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Jiang Z, Huang C, Guo E, Zhu X, Li N, Huang Y, Wang P, Shan H, Yin Y, Wang H, Huang L, Han Z, Ouyang K, Sun L. Platelet-Rich Plasma in Young and Elderly Humans Exhibits a Different Proteomic Profile. J Proteome Res 2024; 23:1788-1800. [PMID: 38619924 DOI: 10.1021/acs.jproteome.4c00030] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 04/17/2024]
Abstract
As people age, their ability to resist injury and repair damage decreases significantly. Platelet-rich plasma (PRP) has demonstrated diverse therapeutic effects on tissue repair. However, the inconsistency of patient outcomes poses a challenge to the practical application of PRP in clinical practice. Furthermore, a comprehensive understanding of the specific impact of aging on PRP requires a systematic investigation. We derived PRP from 6 young volunteers and 6 elderly volunteers, respectively. Subsequently, 95% of high-abundance proteins were removed, followed by mass spectrometry analysis. Data are available via ProteomeXchange with the identifier PXD050061. We detected a total of 739 proteins and selected 311 proteins that showed significant differences, including 76 upregulated proteins in the young group and 235 upregulated proteins in the elderly group. Functional annotation and enrichment analysis unveiled upregulation of proteins associated with cell apoptosis, angiogenesis, and complement and coagulation cascades in the elderly. Conversely, IGF1 was found to be upregulated in the young group, potentially serving as the central source of enhanced cell proliferation ability. Our investigation not only provides insights into standardizing PRP preparation but also offers novel strategies for augmenting the functionality of aging cells or tissues.
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Affiliation(s)
- Zhitong Jiang
- Department of Cardiovascular Surgery, Shenzhen Peking University-The Hong Kong University of Science and Technology Medical Center, Peking University Shenzhen Hospital, Shenzhen 518036, China
| | - Can Huang
- Department of Cardiovascular Surgery, Peking University Shenzhen Hospital, Shenzhen 518036, China
| | - Erliang Guo
- Department of Thoracic Surgery, Harbin Medical University Cancer Hospital, Harbin 150081, China
| | - Xiangbin Zhu
- Department of Cardiovascular Surgery, Peking University Shenzhen Hospital, Shenzhen 518036, China
| | - Na Li
- Department of Cardiovascular Surgery, Peking University Shenzhen Hospital, Shenzhen 518036, China
| | - Yu Huang
- Department of Cardiovascular Surgery, Peking University Shenzhen Hospital, Shenzhen 518036, China
| | - Peihe Wang
- Department of Cardiovascular Surgery, Peking University Shenzhen Hospital, Shenzhen 518036, China
| | - Hui Shan
- Institute of Precision Medicine, Peking University Shenzhen Hospital, Shenzhen 518036, China
| | - Yuxin Yin
- Institute of Precision Medicine, Peking University Shenzhen Hospital, Shenzhen 518036, China
| | - Hong Wang
- Central Laboratory, Peking University Shenzhen Hospital, Shenzhen 518036, China
| | - Lei Huang
- Department of Cardiovascular Surgery, Peking University Shenzhen Hospital, Shenzhen 518036, China
| | - Zhen Han
- Department of Cardiovascular Surgery, Peking University Shenzhen Hospital, Shenzhen 518036, China
| | - Kunfu Ouyang
- Department of Cardiovascular Surgery, Peking University Shenzhen Hospital, Shenzhen 518036, China
| | - Lu Sun
- Department of Cardiovascular Surgery, Peking University Shenzhen Hospital, Shenzhen 518036, China
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Zheng H, Xu Y, Liehn EA, Rusu M. Vitamin C as Scavenger of Reactive Oxygen Species during Healing after Myocardial Infarction. Int J Mol Sci 2024; 25:3114. [PMID: 38542087 PMCID: PMC10970003 DOI: 10.3390/ijms25063114] [Citation(s) in RCA: 1] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/17/2023] [Revised: 01/31/2024] [Accepted: 02/10/2024] [Indexed: 06/26/2024] Open
Abstract
Currently, coronary artery bypass and reperfusion therapies are considered the gold standard in long-term treatments to restore heart function after acute myocardial infarction. As a drawback of these restoring strategies, reperfusion after an ischemic insult and sudden oxygen exposure lead to the exacerbated synthesis of additional reactive oxidative species and the persistence of increased oxidation levels. Attempts based on antioxidant treatment have failed to achieve an effective therapy for cardiovascular disease patients. The controversial use of vitamin C as an antioxidant in clinical practice is comprehensively systematized and discussed in this review. The dose-dependent adsorption and release kinetics mechanism of vitamin C is complex; however, this review may provide a holistic perspective on its potential as a preventive supplement and/or for combined precise and targeted therapeutics in cardiovascular management therapy.
