Article
Biotechnology & Applied Microbiology
Pascal Fichtel, Malte von Bonin, Robert Kuhnert, Kristin Moebus, Martin Bornhaeuser, Manja Wobus
Summary: Aging of the hematopoietic system is characterized by an expansion of hematopoietic stem and progenitor cells (HSPCs) with reduced capacity for engraftment, self-renewal, and lymphoid differentiation, resulting in myeloid-biased hematopoiesis.
The communication between HSPCs and MSCs is mediated by direct cell-cell contacts or extracellular vesicles (EVs) that carry bioactive substances. Aging MSCs secrete fewer miRNAs, but aged MSC-EVs contain higher levels of specific miRNAs such as miR-29a and miR-34a. Young EVs enhance the cell number and viability of HSPCs, while aged MSC-EVs promote the differentiation of HSPCs into erythroid and erythroid-megakaryocytic progenitor cells. The therapeutic relevance of MSC-derived EVs in modulating HSPC characteristics needs further investigation.
FRONTIERS IN BIOENGINEERING AND BIOTECHNOLOGY
(2022)
Article
Cell & Tissue Engineering
Hua Shen, Ryan A. Lane
Summary: Achilles tendon rupture, a common sports-related injury, often leads to long-term pain and functional deficits. Previous studies have shown that extracellular vesicles from inflammation-primed adipose-derived stem cells (iEVs) can alleviate the early inflammatory response to tendon injury. This study aimed to investigate the mechanistic roles of iEVs in regulating the injury response of tendons and promoting regeneration.
Article
Biochemistry & Molecular Biology
Shih-Heng Chen, Zhi-Yu Chen, Ya-Hsuan Lin, Shih-Hsien Chen, Pang-Yun Chou, Huang-Kai Kao, Feng-Huei Lin
Summary: This study demonstrated that extracellular vesicles (EVs) derived from adipose-derived stem cells (ADSCs) significantly enhanced tendon regeneration by promoting proliferation and migration of tenocytes. Treatment with ADSC-EVs also improved the mechanical strength of repaired tendons, suggesting a potentially highly potent therapeutic strategy for tendon injuries.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Multidisciplinary Sciences
Shi-Cong Tao, Ji-Yan Huang, Zi-Xiang Li, Shi Zhan, Shang-Chun Guo
Summary: The study identified the downstream mechanism of H19 in promoting tendon regeneration through activation of the YAP pathway. Stable overexpression of H19 in TSPCs was achieved using CRISPR technology, leading to the production of H19-enriched sEVs. These findings offer a new method for tendon repair and highlight the potential of modularized sEV-based therapies in tendon regeneration.
Review
Cell Biology
Victor Lu, Maria Tennyson, James Zhang, Wasim Khan
Summary: This systematic review explored the use of MSC-EVs for tendon/ligament repair, showing that MSC-EV therapy can facilitate tendon/ligament healing. However, not all studies found improvements in every parameter, with weak evidence linking biomechanical alterations to functional improvement.
Review
Biochemistry & Molecular Biology
Giusi Alberti, Eleonora Russo, Simona Corrao, Rita Anzalone, Peter Kruzliak, Vitale Miceli, Pier Giulio Conaldi, Francesca Di Gaudio, Giampiero La Rocca
Summary: Extracellular vesicles (EVs) are one of the main mechanisms of communication between cells and the surrounding tissue or at distance. Recent studies have revealed the molecular composition and clinical indications of EVs derived from adult mesenchymal stromal cells (MSCs). These EVs maintain some of the properties of their parent cells and have important implications for cell-free therapies.
Article
Biochemistry & Molecular Biology
Yuta Hayashi, Dilimulati Yimiti, Yohei Sanada, Chenyang Ding, Takenori Omoto, Toshihiko Ogura, Tomoyuki Nakasa, Masakazu Ishikawa, Keiko Hiemori, Hiroaki Tateno, Shigeru Miyaki, Nobuo Adachi
Summary: The therapeutic potential of MSC-derived EVs for tissue repair is being explored. The study found that early passaged MSC-EVs accelerate Achilles tendon healing compared with senescent MSC-EVs. Glycans on MSC-EVs may be useful for quality control and isolation of therapeutic MSC-EVs in regenerative medicine.
