Review
Cell & Tissue Engineering
Zeinab Shirbaghaee, Mohammad Hassani, Saeed Heidari Keshel, Masoud Soleimani
Summary: This article reviews the immunomodulatory features of mesenchymal stem cells (MSCs) and their potential applications as therapeutic agents in the treatment of critical limb ischemia (CLI). Despite advances in clinical research, MSC therapy is still considered experimental and not recommended for regular clinical use. The article provides recommendations to improve the efficacy of cell therapy for CLI patients.
STEM CELL RESEARCH & THERAPY
(2022)
Article
Cell & Tissue Engineering
Pegah Nammian, Seyedeh-Leili Asadi-Yousefabad, Sajad Daneshi, Mohammad Hasan Sheikhha, Seyed Mohammad Bagher Tabei, Vahid Razban
Summary: The study compared the effects of allogeneic bone marrow mesenchymal stem cells (BM-MSCs) and adipose tissue mesenchymal stem cells (AT-MSCs) in the treatment of critical limb ischemia (CLI). The results indicated that BM-MSCs had a stronger effect on endothelial cell migration, muscle restructure, functional improvements, and neovascularization in ischemic tissues compared to AT-MSCs. This suggests that BM-MSC transplantation could be a more effective therapy for diseases with insufficient angiogenesis, such as hindlimb ischemia.
STEM CELL RESEARCH & THERAPY
(2021)
Article
Engineering, Biomedical
Corinne W. Curry, Sarah M. Sturgeon, Brian J. O. 'Grady, Alexis Yates, Andrew Kjar, Hayden Paige, Lucas S. Mowery, Ketaki A. Katdare, Riya Patel, Kate Mlouk, Madison R. Stiefbold, Sidney Vafaie-Partin, Atsuyuki Kawabata, Rachel Mckee, Stephanie Moore-Lotridge, Adrienne Hawkes, Jiro Kusunose, Katherine N. Gibson-Corley, Jeffrey Schmeckpeper, Jonathan G. Schoenecker, Charles F. Caskey, Ethan S. Lippmann
Summary: Researchers have found that a gelatin-based hydrogel without growth factors or encapsulated cells can promote arteriogenesis and reduce tissue damage in a model of critical limb ischemia. The hydrogel recruits smooth muscle cells to vessel structures, restoring limb perfusion and maintaining tissue health for up to 14 days in mice.
Article
Cell & Tissue Engineering
Darwin Eton, Guolin Zhou, Tong-Chuan He, Amelia Bartholomew, Rachana Patil
Summary: In patients with chronic limb-threatening ischemia (CLTI), the use of Filgrastim and a programmed compression pump (PCP) can lead to segmental recanalization of occluded arteries. Molecular evidence suggests fibrinolysis and neovascularization as potential mechanisms for this effect. Further clinical testing is needed to validate these findings and explore the potential use of this treatment in other chronic ischemic conditions.
JOURNAL OF TISSUE ENGINEERING AND REGENERATIVE MEDICINE
(2022)
Article
Cardiac & Cardiovascular Systems
Wahiba Dhahri, Sylvie Dussault, Nozha Raguema, Michel Desjarlais, Alain Rivard
Summary: This study found that Riociguat, an sGC stimulator, promotes angiogenesis and improves neovascularization after ischemia. The mechanism involves the activation of the p44/p42 MAP kinase pathway and an increase in the number and functions of PACs. This discovery could potentially serve as a new therapeutic strategy for reducing tissue ischemia in patients with severe atherosclerotic diseases.
Article
Medicine, General & Internal
Florian Simon, Mansur Duran, Waseem Garabet, Hubert Schelzig, Michael Jacobs, Alexander Gombert
Summary: A decade ago, gene therapy was seen as a potential treatment for chronic limb-threatening ischemia, but its safety and clinical feasibility are still in question. Gene therapy can be achieved through transduction and transfection methods, but there are risks involved, such as increased neo-vascularization in undesired tissue, malignant transformation and inflammation, and arterial thrombosis. Clinical trials of gene therapy in vascular occlusive disease have shown mixed results, leaving the role of gene therapy unclear.
JOURNAL OF CLINICAL MEDICINE
(2022)
Review
Engineering, Biomedical
Zheng Xing, Chen Zhao, Siwen Wu, Chunchen Zhang, Haifeng Liu, Yubo Fan
Summary: Therapeutic angiogenesis provides a potential solution for critical limb ischemia by manipulating blood vessel growth in vivo without the need for extra pharmaceutics and surgery. With the rise of interdisciplinary research, regenerative medicine strategies offer new possibilities for treating various clinical diseases.