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Affiliation(s)
- Huabo Zheng
- Department of Cardiology, Angiology and Intensive Care, University Hospital, Rheinisch-Westfälische Technische Hochschule Aachen University, 52074 Aachen, Germany;
- Institute of Molecular Medicine, University of Southern Denmark, Campusvej 55, 5230 Odense, Denmark;
| | - Yichen Xu
- Institute of Molecular Medicine, University of Southern Denmark, Campusvej 55, 5230 Odense, Denmark;
- Department of Histology and Embryology, Medicine and Life Sciences, Hainan Medical University, Haikou 571199, China
| | - Elisa A. Liehn
- Institute of Molecular Medicine, University of Southern Denmark, Campusvej 55, 5230 Odense, Denmark;
- National Institute of Pathology “Victor Babes”, Splaiul Independentei Nr. 99-101, 050096 Bucharest, Romania
| | - Mihaela Rusu
- Institute of Applied Medical Engineering, Helmholtz Institute, Medical Faculty, Rheinisch-Westfälische Technische Hochschule Aachen University, 52074 Aachen, Germany
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Gao H, Liu S, Qin S, Yang J, Yue T, Ye B, Tang Y, Feng J, Hou J, Danzeng D. Injectable hydrogel-based combination therapy for myocardial infarction: a systematic review and Meta-analysis of preclinical trials. BMC Cardiovasc Disord 2024; 24:119. [PMID: 38383333 PMCID: PMC10882925 DOI: 10.1186/s12872-024-03742-0] [Citation(s) in RCA: 8] [Impact Index Per Article: 8.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/30/2023] [Accepted: 01/19/2024] [Indexed: 02/23/2024] Open
Abstract
INTRODUCTION This study evaluates the effectiveness of a combined regimen involving injectable hydrogels for the treatment of experimental myocardial infarction. PATIENT CONCERNS Myocardial infarction is an acute illness that negatively affects quality of life and increases mortality rates. Experimental models of myocardial infarction can aid in disease research by allowing for the development of therapies that effectively manage disease progression and promote tissue repair. DIAGNOSIS Experimental animal models of myocardial infarction were established using the ligation method on the anterior descending branch of the left coronary artery (LAD). INTERVENTIONS The efficacy of intracardiac injection of hydrogels, combined with cells, drugs, cytokines, extracellular vesicles, or nucleic acid therapies, was evaluated to assess the functional and morphological improvements in the post-infarction heart achieved through the combined hydrogel regimen. OUTCOMES A literature review was conducted using PubMed, Web of Science, Scopus, and Cochrane databases. A total of 83 papers, including studies on 1332 experimental animals (rats, mice, rabbits, sheep, and pigs), were included in the meta-analysis based on the inclusion and exclusion criteria. The overall effect size observed in the group receiving combined hydrogel therapy, compared to the group receiving hydrogel treatment alone, resulted in an ejection fraction (EF) improvement of 8.87% [95% confidence interval (CI): 7.53, 10.21] and a fractional shortening (FS) improvement of 6.31% [95% CI: 5.94, 6.67] in rat models, while in mice models, the improvements were 16.45% [95% CI: 11.29, 21.61] for EF and 5.68% [95% CI: 5.15, 6.22] for FS. The most significant improvements in EF (rats: MD = 9.63% [95% CI: 4.02, 15.23]; mice: MD = 23.93% [95% CI: 17.52, 30.84]) and FS (rats: MD = 8.55% [95% CI: 2.54, 14.56]; mice: MD = 5.68% [95% CI: 5.15, 6.22]) were observed when extracellular vesicle therapy was used. Although there have been significant results in large animal experiments, the number of studies conducted in this area is limited. CONCLUSION The present study demonstrates that combining hydrogel with other therapies effectively improves heart function and morphology. Further preclinical research using large animal models is necessary for additional study and validation.
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Affiliation(s)
- Han Gao
- School of Medicine, Tibet University, Lhasa, Tibet, China
| | - Song Liu
- School of Medicine, Tibet University, Lhasa, Tibet, China
| | - Shanshan Qin
- School of Medicine, Tibet University, Lhasa, Tibet, China
| | - Jiali Yang
- School of Life Science and Engineering, Southwest Jiaotong University, Chengdu, Sichuan, China
| | - Tian Yue
- School of Life Science and Engineering, Southwest Jiaotong University, Chengdu, Sichuan, China
| | - Bengui Ye
- West China School of Pharmacy, Sichuan University, Chengdu, Sichuan, China
| | - Yue Tang
- School of Pharmacy, North Sichuan Medical College, Nanchong, Sichuan, China
| | - Jie Feng
- School of Medicine, Southwest Jiaotong University, Chengdu, Sichuan, China
| | - Jun Hou
- Department of Cardiology, Chengdu Third People's Hospital, Chengdu, Sichuan, China.
| | - Dunzhu Danzeng
- School of Medicine, Tibet University, Lhasa, Tibet, China.
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Wei X, Chen K, Huang C, Zhou K, Wang R, Wang Y, Xiao Y. Effect of autologous platelet-rich plasma on patients with acute type A aortic dissection underwent aortic arch replacement: A retrospective cohort study. PLoS One 2023; 18:e0290384. [PMID: 37590313 PMCID: PMC10434921 DOI: 10.1371/journal.pone.0290384] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/16/2023] [Accepted: 08/07/2023] [Indexed: 08/19/2023] Open
Abstract
BACKGROUND Coagulopathy and massive bleeding are common complications of patients with Stanford type A acute aortic dissection repair, and patients with these complications require many transfusions. Autologous platelet-rich plasma (PRP) is widely used to reduce the need for blood products. In the present study, we aimed to investigate the effects of PRP on blood conservation and the postoperative conditions of patients who underwent aortic arch replacement. METHODS Patients with aortic dissection undergoing aortic arch replacement were included initially application In all, 837 patients were divided into the PRP and non-PRP groups according to PRP use, whereupon a propensity score match was performed. The data analyzed included patient basic information, intraoperative information, postoperative biochemical examinations, and CTA reports. RESULTS In total, 610 patients were finally included (305 patients per group). Groups were well balanced after matching. Compared to the non-PRP group, less cryoprecipitate was transfused in the PRP group (10.0 [7.5, 11.0] vs. 10.0 [10.0, 11.5], P = 0.021), while no differences were found in packed RBC, FFP, and platelets between the two groups. Also, the surgery variables showed no differences. After surgery, patients in the PRP group showed higher postoperative serum albumin (36.43±4.20 vs. 35.39±4.40 g/L, P = 0.004) and total protein levels (59.38±6.25 vs. 58.06±7.19 g/L, P = 0.019) than the non-PRP group, but no significant differences in the levels of ALT, AST, Scr, and BUN. CTA reports showed that the proportion of patients with pleural effusion was lower in the PRP group (76.66% vs. 83.99%, OR = 1.59, 95% CI: 1.04-2.45, P = 0.028), while the proportions of pericardial effusion were not significantly different. CONCLUSIONS PRP application in aortic arch replacement surgery reduced the transfusion of cryoprecipitate, increased the postoperative serum albumin and total protein levels, and reduced the incidence of pleural effusion. No effect of PRP application was found on other postoperative blood indicators and CTA reports.