Review
Biotechnology & Applied Microbiology
Daniel Quintero, Carlotta Perucca Orfei, Lee D. Kaplan, Laura de Girolamo, Thomas M. Best, Dimitrios Kouroupis
Summary: Tendinopathies are a common group of disorders characterized by pain, compromised function, and prolonged absence from activity. Traditional treatment options only provide temporary relief and do not fully repair the tendon. Stem cell-based therapies and cell-free approaches, such as extracellular vesicles, have shown promise in modifying the course of tendinopathies.
FRONTIERS IN BIOENGINEERING AND BIOTECHNOLOGY
(2023)
Article
Cell Biology
Enrico Ragni, Carlotta Perucca Orfei, Laura de Girolamo
Summary: Bone-marrow-derived mesenchymal stromal cells (BMSCs) have therapeutic potential in the treatment of osteoarthritis (OA). The secretome of BMSCs, including soluble mediators and extracellular vesicles (EVs), suppress immune response, attenuate inflammation, and promote cartilage repair. This study found that the molecules in the secretome can inhibit the activation of immune cells, reduce the production of OA-related inflammatory mediators, and promote cartilage protection.
Review
Pharmacology & Pharmacy
Pauline Po Yee Lui, Yung Tim Leung
Summary: This review discusses the general and tissue-specific considerations for manufacturing MSC-EVs for clinical translation in the treatment of tendon and ligament injuries, including GMP-compliant manufacturing and quality control, safety and efficacy issues, and compatibility with arthroscopy.
Article
Cell Biology
Cansu Gorgun, Chiara Africano, Maria Chiara Ciferri, Nadia Bertola, Daniele Reverberi, Rodolfo Quarto, Silvia Ravera, Roberta Tasso
Summary: This study demonstrates that EVs derived from MSCs preconditioned with hypoxia inflammatory cytokines can attenuate inflammaging and alleviate age-related inflammation and mitochondrial dysfunction.
Review
Biochemistry & Molecular Biology
Ying Zhu, Zhao-Fu Liao, Miao-Hua Mo, Xing-Dong Xiong
Summary: Extracellular vesicles (EVs), including mesenchymal stromal cell-derived EVs (MSC-EVs), play crucial roles in cell-cell communication and have potential therapeutic applications in various vascular disorders. MSC-EVs have shown beneficial effects on angiogenesis and different vasculopathies such as atherosclerosis and vascular restenosis. Moreover, modified MSC-EVs and suitable biomaterials can further enhance their therapeutic effects. This review provides an overview of the functional roles of MSC-EVs in maintaining vascular homeostasis and discusses strategies to optimize their therapeutic applications.
Article
Multidisciplinary Sciences
Ni Su, Yaoyao Hao, Fang Wang, Wenda Hou, Haifeng Chen, Ying Luo
Summary: This study demonstrates that cell-mediated delivery of mesenchymal stromal exosomes onto biofunctional scaffolds can induce beneficial immune cell responses in mouse skin wounds. Additionally, active adaptive T helper cell responses were found in remote immune organs, and exosome-laden scaffolds facilitated tissue repair in large skin injury models.
Article
Biochemistry & Molecular Biology
Enrico Ragni, Carlotta Perucca Orfei, Marco Vigano, Federico Valli, Laura de Girolamo
Summary: Bone-marrow-derived stromal cells (BMSCs) are a promising therapeutic option for osteoarthritis (OA) due to their regenerative features. Extracellular vesicles (EVs) released by BMSCs contain miRNAs that play a crucial role in their therapeutic potential. This study aims to identify reliable reference genes (RGs) for studying miRNAs in BMSC-EVs cultured under standard or OA synovial fluid (OA-SF). The results suggest that miR-23a-3p and miR-221-3p are the best candidates, and miR-24-3p is the most stable RG for comparing EVs content.
Article
Medicine, Research & Experimental
Eman Mohamed Faruk, Wardah Abdullah Alasmari, Hanan Fouad, Ola Elsayed Nafea, Rehab Abd Allah Hasan
Summary: This study demonstrated the therapeutic potential of extracellular vesicles derived from bone marrow mesenchymal stem cells (BMSC-EVs) against fluoride-induced adrenal toxicity. BMSC-EVs effectively repaired damaged adrenal tissue and recovered its function following NaF consumption, reversing the toxic effects of fluoride and reprogramming injured adrenal cells by activating regenerative processes.