Article
Engineering, Biomedical
Grazia Marsico, Chunseng Jin, Sunny A. Abbah, Eva M. Brauchle, Dilip Thomas, Ana Lucia Rebelo, Doriana Orbanic, Sandrine Chantepie, Paolo Contessotto, Dulce Papy-Garcia, Carlos Rodriguez-Cabello, Michelle Kilcoyne, K. Schenke-Layland, N. G. Karlsson, Karl J. A. McCullagh, Abhay Pandit
Summary: This study demonstrated glycosylation changes associated with ischemia in a murine CLI model, and evaluated the efficacy of an ELR hydrogel for CLI treatment. The ELR hydrogel modulated angiogenic signaling pathways, promoted capillary formation and ECM remodeling, while also inducing arterioles formation, reducing fibrosis, and polarizing anti-inflammatory macrophages. The study suggests a potential role for mannosylation and sialylation in tissue repair, highlighting glycosylation alterations as new therapeutic targets for CLI.
Article
Cardiac & Cardiovascular Systems
Lirong Xu, Yutong Liu, Qianyun Cheng, Yang Shen, Ye Yuan, Xiaolang Jiang, Xu Li, Daqiao Guo, Junhao Jiang, Changpo Lin
Summary: CLI, the most advanced clinical stage of peripheral vascular disease, leads to lower extremity rest pain, ulceration, and gangrene due to insufficient blood and oxygen supply, making effective biomarkers and therapeutic targets crucial. The study confirmed the downregulation of circadian gene Bmal1 in CLI patients, affecting inflammation and angiogenesis. Bmal1 disruption impairs angiogenesis and endothelial cell functions, suggesting its potential as a biomarker and therapeutic target in CLI.
FRONTIERS IN CARDIOVASCULAR MEDICINE
(2021)
Article
Cardiac & Cardiovascular Systems
Lirong Xu, Yutong Liu, Qianyun Cheng, Yang Shen, Ye Yuan, Xiaolang Jiang, Xu Li, Daqiao Guo, Junhao Jiang, Changpo Lin
Summary: CLI, the most advanced stage of peripheral vascular disease, involves downregulation of circadian gene Bmal1 which affects lipid metabolism, inflammation, and angiogenesis. This downregulation impairs angiogenesis and endothelial cell functions, while repressing inflammation and promoting angiogenesis through transcriptional regulation of VEGF. Therefore, Bmal1 may serve as an effective biomarker and therapeutic target in CLI.
FRONTIERS IN CARDIOVASCULAR MEDICINE
(2021)
Review
Endocrinology & Metabolism
Yue Cai, Guang-Yao Zang, Yan Huang, Zhen Sun, Li-Li Zhang, Yong-Jiang Qian, Wei Yuan, Zhong-Qun Wang
Summary: With the high incidence of diabetes around the world, neovascularization plays a significant role in its development. This review introduces the mechanisms of neovascularization after diabetic ischemia, aiming to increase understanding of diabetic ischemic complications and provide more treatment options for clinical practice. The study found that factors such as mononuclear macrophage migration, cytokine secretion, and signaling pathway activation promote the formation of new blood vessels and restore blood supply.
WORLD JOURNAL OF DIABETES
(2022)
Review
Dermatology
Daniel Bormann, Alfred Gugerell, Hendrik Jan Ankersmit, Michael Mildner
Summary: Cell secretomes play an important role in wound healing by promoting regeneration. This study reviews the mechanisms of action of cell secretomes in wound healing, important preconditioning strategies to enhance therapeutic efficacy, and clinical trials on secretome-based wound healing.
JOURNAL OF INVESTIGATIVE DERMATOLOGY
(2023)
Article
Biochemistry & Molecular Biology
Lucia Beltran-Camacho, Margarita Jimenez-Palomares, Ismael Sanchez-Gomar, Antonio Rosal-Vela, Marta Rojas-Torres, Sara Eslava-Alcon, Jose Angel Alonso-Pinero, Almudena Gonzalez-Rovira, Ma Jesus Extremera-Garcia, Rosario Conejero, Esther Doiz, Manuel Rodriguez-Pinero, Martin R. Larsen, Ma Carmen Duran-Ruiz
Summary: The study suggests that circulating angiogenic cells (CACs) have regenerative potential and can enhance blood flow recovery in mice with critical limb ischemia. Pre-stimulation of CACs with factors secreted by atherosclerotic plaques enhances their regenerative properties. Proteomics analysis identified potential proteins involved in the response to ischemia and the effect of CACs administration, indicating a possible mechanism for the therapeutic effects of CACs in CLI.