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Affiliation(s)
- Xiaojin Wei
- Department of Pain Management and Anesthesiology, The Second Xiangya Hospital, Central South University, Changsha, Hunan, China
| | - Kai Chen
- Department of Pain Management and Anesthesiology, The Second Xiangya Hospital, Central South University, Changsha, Hunan, China
| | - Chaodong Huang
- Department of Pain Management and Anesthesiology, The Second Xiangya Hospital, Central South University, Changsha, Hunan, China
- Department of Pain, Guizhou Provincial People’s Hospital, Guiyang, Guizhou, China
| | - Kang Zhou
- Department of Cardiovascular Surgery, The Second Xiangya Hospital, Central South University, Changsha, Hunan, China
| | - Ruixuan Wang
- Bourns Engineering, The University of California, Riverside, Riverside, CA, United States of America
| | - Yaping Wang
- Department of Pain Management and Anesthesiology, The Second Xiangya Hospital, Central South University, Changsha, Hunan, China
| | - Yanying Xiao
- Department of Pain Management and Anesthesiology, The Second Xiangya Hospital, Central South University, Changsha, Hunan, China
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Hu W, Yang C, Guo X, Wu Y, Loh XJ, Li Z, Wu YL, Wu C. Research Advances of Injectable Functional Hydrogel Materials in the Treatment of Myocardial Infarction. Gels 2022; 8:423. [PMID: 35877508 PMCID: PMC9316750 DOI: 10.3390/gels8070423] [Citation(s) in RCA: 12] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/31/2022] [Revised: 06/30/2022] [Accepted: 07/03/2022] [Indexed: 12/10/2022] Open
Abstract
Myocardial infarction (MI) has become one of the serious diseases threatening human life and health. However, traditional treatment methods for MI have some limitations, such as irreversible myocardial necrosis and cardiac dysfunction. Fortunately, recent endeavors have shown that hydrogel materials can effectively prevent negative remodeling of the heart and improve the heart function and long-term prognosis of patients with MI due to their good biocompatibility, mechanical properties, and electrical conductivity. Therefore, this review aims to summarize the research progress of injectable hydrogel in the treatment of MI in recent years and to introduce the rational design of injectable hydrogels in myocardial repair. Finally, the potential challenges and perspectives of injectable hydrogel in this field will be discussed, in order to provide theoretical guidance for the development of new and effective treatment strategies for MI.
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Affiliation(s)
- Wei Hu
- Fujian Provincial Key Laboratory of Innovative Drug Target Research and State Key Laboratory of Cellular Stress Biology, School of Pharmaceutical Sciences, Xiamen University, Xiamen 361102, China; (W.H.); (X.G.); (Y.W.)
| | - Cui Yang
- School of Medicine, Xiamen University, Xiamen 361003, China;
| | - Xiaodan Guo
- Fujian Provincial Key Laboratory of Innovative Drug Target Research and State Key Laboratory of Cellular Stress Biology, School of Pharmaceutical Sciences, Xiamen University, Xiamen 361102, China; (W.H.); (X.G.); (Y.W.)
| | - Yihong Wu
- Fujian Provincial Key Laboratory of Innovative Drug Target Research and State Key Laboratory of Cellular Stress Biology, School of Pharmaceutical Sciences, Xiamen University, Xiamen 361102, China; (W.H.); (X.G.); (Y.W.)
| | - Xian Jun Loh
- Institute of Materials Research and Engineering (IMRE), Agency for Science, Technology and Research (A*STAR), Singapore 138634, Singapore;
| | - Zibiao Li
- Institute of Materials Research and Engineering (IMRE), Agency for Science, Technology and Research (A*STAR), Singapore 138634, Singapore;
- Institute of Sustainability for Chemicals, Energy and Environment (ISCE) Agency for Science, Technology and Research (A*STAR), Singapore 138634, Singapore
- Department of Materials Science and Engineering, National University of Singapore, 9 Engineering Drive 1, Singapore 117576, Singapore
| | - Yun-Long Wu
- Fujian Provincial Key Laboratory of Innovative Drug Target Research and State Key Laboratory of Cellular Stress Biology, School of Pharmaceutical Sciences, Xiamen University, Xiamen 361102, China; (W.H.); (X.G.); (Y.W.)
| | - Caisheng Wu
- Fujian Provincial Key Laboratory of Innovative Drug Target Research and State Key Laboratory of Cellular Stress Biology, School of Pharmaceutical Sciences, Xiamen University, Xiamen 361102, China; (W.H.); (X.G.); (Y.W.)
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Imam SS, Al-Abbasi FA, Hosawi S, Afzal M, Nadeem MS, Ghoneim MM, Alshehri S, Alzarea SI, Alquraini A, Gupta G, Kazmi I. Role of platelet rich plasma mediated repair and regeneration of cell in early stage of cardiac injury. Regen Ther 2022; 19:144-153. [PMID: 35229012 PMCID: PMC8856949 DOI: 10.1016/j.reth.2022.01.006] [Citation(s) in RCA: 18] [Impact Index Per Article: 6.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/21/2021] [Revised: 01/18/2022] [Accepted: 01/27/2022] [Indexed: 12/12/2022] Open
Abstract
Platelet-rich plasma (PRP) is a widely accepted treatment approach and has heightened the quality of care among physicians. PRP has been used over the last decade to boost clinical results of plastic therapies, periodontal surgery and intra-bony defects. According to certain research, elevated levels of PRP growth factors that could promote tissue repair and have the potential for PRP to be beneficial in regenerating processes that Maxillofacial and Oral Surgeons, Veterinary Officers, Athletic medicine specialists and Dermatologists have long admired. PRP is an autologous whole blood fraction that has a heavy amount of a variety of growth factors such as epidermal growth factor (EGF), Vascular Endothelial Growth Factor (VEGF), hepatocyte growth factor (HGF), fibroblast growth factors (FGFs), transforming growth factor beta-1 (TGF-b), insulin-like growth factor-I (IGF-I) and platelet-derived growth factor (PDGF) which can facilitate repair and regeneration. Moreover, a clinical trial of PRP in severe angina patients has shown its excellent safety profile. However, PRP is a very complex biological substance with an array of active biomolecules, its functions are yet to be fully clarified. In-addition, there was insufficient work assessing possible cardiovascular tissue benefits from PRP. Thus, it still remains necessary to identify the most clinically important cardiovascular applications and further research in clinical scenario need to be validated.