Article
Surgery
Nicola Maffulli, Marco Quaranta, Nicola Poeta, Francesco Oliva, Nat Padhiar, Otto Chan
Summary: The study evaluates the outcomes of minimally invasive fasciotomy in patients with symptomatic muscle herniae, specifically focusing on the tibialis anterior muscle. The results demonstrate that the surgery is effective and safe, leading to significant improvements in symptoms and a high rate of return to pre-injury or higher levels of sport/activity.
SURGEON-JOURNAL OF THE ROYAL COLLEGES OF SURGEONS OF EDINBURGH AND IRELAND
(2023)
Article
Surgery
Filippo Migliorini, Alice Baroncini, Jorg Eschweiler, Matthias Knobe, Markus Tingart, Nicola Maffulli
Summary: This study analyzed the rate of return to sport, related influencing factors, and sport activity level in patients with femoroacetabular impingement (FAI) using the Hip Outcome Score - Sport-Specific Subscale (HOS-SSS). The results showed that 88.75% of patients returned to sports within a mean of 37.4 months, and post-operative sport activity level was positively associated with lighter weight, younger age, and higher preoperative scores.
SURGEON-JOURNAL OF THE ROYAL COLLEGES OF SURGEONS OF EDINBURGH AND IRELAND
(2023)
Article
Surgery
Filippo Migliorini, Nicola Maffulli, Joerg Eschweiler, Hanno Schenker, Markus Tingart, Marcel Betsch
Summary: This meta-analysis compares the clinical outcomes of all-arthroscopic rotator cuff repair and mini-open surgery. The results show no significant differences in surgical duration, clinical scores, and functional outcomes between the two techniques. Male gender and older age are associated with higher rates of rotator cuff re-tears, while longer surgical duration is associated with a higher rate of adhesive capsulitis.
SURGEON-JOURNAL OF THE ROYAL COLLEGES OF SURGEONS OF EDINBURGH AND IRELAND
(2023)
Review
Medicine, General & Internal
Nicola Maffulli, Salvatore Ziello, Gianluca Maisto, Filippo Migliorini, Francesco Oliva
Summary: This study evaluated the outcome and complications of local tendon transfer procedures in patients with chronic Achilles tendon rupture. The use of FHL or PB tendon for local tendon transfer resulted in good clinical outcomes and a reliable return to daily activities and sports. However, the high rate of complications reflects the chronic nature of the condition and the technical complexity of the procedure.
JOURNAL OF CLINICAL MEDICINE
(2023)
Article
Cell Biology
Christoph Schmitz, Christopher Alt, Alon R. Azares, David A. Pearce, Tiffany R. Facile, John P. Furia, Nicola Maffulli, Claire Huang, Eckhard U. Alt
Summary: Uncultured, unmodified, autologous, adipose-derived regenerative cells (UA-ADRCs) are a safe and effective treatment option for various musculoskeletal pathologies. However, it is unknown whether the composition of the final cell suspension systematically varies with the subject's individual age, sex, body mass index and ethnicity.
Editorial Material
Orthopedics
Nicola Maffulli
CLINICAL ORTHOPAEDICS AND RELATED RESEARCH
(2023)
Editorial Material
Pathology
Annalisa Radeghieri, Paolo Bergese
EXPERT REVIEW OF MOLECULAR DIAGNOSTICS
(2023)
Article
Neurosciences
Andrea Casolo, Sumiaki Maeo, Thomas G. Balshaw, Marcel B. Lanza, Neil R. W. Martin, Stefano Nuccio, Tatiana Moro, Antonio Paoli, Francesco Felici, Nicola Maffulli, Bjoern Eskofier, Thomas M. Kinfe, Jonathan P. Folland, Dario Farina, Alessandro Del Vecchio
Summary: By combining non-invasive high-density surface EMG with muscle biopsy, the study investigated the relation between motor unit conduction velocity and muscle fibre diameter in the biceps brachii muscle. The results show the possibility of estimating muscle fibre size using conduction velocity estimates with low bias and individual error.