Article
Immunology
Christian Kupatt, Tilman Ziegler, Andrea Baehr, Ferdinand Le Noble
Summary: Current clinical revascularization techniques for coronary or peripheral artery disease mainly focus on large vessels of the heart, neglecting the microcirculatory compartment. However, cardiovascular risk factors not only lead to large vessel atherosclerosis, but also cause microcirculatory rarefaction, which is not effectively addressed by current therapies. This review discusses the potential of angiogenic gene therapy to reverse capillary rarefaction, provided that disease-causing inflammation and vessel-destabilization are targeted. Additionally, the role of Thymosin ss4 (Tss4) and its downstream signal, myocardin-related transcription factor-A (MRTF-A), in counteracting capillary rarefaction is explored.
INTERNATIONAL IMMUNOPHARMACOLOGY
(2023)
Review
Genetics & Heredity
Vyacheslav Z. Tarantul, Alexander Gavrilenko
Summary: Peripheral artery diseases are a serious public health problem. This review focuses on gene therapy as an alternative and potentially more effective treatment option for no-option patients. The review presents the results of many years of research and application of gene therapy as a treatment for patients with critical limb ischemia, including successful and unsuccessful attempts. The review also highlights trends in changing approaches to therapeutic angiogenesis.
CURRENT GENE THERAPY
(2022)
Article
Biochemistry & Molecular Biology
Lucia Beltran-Camacho, Sara Eslava-Alcon, Marta Rojas-Torres, Daniel Sanchez-Morillo, Ma Pilar Martinez-Nicolas, Victoria Martin-Bermejo, Ines Garcia de la Torre, Esther Berrocoso, Juan Antonio Moreno, Rafael Moreno-Luna, Ma Carmen Duran-Ruiz
Summary: This study evaluated the impact of serum from asymptomatic COVID-19 individuals on circulating angiogenic cells (CACs) using a proteomics-based quantitative approach. The results confirmed that SARS-CoV-2 infection in asymptomatic individuals caused protein level changes related to coagulation and inflammatory processes. Additionally, certain proteins were up-regulated only in CACs treated with serum from asymptomatic patients during the highest peak of infection. These findings provide insight into the effects of SARS-CoV-2 infection and the development of potential treatment methods.
MOLECULAR MEDICINE
(2022)
Article
Cell Biology
Mario Martinez-Torija, Pedro F. Esteban, Francisco Javier Espino-Rodriguez, Beatriz Paniagua-Torija, Eduardo Molina-Holgado, Silvia Ceruelo, Gemma Barroso-Garcia, Alba G. Arandilla, Luis F. Lopez-Almodovar, Angel Arevalo-Martin, Juan Antonio Moreno, Daniel Garcia-Ovejero, M. Carmen Duran-Ruiz, Rafael Moreno-Luna
Summary: The risk of complications following surgical procedures is significantly increased in patients with SARS-CoV-2 infection. This study found that SCI patients with a COVID-19-positive diagnosis showed worse recovery and severe postoperative complications. Proteomic analysis revealed several upregulated proteins in the adipose tissue surrounding the ulcers. Among them, CKMT2 and CKM stood out and increased after the COVID-19 diagnosis. These proteins were largely found in MGCs within the adipose tissue. The presence of CKMT2, CKM, and MGCs may serve as predictive biomarkers of postsurgical complications in post-COVID patients.
Article
Biochemistry & Molecular Biology
Ismael Sanchez-Gomar, Josefa Benitez-Camacho, Cristina Cejudo-Bastante, Lourdes Casas, Rafael Moreno-Luna, Casimiro Mantell, Ma Carmen Duran-Ruiz
Summary: The study evaluated the potential of mango leaves, olive leaves, and red grape pomace extracts rich in polyphenols to promote ECFC reparative effects. It was found that ethanolic extracts at low concentrations improved angiogenic capacities of ECFCs and reduced proliferation, apoptosis, and the inflammatory response of these cells.
Article
Cell & Tissue Engineering
Marta Rojas-Torres, Ismael Sanchez-Gomar, Antonio Rosal-Vela, Lucia Beltran-Camacho, Sara Eslava-Alcon, Jose Angel Alonso-Pineiro, Javier Martin-Ramirez, Rafael Moreno-Luna, Ma Carmen Duran-Ruiz
Summary: Before translating ECFCs into clinical treatment, it is necessary to perform biodistribution assays to ensure biosafety and determine the distribution of cells. This study optimized a cell-tracking assay using DiR labeling and qPCR analysis, and found that intramuscularly administered ECFCs mainly remained in the ischemic tissues, while intravenously injected cells were found in multiple organs.