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Key Words
- ADMSC, adipose-derived mesenchymal stem cells
- BMSCs, bone marrow-derived mesenchymal stem cells
- Cardiac injury
- Cell repair and regeneration
- EGF, epidermal growth factor
- FDPs, fibrin degradation products
- FGFs, fibroblast growth factors
- HGF, hepatocyte growth factor
- IGF-I, insulin-like growth factor-I
- IRI, ischemic reperfusion injury
- ISO, Isoproterenol
- LP-PRP, leukocyte-poor PRP
- LR-PRP, leukocyte-rich PRP
- MH, Manuka honey
- MI, myocardial infarction
- MRI, magnetic resonance imaging
- P-PRF, pure platelet-rich fibrin
- PDGF, platelet-derived growth factor
- PRP, platelet-rich plasma
- Platelet-rich plasma
- ROS, reactive oxygen species
- TGF-b, transforming growth factor beta
- VEGF, vascular endothelial growth factor
- nsPEF, nanosecond pulsed electric fields
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Affiliation(s)
- Syed Sarim Imam
- Department of Pharmaceutics, College of Pharmacy, King Saud University, Riyadh, Saudi Arabia
| | - Fahad A. Al-Abbasi
- Department of Biochemistry, Faculty of Science, King Abdulaziz University Jeddah 21589 Saudi Arabia
| | - Salman Hosawi
- Department of Biochemistry, Faculty of Science, King Abdulaziz University Jeddah 21589 Saudi Arabia
| | - Muhammad Afzal
- Department of Pharmacology, College of Pharmacy, Jouf University, Sakaka, Aljouf-72341, Saudi Arabia
| | - Muhammad Shahid Nadeem
- Department of Biochemistry, Faculty of Science, King Abdulaziz University Jeddah 21589 Saudi Arabia
| | - Mohammed M. Ghoneim
- Department of Pharmacy Practice, College of Pharmacy, AlMaarefa University, Ad Diriyah 13713, Saudi Arabia
| | - Sultan Alshehri
- Department of Pharmaceutics, College of Pharmacy, King Saud University, Riyadh, Saudi Arabia
| | - Sami I. Alzarea
- Department of Pharmacology, College of Pharmacy, Jouf University, Sakaka, Aljouf-72341, Saudi Arabia
| | - Ali Alquraini
- Department of Pharmaceutical Chemistry, Faculty of Clinical Pharmacy, Al Baha University, Al Baha 65779, Saudi Arabia
| | - Gaurav Gupta
- Department of Pharmacology, School of Pharmacy, Suresh Gyan Vihar University, Jagatpura, Jaipur, India
- Department of Pharmacology, Saveetha Dental College, Saveetha Institute of Medical and Technical Sciences, Saveetha University, Chennai, India
| | - Imran Kazmi
- Department of Biochemistry, Faculty of Science, King Abdulaziz University Jeddah 21589 Saudi Arabia
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Sassoli C, Garella R, Chellini F, Tani A, Pavan P, Bambi F, Zecchi-Orlandini S, Squecco R. Platelet-rich plasma affects gap junctional features in myofibroblasts in vitro via vascular endothelial growth factor (VEGF)-A/VEGF receptor. Exp Physiol 2021; 107:106-121. [PMID: 34935228 DOI: 10.1113/ep090052] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/11/2021] [Accepted: 12/14/2021] [Indexed: 12/14/2022]
Abstract
NEW FINDINGS What is the central question of this study? It is a challenge to discover effective therapies for fibrosis. Increasing evidence supports the antifibrotic potential of platelet-rich plasma (PRP) as a source of bioactive molecules, such as vascular endothelial growth factor (VEGF)-A. However, the effects and mechanisms of action of PRP need to be clarified. What is the main finding and its importance? This report clarifies the mechanisms mediating the antifibrotic action of PRP, strengthening the role of VEGF-A/VEGF receptor, and identifies gap junction currents and connexin 43 as novel targets of this pathway in the fibroblast-to-myofibroblast transition induced by the transforming growth factor-β1. ABSTRACT Despite increasing experimental evidence, the antifibrotic potential of platelet-rich plasma (PRP) remains controversial, and its mechanisms of action are not fully clarified. This short report extends our previous research on the capability of PRP to prevent the in vitro differentiation of fibroblasts toward myofibroblasts, the key effectors of fibrosis, induced by the profibrotic agent transforming growth factor-β1 (TGF-β1). In particular, we focused on the involvement of signalling mediated by vascular endothelial growth factor (VEGF)-A/VEGF receptor (VEGFR) in the PRP-induced fibroblast response, highlighting gap junction features. Electrophysiological and morphological analyses revealed that PRP hindered morphofunctional differentiation of both murine NIH/3T3 and human primary adult skin fibroblasts toward myofibroblasts as judged by the analysis of membrane phenomena, α-smooth muscle actin and vinculin expression and cell morphology. Neutralization of VEGF-A by blocking antibodies or pharmacological inhibition of VEGFR by KRN633 in TGF-β1-treated fibroblasts prevented the PRP-promoted effects, such as the reduction of voltage-dependent transjunctional currents in cell pairs and a decreased expression of connexin 43, the typical connexin isoform forming voltage-dependent connexons. The role of VEGF-A in inhibiting these events was confirmed by treating TGF-β1-stimulated fibroblasts with soluble VEGF-A. The results obtained when cells were differentiated using KRN633 alone suggest an antagonistic cross-talk between TGF-β1 and VEGFR. In conclusion, this study identifies, for the first time, gap junction currents as crucial targets in the VEGF-A/VEGFR-mediated antifibrotic pathway and provides new insights into mechanisms behind the action of PRP in preventing differentiation of fibroblasts to myofibroblasts.
