Florence Debacq-Chainiaux11, Harry Holthofer10,12, Steve Ray13, Tobias B. Huber5,6,12,14, Joern Dengjel12,15, Paolo De Coppi16, Darius Widera2* and Ketan Patel1,12* Abstract Background: The mechanisms underpinning the regenerative capabilities of mesenchymal stem cells (MSC) were originally thought to reside in their ability to recognise damaged tissue and to differentiate into specific cell types that would replace defective cells. However, recent work has shown that molecules produced by MSCs (secretome), particularly those packaged in extracellular vesicles (EVs), rather than the cells themselves are responsible for tissue repair. Methods: Here we have produced a secretome from adipose-derived mesenchymal stem cells (ADSC) that is free of exogenous molecules by incubation within a saline solution. Various in vitro models were used to evaluate the effects of the secretome on cellular processes that promote tissue regeneration. A cardiotoxin-induced skeletal muscle injury model was used to test the regenerative effects of the whole secretome or isolated extracellular vesicle fraction in vivo. This was followed by bioinformatic analysis of the components of the protein and miRNA content of the secretome and finally compared to a secretome generated from a secondary stem cell source.
    [Show full text]
  • Secretome and Extracellular Vesicles As New Biological Therapies for Knee Osteoarthritis: a Systematic Review
    Journal of Clinical Medicine Review Secretome and Extracellular Vesicles as New Biological Therapies for Knee Osteoarthritis: A Systematic Review Daniele D’Arrigo 1,2, Alice Roffi 3,*, Magali Cucchiarini 4 , Matteo Moretti 1,5, Christian Candrian 6 and Giuseppe Filardo 3,6 1 Regenerative Medicine Technologies Laboratory, Ente Ospedaliero Cantonale (EOC), Via Tesserete 46, 6900 Lugano, Switzerland; Daniele.D’[email protected] (D.D.A.); [email protected] (M.M.) 2 Department of Biotechnology and Biosciences, University of Milano-Bicocca, Piazza dell’ Ateneo Nuovo 1, 20126 Milano, Italy 3 Applied and Translational Research center (ATRc), IRCCS Istituto Ortopedico Rizzoli, Via di Barbiano 1/10, 40136 Bologna, Italy; ortho@gfilardo.com 4 Center of Experimental Orthopaedics, Saarland University Medical Center, 66421 Homburg, Germany; [email protected] 5 Cell and Tissue Engineering Laboratory, IRCCS Istituto Ortopedico Galeazzi, via Galeazzi, 4, 20161 Milan, Italy 6 Orthopaedic and Traumatology Unit, Ospedale Regionale di Lugano, Ente Ospedaliero Cantonale, Via Tesserete 46, 6900 Lugano, Switzerland; [email protected] * Correspondence: alice.roffi@ior.it; Tel.: +39-051-6366567 Received: 13 September 2019; Accepted: 23 October 2019; Published: 4 November 2019 Abstract: Secretome and extracellular vesicles (EVs) are considered a promising option to exploit mesenchymal stem cells’ (MSCs) properties to address knee osteoarthritis (OA). The aim of this systematic review was to analyze both the in vitro and in vivo literature, in order to understand the potential of secretome and EVs as a minimally invasive injective biological approach. A systematic review of the literature was performed on PubMed, Embase, and Web of Science databases up to 31 August 2019.
    [Show full text]
  • Therapeutic Use of Mesenchymal Stem Cell-Derived Exosomes: from Basic Science to Clinics
    pharmaceutics Review Therapeutic Use of Mesenchymal Stem Cell-Derived Exosomes: From Basic Science to Clinics Carl Randall Harrell 1, Nemanja Jovicic 2 , Valentin Djonov 3 and Vladislav Volarevic 4,5,* 1 Regenerative Processing Plant, LLC, 34176 US Highway 19 N Palm Harbor, Palm Harbor, FL 34684, USA; [email protected] 2 Department of Histology and Embryology, Faculty of Medical Sciences, University of Kragujevac, Svetozara Markovica 69, 34000 Kragujevac, Serbia; [email protected] 3 Institute of Anatomy, University of Bern, 2 Baltzerstrasse, 3012 Bern, Switzerland; [email protected] 4 Department for Microbiology and Immunology, Center for Molecular Medicine and Stem Cell Research, Faculty of Medical Sciences, University of Kragujevac, 69 Svetozar Markovic Street, 34000 Kragujevac, Serbia 5 Center of Excellence for the Acceleration of Harm Reduction (CoEHAR), Università di Catania, Via Santa Sofia 78, 95123 Catania, Italy * Correspondence: [email protected]; Tel.: +381-34306800; Fax: +381-34306800 Received: 31 March 2020; Accepted: 11 May 2020; Published: 22 May 2020 Abstract: Mesenchymal stem cells (MSC) are, due to their immunosuppressive and regenerative properties, used as new therapeutic agents in cell-based therapy of inflammatory and degenerative diseases. A large number of experimental and clinical studies revealed that most of MSC-mediated beneficial effects were attributed to the effects of MSC-sourced exosomes (MSC-Exos). MSC-Exos are nano-sized extracellular vesicles that contain MSC-derived bioactive molecules (messenger RNA (mRNA), microRNAs (miRNAs)), enzymes, cytokines, chemokines, and growth factors) that modulate phenotype, function and homing of immune cells, and regulate survival and proliferation of parenchymal cells. In this review article, we emphasized current knowledge about molecular and cellular mechanisms that were responsible for MSC-Exos-based beneficial effects in experimental models and clinical trials.