STEM CELL RESEARCH & THERAPY
(2022)
Article
Polymer Science
Pilar Grosso, Cristina Cejudo, Ismael Sanchez-Gomar, M. Carmen Duran-Ruiz, Rafael Moreno-Luna, Lourdes Casas, Clara Pereyra, Casimiro Mantell
Summary: The addition of natural substances with pharmacoactive properties to polymeric biomedical devices can enhance the assimilation of these implants and promote blood vessel formation. In this study, mango leaf extract (MLE) obtained through pressurized ethanol was impregnated into polylactic acid (PLA) devices. The best impregnation conditions and results were determined through in vitro culture experiments and microscopy observations.
Article
Biochemistry & Molecular Biology
Alvaro Gonzalez-Dominguez, Francisco Visiedo, Jesus Dominguez-Riscart, Ma Carmen Duran-Ruiz, Ana Saez-Benito, Alfonso M. Lechuga-Sancho, Rosa Maria Mateos
Summary: In children with obesity and insulin resistance, the activity of erythrocyte catalase is impaired due to increased S-nitrosation of the enzyme. Other post-translational modifications (PTMs) such as O-glycosylation, tyrosine nitration, and S-glutathionylation were also observed in erythrocyte catalase, but levels of O-glycosylation and S-glutathionylation were reduced in the ObIR+ group.
FREE RADICAL BIOLOGY AND MEDICINE
(2022)
Article
Medicine, Research & Experimental
Maria Calderon-Dominguez, Eva Trejo-Gutierrez, Almudena Gonzalez-Rovira, Lucia Beltran-Camacho, Marta Rojas-Torres, Sara Eslava-Alcon, Daniel Sanchez-Morillo, Juan Calderon-Dominguez, Ma Pilar Martinez-Nicolas, Estibaliz Gonzalez-Beitia, Ma Dolores Nieto-Martin, Teresa Trujillo-Soto, Manuel A. Rodriguez-Iglesias, Juan A. Moreno, Rafael Moreno-Luna, Ma Carmen Duran-Ruiz
Summary: Studies have shown that SARS-CoV-2 infection can alter the levels of microRNAs, which target key proteins involved in disease severity and progression. These findings provide potential biomarkers for COVID-19 and offer candidates for future therapeutic approaches against the disease.
MOLECULAR THERAPY-NUCLEIC ACIDS
(2022)
Article
Biology
Alejandra Sanchez-Brinas, Carmen Duran-Ruiz, Antonio Astola, Marta Marina Arroyo, Fatima G. Raposo, Antonio Valle, Jorge Bolivar
Summary: Research reveals that NOA36 interacts with HSPA1 and HSPA8 heat shock proteins, and plays a crucial role in cell proliferation and cell cycle.
Article
Biochemistry & Molecular Biology
Diego Valor, Antonio Montes, Maria Calderon-Dominguez, Inass Aghziel, Ismael Sanchez-Gomar, Martin Alcala, Ma Carmen Duran-Ruiz, Clara Pereyra
Summary: Submicron particles were produced from an ethanolic extract of Myrtus communnis leaves using supercritical carbon dioxide technology. The particles had small sizes, quasi-spherical shape, and high antioxidant activity. It was also observed that increasing pressure and temperature resulted in smaller particle sizes.
Article
Biochemistry & Molecular Biology
Lucia Beltran-Camacho, Santosh D. Bhosale, Daniel Sanchez-Morillo, Ismael Sanchez-Gomar, Marta Rojas-Torres, Sara Eslava-Alcon, Mario Martinez-Torija, M. Angeles Ruiz de Infante, M. Dolores Nieto-Martin, Manuel A. Rodriguez-Iglesias, Juan A. Moreno, Esther Berrocoso, Martin R. Larsen, Rafael Moreno-Luna, M. Carmen Duran-Ruiz
Summary: SARS-CoV-2 infection affects the cardiovascular system, causing vascular damage and thromboembolic events. Endothelial dysfunction is an early response to COVID-19, which may lead to cardiovascular complications and long-term sequelae. However, the molecular mechanisms involved in these processes remain poorly understood.
INTERNATIONAL JOURNAL OF BIOLOGICAL SCIENCES
(2023)