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Affiliation(s)
- Chiara Sassoli
- Section of Anatomy and Histology, Department of Experimental and Clinical Medicine, University of Florence, Florence, Italy
| | - Rachele Garella
- Section of Physiological Sciences, Department of Experimental and Clinical Medicine, University of Florence, Florence, Italy
| | - Flaminia Chellini
- Section of Anatomy and Histology, Department of Experimental and Clinical Medicine, University of Florence, Florence, Italy
| | - Alessia Tani
- Section of Anatomy and Histology, Department of Experimental and Clinical Medicine, University of Florence, Florence, Italy
| | - Paola Pavan
- Transfusion Medicine and Cell Therapy Unit, 'A. Meyer' University Children's Hospital, Florence, Italy
| | - Franco Bambi
- Transfusion Medicine and Cell Therapy Unit, 'A. Meyer' University Children's Hospital, Florence, Italy
| | - Sandra Zecchi-Orlandini
- Section of Anatomy and Histology, Department of Experimental and Clinical Medicine, University of Florence, Florence, Italy
| | - Roberta Squecco
- Section of Physiological Sciences, Department of Experimental and Clinical Medicine, University of Florence, Florence, Italy
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Qian B, Yang Q, Wang M, Huang S, Jiang C, Shi H, Long Q, Zhou M, Zhao Q, Ye X. Encapsulation of lyophilized platelet-rich fibrin in alginate-hyaluronic acid hydrogel as a novel vascularized substitution for myocardial infarction. Bioact Mater 2021; 7:401-411. [PMID: 34466741 PMCID: PMC8379365 DOI: 10.1016/j.bioactmat.2021.05.042] [Citation(s) in RCA: 32] [Impact Index Per Article: 8.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/04/2021] [Revised: 05/19/2021] [Accepted: 05/24/2021] [Indexed: 12/23/2022] Open
Abstract
Cardiovascular diseases such as myocardial infarction (MI) are among the major causes of death worldwide. Although intramyocardial injection of hydrogels can effectively enhance the ventricular wall, this approach is limited because of its restriction to the poor vascularization in the infarcted myocardium. Here, we reported a new type of hydrogel composed of alginate (ALG) and hyaluronic acid (HA) with lyophilized platelet-rich fibrin (Ly-PRF) for releasing abundant growth factors to realize their respective functions. The results of in vitro studies demonstrated favorable mechanical property and release ability of ALG-HA with Ly-PRF. When injected into the infarcted myocardium, this composite hydrogel preserved heart function and the Ly-PRF within the hydrogel promoted angiogenesis and increased vascular density in both infarcted and border zone, which rescued the ischemic myocardium. These beneficial effects were also accompanied by macrophage polarization and regulation of myocardial fibrosis. Moreover, the autologous origin of Ly-PRF with ALG-HA hydrogel offers myriad advantages including safety profile, easiness to obtain and cost-effectiveness. Overall, this study demonstrated the versatile therapeutic effects of a novel composite hydrogel ALG-HA with Ly-PRF, which optimizes a promising vascularized substitution strategy for improving cardiac function after MI.
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Key Words
- ALG, alginate
- BZ, border zone
- Drug delivery
- HA, hyaluronic acid
- IZ, infarcted zone
- Injectable hydrogel
- LVEDd, left ventricular end-diastolic diameter
- LVEF, left ventricular ejection fractions
- LVESd, left ventricular end-systolic diameter
- LVFS, left ventricular fractional shortening
- Ly-PRF, lyophilized platelet-rich fibrin
- Lyophilized platelet-rich fibrin
- MI, myocardial infarction
- Myocardial infarction
- PET-CT, positron emission tomography-computerized tomography
- PRF, platelet-rich fibrin
- PRP, platelet rich plasma
- SUV, standardized uptake value
- TUNEL, terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick-end labeling
- Vascularization
- iNOS, inducible nitric oxide synthase
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Affiliation(s)
- Bei Qian
- Department of Cardiovascular Surgery, Ruijin Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, 200025, China
| | - Qi Yang
- Department of Cardiovascular Surgery, Ruijin Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, 200025, China
| | - Mingliang Wang
- Department of Cardiology, Putuo People's Hospital, Tongji University, Shanghai, 200060, China
| | - Shixing Huang
- Department of Cardiovascular Surgery, Ruijin Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, 200025, China
| | - Chenyu Jiang
- Department of Cardiovascular Surgery, Ruijin Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, 200025, China
| | - Hongpeng Shi
- Department of Cardiovascular Surgery, Ruijin Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, 200025, China
| | - Qiang Long
- Department of Cardiovascular Surgery, Ruijin Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, 200025, China
| | - Mi Zhou
- Department of Cardiovascular Surgery, Ruijin Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, 200025, China
| | - Qiang Zhao
- Department of Cardiovascular Surgery, Ruijin Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, 200025, China
| | - Xiaofeng Ye
- Department of Cardiovascular Surgery, Ruijin Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, 200025, China
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Wang D, Li T, Xu Y, Yang X, He M, Zhang Z, Wu W, Yan Y. [Platelet-rich plasma alleviates myocardial ischemia-reperfusion injury in rats]. NAN FANG YI KE DA XUE XUE BAO = JOURNAL OF SOUTHERN MEDICAL UNIVERSITY 2021; 41:775-782. [PMID: 34134967 DOI: 10.12122/j.issn.1673-4254.2021.05.20] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Subscribe] [Scholar Register] [Indexed: 11/24/2022]
Abstract