JOURNAL OF PHYSIOLOGY-LONDON
(2023)
Editorial Material
Orthopedics
Nicola Maffulli, Katarina Nilsson Helander, Filippo Migliorini
Summary: In both tendon repair and tendinopathy, symptoms may not align with the appearance of the affected tendon on imaging, suggesting a dissociation between morphology and symptoms. Asymptomatic abnormal findings have limited predictive value, and interventions based on imaging are inappropriate. Patient education and clinical monitoring are recommended. Planning interventions based on sonographic abnormalities in symptomatic tendinopathy may not be warranted. Current evidence is limited and caution is needed when interpreting incidental findings in athletes.
KNEE SURGERY SPORTS TRAUMATOLOGY ARTHROSCOPY
(2023)
Review
Chemistry, Medicinal
Francesco Melfi, Simone Carradori, Noemi Mencarelli, Cristina Campestre, Marialucia Gallorini, Silvia Di Giacomo, Antonella Di Sotto
Summary: This article provides a brief description of the anticancer potential of natural compounds, followed by a search for patents published from 2019 onwards according to the PRISMA guidelines. Additionally, relevant publications from the overall scientific literature were discussed.
EXPERT OPINION ON THERAPEUTIC PATENTS
(2023)
Article
Biochemistry & Molecular Biology
Marta Clerici, Vera Citro, Amy L. Byrne, Tina P. Dale, Aldo R. Boccaccini, Giovanna Della Porta, Nicola Maffulli, Nicholas R. Forsyth
Summary: By comparing and contrasting different tendon cell populations, this study found that type II tendon stem cells (TSCs) are the most promising population for expansion due to their enhanced proliferative potential, multipotency, and maintenance of a tendon-specific profile. Furthermore, physoxia promotes enhanced proliferation and maintenance of a tenogenic profile in all tendon-derived cell populations.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Sport Sciences
Mohamed Amine Ltifi, Mohamed Chedly Jlid, Jeremy Coquart, Nicola Maffulli, Roland van den Tillaar, Ridha Aouadi
Summary: This study compared the effects of different stretching methods on change of direction (COD) ability in soccer players. The results showed that dynamic stretching exercises improved COD, while other forms of stretching, particularly static stretching, negatively impacted COD performance. Coaches can consider integrating dynamic stretching protocols tailored to the athletes' specific needs.
Article
Chemistry, Multidisciplinary
Angelo Musico, Rossella Zenatelli, Miriam Romano, Andrea Zendrini, Silvia Alacqua, Selene Tassoni, Lucia Paolini, Chiara Urbinati, Marco Rusnati, Paolo Bergese, Giuseppe Pomarico, Annalisa Radeghieri
Summary: For successful medical application, nanosized systems need to have biocompatibility, targeting ability, immune system evasion, and resistance to clearance. Biogenic nanoparticles, such as extracellular vesicles (EVs), are being intensively studied as a platform that naturally possesses these crucial characteristics. This work explores and compares the functionalization of EVs with specific antibodies using chemisorption and physisorption methods, and reveals that the chemisorption method results in superior binding and uptake towards target cells, likely due to the stronger attachment.
NANOSCALE ADVANCES
(2023)
Article
Chemistry, Analytical
Karl Normak, Marcell Papp, Michael Ullmann, Carolina Paganini, Mauro Manno, Antonella Bongiovanni, Paolo Bergese, Paolo Arosio
Summary: This study demonstrates that liquid chromatography combined with multi-angle light scattering (MALS) and fluorescence detection can provide multiparametric characterization of extracellular vesicles (EVs) in one single apparatus. The method allows for analysis of EV concentration, average diameter, protein amount to particle number ratio, presence of surface markers and lipids, EV shape, and sample purity. It is fully automatable and can be applied to both crude and purified samples with limited sample handling and data analysis time.
ANALYTICAL CHEMISTRY
(2023)
Article
Multidisciplinary Sciences
Mark Lundeen, Jason L. Hurd, Matthew Hayes, Meredith Hayes, Tiffany R. Facile, John P. Furia, Nicola Maffulli, Christopher Alt, Eckhard U. Alt, Christoph Schmitz, David A. Pearce
Summary: This study found that the use of UA-ADRCs injections for sPTRCT treatment is more effective than corticosteroid injections in the long run and carries no greater risks. Subjects in the UA-ADRCs group showed significantly higher ASES Total scores.
SCIENTIFIC REPORTS
(2023)