    [Show full text]
  • Stem Cell Secretome, Regeneration, and Clinical Translation: a Narrative Review
    70 Review Article Page 1 of 11 Stem cell secretome, regeneration, and clinical translation: a narrative review Chukwuweike Gwam, Nequesha Mohammed, Xue Ma Department of Orthopedic Surgery, Wake Forest School of Medicine, Wake Forest Baptist Medical Center, Winston-Salem, NC, USA Contributions: (I) Conception and design: All authors; (II) Administrative support: C Gwam, X Ma; (III) Provision of study materials or patients: All authors; (IV) Collection and assembly of data: C Gwam, N Mohammed; (V) Data analysis and interpretation: C Gwam, N Mohammed; (VI) Manuscript writing: All authors; (VII) Final approval of manuscript: All authors. Correspondence to: Chukwuweike Gwam, MD, MBA. Department of Orthopedic Surgery, Wake Forest School of Medicine, Wake Forest Baptist Medical Center, Medical Center Boulevard, Winston-Salem, NC 27157, USA. Email: [email protected]. Abstract: Regenerative medicine is a field growing in popularity due to high hopes for stimulating in situ tissue restoration. Stem cell therapy remain at the center of regenerative medicine, due to early reports on its pluripotent differentiating capability. However, more recent reports suggest the paracrine activity of stem cells, and not direct differentiation, as the cause of its therapeutic effects. This paracrine activity can be harnessed in the form of conditioned media. Despite these capabilities, the clinical translation of stem cell conditioned media (i.e., secretome) is precluded by a variety of factors. These limitations include standardization of stem cell-conditioned media formulation, characterization of bioactive factors in conditioned media and dosing, optimizing modes of delivery, and uncovering of mechanisms of action of stem cell conditioned media. The purpose of this review is to provide a focused narration on the aforementioned preclusions pertaining to the clinical translation of stem cell conditioned media.
    [Show full text]
  • Mesenchymal Stem Cell Secretome Reduces Pain and Prevents Cartilage Damage in a Murine Osteoarthritis Model
    EuropeanS Khatab etCells al. and Materials Vol. 36 2018 (pages 218-230) MSC DOI: secretome 10.22203/eCM.v036a16 reduces pain and OA cartilage ISSN 1473-2262 damage MESENCHYMAL STEM CELL SECRETOME REDUCES PAIN AND PREVENTS CARTILAGE DAMAGE IN A MURINE OSTEOARTHRITIS MODEL S. Khatab1,2, G.J.V.M. van Osch1,3,*, N. Kops1, Y.M. Bastiaansen-Jenniskens1, P.K. Bos1, J.A.N. Verhaar1, M.R. Bernsen2 and G.M. van Buul1 1 Department of Orthopaedics, Erasmus MC, Rotterdam, the Netherlands 2 Department of Radiology and Nuclear Medicine, Erasmus MC, Rotterdam, the Netherlands 3 Department of Otorhinolaryngology, Erasmus MC, Rotterdam, the Netherlands Abstract Mesenchymal stem cells (MSCs) represent a promising biological therapeutic option as an osteoarthritis (OA)-modifying treatment. MSCs secrete factors that can counteract inflammatory and catabolic processes and attract endogenous repair cells. The effects of intra-articular injection of MSC secretome on OA-related pain, cartilage damage, subchondral bone alterations and synovial inflammation were studied in a mouse collagenase-induced OA model. The MSC secretome was generated by stimulating human bone-marrow- derived MSCs with interferon gamma (IFNγ) and tumour necrosis factor alpha (TNFα). 54 mice were randomly assigned to injections with i) MSC secretome from 20,000 MSCs, ii) 20,000 MSCs or iii) medium (control). Pain was assessed by hind limb weight distribution. Cartilage damage, subchondral bone volume and synovial inflammation were evaluated by histology. MSC-secretome- and MSC-injected mice showed pain reduction at day 7 when compared to control mice. Cartilage damage was more abundant in the control group as compared to healthy knees, a difference which was not found in knees treated with MSC secretome or MSCs.
    [Show full text]