OBJECTIVE To investigate the protective effect of platelet-rich plasma (PRP) against acute myocardial ischemiareperfusion (IR) injury and the possible mechanism. OBJECTIVE Aortic blood samples were collected from 10 SD rats to prepare PRP, in which the concentrations of platelet-derived growth factor-BB (PDGF-BB) and transforming growth factor-β1 (TGF-β1) were measured. Cell models of IR injury were established in primary cultures of neonatal SD rat cardiomyocytes by exposing the cells to 3 h of hypoxia. The cells were then reoxygenated and co-cultured with 1%, 5%, 10%, and 20% volume of PRP for 12 h, and the changes in cell viability was assessed. Immunofluorescence staining of the cardiomyocytes was performed, and the cellular expression of AMPK and its phosphorylation level were detected. The effects of PRP on the proliferation and migration of rat aortic endothelial cells (RAOECs) were examined. In a SD rat model of myocardial IR injury, 100 μL of PRP (n= 20) or normal saline (n=20) was injected at 4 sites around the ligation site immediately after cardiac reperfusion. One day after the injection, 6 rats were selected from each group for TTC staining of the myocardial tissues and measurement of troponin Ⅰ content. One week later, the cardiac function of the remaining rats was assessed by echocardiography, and HE staining of the myocardial tissues was performed. The effect of PRP treatment for 24 h on polarization of M1 and M2 macrophages was also examined by flow cytometry in RAW264.7 cells after hypoxic exposure for 3 h. OBJECTIVE The concentrations of PDGF-BB and TGF-β1 were significantly higher in PRP than in whole blood. Addition of 1% volume of PRP significantly reduced death of the cardiomyocytes following reoxygenation, and this effect was closely related with the activation of AMPK. Treatment with PRP obviously promoted the proliferation and migration of RAOECs. In rat models of acute myocardial IR injury, injections of PRP significantly reduced the infarct size and troponin Ⅰ concentration as compared with saline injection (P < 0.001). One week after PRP injection, the rats showed significantly improved cardiac function with a lowered level of inflammatory response in comparison with the rats with saline injection. In RAW264.7 cells with hypoxic exposure, treatment with PRP obviously decreased the number of M1 macrophages and increase the number of M2 macrophages. OBJECTIVE PRP can improve acute myocardial IR injury in rats by phosphorylating AMPK and regulating macrophage polarization, which produces a protective immunomodulatory effect on the ischemic myocardial tissues.
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Affiliation(s)
- D Wang
- Department of Cardiology, Third Affiliated Hospital of Guangzhou Medical University, Guangzhou 510150, China.,Translational Research Centre of Regenerative Medicine and 3D Printing, Guangzhou Medical University, Guangzhou 510150, China.,State Key Laboratory of Organ Failure Research, Department of Pathophysiology, Guangzhou 510515, China
| | - T Li
- Department of Cardiology, Third Affiliated Hospital of Guangzhou Medical University, Guangzhou 510150, China.,State Key Laboratory of Organ Failure Research, Department of Pathophysiology, Guangzhou 510515, China.,Guangdong Provincial Key Laboratory for Shock and Microcirculation Research, Southern Medical University, Guangzhou 510515, China
| | - Y Xu
- Department of Cardiology, Third Affiliated Hospital of Guangzhou Medical University, Guangzhou 510150, China.,Guangdong Provincial Key Laboratory for Shock and Microcirculation Research, Southern Medical University, Guangzhou 510515, China
| | - X Yang
- Department of Cardiology, Third Affiliated Hospital of Guangzhou Medical University, Guangzhou 510150, China.,Guangdong Provincial Key Laboratory for Shock and Microcirculation Research, Southern Medical University, Guangzhou 510515, China
| | - M He
- State Key Laboratory of Organ Failure Research, Department of Pathophysiology, Guangzhou 510515, China
| | - Z Zhang
- Translational Research Centre of Regenerative Medicine and 3D Printing, Guangzhou Medical University, Guangzhou 510150, China
| | - W Wu
- Guangdong Provincial Key Laboratory for Shock and Microcirculation Research, Southern Medical University, Guangzhou 510515, China
| | - Y Yan
- Department of Cardiology, Third Affiliated Hospital of Guangzhou Medical University, Guangzhou 510150, China.,Translational Research Centre of Regenerative Medicine and 3D Printing, Guangzhou Medical University, Guangzhou 510150, China.,State Key Laboratory of Organ Failure Research, Department of Pathophysiology, Guangzhou 510515, China
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10
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Sazzad F, Kuzemczak M, Loh E, Wu W, Kofidis T. Targeted Myocardial Restoration with Injectable Hydrogels-In Search of The Holy Grail in Regenerating Damaged Heart Tissue. Biomedicines 2021; 9:biomedicines9060595. [PMID: 34073912 PMCID: PMC8225139 DOI: 10.3390/biomedicines9060595] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/21/2021] [Revised: 05/17/2021] [Accepted: 05/18/2021] [Indexed: 12/20/2022] Open
Abstract
A 3-dimensional, robust, and sustained myocardial restoration by means of tissue engineering remains an experimental approach. Prolific protocols have been developed and tested in small and large animals, but, as clinical cardiac surgeons, we have not arrived at the privilege of utilizing any of them in our clinical practice. The question arises as to why this is. The heart is a unique organ, anatomically and functionally. It is not an easy target to replicate with current techniques, or even to support in its viability and function. Currently, available therapies fail to reverse the loss of functional cardiac tissue, the fundamental pathology remains unaddressed, and heart transplantation is an ultima ratio treatment option. Owing to the equivocal results of cell-based therapies, several strategies have been pursued to overcome the limitations of the current treatment options. Preclinical data, as well as first-in-human studies, conducted to-date have provided important insights into the understanding of injection-based approaches for myocardial restoration. In light of the available data, injectable biomaterials suitable for transcatheter delivery appear to have the highest translational potential. This article presents a current state-of-the-literature review in the field of hydrogel-based myocardial restoration therapy.
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Affiliation(s)
- Faizus Sazzad
- Myocardial Experimental Laboratory, Department of Surgery, Yong Loo Lin School of Medicine, National University of Singapore, Singapore 117599, Singapore; (F.S.); (E.L.); (W.W.)
| | - Michał Kuzemczak
- Department of Invasive Cardiology, Central Clinical Hospital of the Ministry of Interior and Administration, 02-507 Warsaw, Poland;
- Department of Medical Rescue, Poznan University of Medical Sciences, 60-806 Poznań, Poland
| | - Engracia Loh
- Myocardial Experimental Laboratory, Department of Surgery, Yong Loo Lin School of Medicine, National University of Singapore, Singapore 117599, Singapore; (F.S.); (E.L.); (W.W.)
| | - Wellington Wu
- Myocardial Experimental Laboratory, Department of Surgery, Yong Loo Lin School of Medicine, National University of Singapore, Singapore 117599, Singapore; (F.S.); (E.L.); (W.W.)
| | - Theo Kofidis
- Myocardial Experimental Laboratory, Department of Surgery, Yong Loo Lin School of Medicine, National University of Singapore, Singapore 117599, Singapore; (F.S.); (E.L.); (W.W.)
- Department of Cardiac, Thoracic and Vascular Surgery, National University Health System, Singapore 119228, Singapore
- Correspondence: ; Tel.: +65-6772-6505
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11
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Yeo J, Lee J, Lee S, Kim WJ. Polymeric Antioxidant Materials for Treatment of Inflammatory Disorders. ADVANCED THERAPEUTICS 2021. [DOI: 10.1002/adtp.202000270] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/14/2022]
Affiliation(s)
- Jiwon Yeo
- Department of Chemistry Pohang University of Science and Technology (POSTECH) Pohang 37673 Republic of Korea
| | - Junseok Lee
- Department of Chemistry Pohang University of Science and Technology (POSTECH) Pohang 37673 Republic of Korea
- OmniaMed Co, Ltd Pohang 37673 Republic of Korea
| | - Sanggi Lee
- School of Interdisciplinary Bioscience and Bioengineering (I‐Bio) Pohang University of Science and Technology (POSTECH) Pohang 37673 Republic of Korea
| | - Won Jong Kim
- Department of Chemistry Pohang University of Science and Technology (POSTECH) Pohang 37673 Republic of Korea
- OmniaMed Co, Ltd Pohang 37673 Republic of Korea
- School of Interdisciplinary Bioscience and Bioengineering (I‐Bio) Pohang University of Science and Technology (POSTECH) Pohang 37673 Republic of Korea
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12
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Charles CJ, Li RR, Yeung T, Mazlan SMI, Lai RC, de Kleijn DPV, Lim SK, Richards AM. Systemic Mesenchymal Stem Cell-Derived Exosomes Reduce Myocardial Infarct Size: Characterization With MRI in a Porcine Model. Front Cardiovasc Med 2020; 7:601990. [PMID: 33304934 PMCID: PMC7701257 DOI: 10.3389/fcvm.2020.601990] [Citation(s) in RCA: 38] [Impact Index Per Article: 7.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/02/2020] [Accepted: 10/16/2020] [Indexed: 12/26/2022] Open
Abstract
The observations that mesenchymal stem cells (MSCs) exert cardiac protection and repair via their secretome with the active component(s) identified as exosomes underpinned our test of the efficacy of MSC exosomes in a porcine model of myocardial infarction (MI) when administered systemically by the convenient method of intravenous (IV) bolus injection. Results show that 7 days of IV exosomes results in clear reduction (30-40%) of infarct size measured at both 7 and 28 days post-MI, despite near identical release of hs Troponin T. Together with reduced infarct size, exosome treatment reduced transmurality and lessened wall thinning in the infarct zone. Exosome treated pigs showed relative preservation of LV function with significant amelioration of falls in fractional wall thickening compared with control. However, global measures of LV function were less protected by exosome treatment. It is possible that greater preservation of global LV function may have been attenuated by increased cardiac fibrosis, as T1 values showed significant increase in the exosome pigs compared to control particularly in the infarct related segments. Taken together, these results show clear effects of IV exosomes administered over 7 days to reduce infarct size with relatively preserved cardiac function compared to control treated infarct pigs.
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Affiliation(s)
- Christopher J. Charles
- Cardiovascular Research Institute (CVRI), National University Heart Centre, Singapore, Singapore
- Department of Surgery, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore
- Department of Medicine, Christchurch Heart Institute, University of Otago, Christchurch, New Zealand
| | - Renee R. Li
- Cardiovascular Research Institute (CVRI), National University Heart Centre, Singapore, Singapore
- Department of Surgery, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore
| | - Teresa Yeung
- Cardiovascular Research Institute (CVRI), National University Heart Centre, Singapore, Singapore
- Department of Surgery, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore
| | - Stephane M. Ibraham Mazlan
- Cardiovascular Research Institute (CVRI), National University Heart Centre, Singapore, Singapore
- Department of Surgery, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore
| | - Ruenn Chai Lai
- Institute of Medical Biology, Agency for Science, Technology and Research (ASTAR), Singapore, Singapore
| | - Dominique P. V. de Kleijn
- Department of Vascular Surgery, University Medical Centre, Utrecht, and Netherlands Heart Institute, Utrecht, Netherlands
| | - Sai Kiang Lim
- Department of Surgery, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore
- Institute of Medical Biology, Agency for Science, Technology and Research (ASTAR), Singapore, Singapore
| | - A. Mark Richards
- Cardiovascular Research Institute (CVRI), National University Heart Centre, Singapore, Singapore
- Department of Medicine, Christchurch Heart Institute, University of Otago, Christchurch, New Zealand
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13
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Squecco R, Chellini F, Idrizaj E, Tani A, Garella R, Pancani S, Pavan P, Bambi F, Zecchi-Orlandini S, Sassoli C. Platelet-Rich Plasma Modulates Gap Junction Functionality and Connexin 43 and 26 Expression During TGF-β1-Induced Fibroblast to Myofibroblast Transition: Clues for Counteracting Fibrosis. Cells 2020; 9:cells9051199. [PMID: 32408529 PMCID: PMC7290305 DOI: 10.3390/cells9051199] [Citation(s) in RCA: 20] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/07/2020] [Revised: 04/28/2020] [Accepted: 05/08/2020] [Indexed: 12/19/2022] Open
Abstract
Skeletal muscle repair/regeneration may benefit by Platelet-Rich Plasma (PRP) treatment owing to PRP pro-myogenic and anti-fibrotic effects. However, PRP anti-fibrotic action remains controversial. Here, we extended our previous researches on the inhibitory effects of PRP on in vitro transforming growth factor (TGF)-β1-induced differentiation of fibroblasts into myofibroblasts, the effector cells of fibrosis, focusing on gap junction (GJ) intercellular communication. The myofibroblastic phenotype was evaluated by cell shape analysis, confocal fluorescence microscopy and Western blotting analyses of α-smooth muscle actin and type-1 collagen expression, and electrophysiological recordings of resting membrane potential, resistance, and capacitance. PRP negatively regulated myofibroblast differentiation by modifying all the assessed parameters. Notably, myofibroblast pairs showed an increase of voltage-dependent GJ functionality paralleled by connexin (Cx) 43 expression increase. TGF-β1-treated cells, when exposed to a GJ blocker, or silenced for Cx43 expression, failed to differentiate towards myofibroblasts. Although a minority, myofibroblast pairs also showed not-voltage-dependent GJ currents and coherently Cx26 expression. PRP abolished the TGF-β1-induced voltage-dependent GJ current appearance while preventing Cx43 increase and promoting Cx26 expression. This study adds insights into molecular and functional mechanisms regulating fibroblast-myofibroblast transition and supports the anti-fibrotic potential of PRP, demonstrating the ability of this product to hamper myofibroblast generation targeting GJs.
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Affiliation(s)
- Roberta Squecco
- Department of Experimental and Clinical Medicine, Section of Physiological Sciences, University of Florence, 50134 Florence, Italy; (R.S.); (E.I.); (R.G.)
| | - Flaminia Chellini
- Department of Experimental and Clinical Medicine, Section of Anatomy and Histology, University of Florence, 50134 Florence, Italy; (F.C.); (A.T.); (S.P.); (S.Z.-O.)
| | - Eglantina Idrizaj
- Department of Experimental and Clinical Medicine, Section of Physiological Sciences, University of Florence, 50134 Florence, Italy; (R.S.); (E.I.); (R.G.)
| | - Alessia Tani
- Department of Experimental and Clinical Medicine, Section of Anatomy and Histology, University of Florence, 50134 Florence, Italy; (F.C.); (A.T.); (S.P.); (S.Z.-O.)
| | - Rachele Garella
- Department of Experimental and Clinical Medicine, Section of Physiological Sciences, University of Florence, 50134 Florence, Italy; (R.S.); (E.I.); (R.G.)
| | - Sofia Pancani
- Department of Experimental and Clinical Medicine, Section of Anatomy and Histology, University of Florence, 50134 Florence, Italy; (F.C.); (A.T.); (S.P.); (S.Z.-O.)
| | - Paola Pavan
- Transfusion Medicine and Cell Therapy Unit, "A. Meyer" University Children’s Hospital, 50134 Florence, Italy; (P.P.); (F.B.)
| | - Franco Bambi
- Transfusion Medicine and Cell Therapy Unit, "A. Meyer" University Children’s Hospital, 50134 Florence, Italy; (P.P.); (F.B.)
| | - Sandra Zecchi-Orlandini
- Department of Experimental and Clinical Medicine, Section of Anatomy and Histology, University of Florence, 50134 Florence, Italy; (F.C.); (A.T.); (S.P.); (S.Z.-O.)
| | - Chiara Sassoli
- Department of Experimental and Clinical Medicine, Section of Anatomy and Histology, University of Florence, 50134 Florence, Italy; (F.C.); (A.T.); (S.P.); (S.Z.-O.)
- Correspondence: ; Tel.: +39-0552-7580-63
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14
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Analyzing Impetus of Regenerative Cellular Therapeutics in Myocardial Infarction. J Clin Med 2020; 9:jcm9051277. [PMID: 32354170 PMCID: PMC7287592 DOI: 10.3390/jcm9051277] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/14/2020] [Revised: 04/20/2020] [Accepted: 04/26/2020] [Indexed: 02/06/2023] Open
Abstract
Both vasculature and myocardium in the heart are excessively damaged following myocardial infarction (MI), hence therapeutic strategies for treating MI hearts should concurrently aim for true cardiac repair by introducing new cardiomyocytes to replace lost or injured ones. Of them, mesenchymal stem cells (MSCs) have long been considered a promising candidate for cell-based therapy due to their unspecialized, proliferative differentiation potential to specific cell lineage and, most importantly, their capacity of secreting beneficial paracrine factors which further promote neovascularization, angiogenesis, and cell survival. As a consequence, the differentiated MSCs could multiply and replace the damaged tissues to and turn into tissue- or organ-specific cells with specialized functions. These cells are also known to release potent anti-fibrotic factors including matrix metalloproteinases, which inhibit the proliferation of cardiac fibroblasts, thereby attenuating fibrosis. To achieve the highest possible therapeutic efficacy of stem cells, the other interventions, including hydrogels, electrical stimulations, or platelet-derived biomaterials, have been supplemented, which have resulted in a narrow to broad range of outcomes. Therefore, this article comprehensively analyzed the progress made in stem cells and combinatorial therapies to rescue infarcted myocardium.
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15
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Ke X, Li M, Wang X, Liang J, Wang X, Wu S, Long M, Hu C. An injectable chitosan/dextran/β -glycerophosphate hydrogel as cell delivery carrier for therapy of myocardial infarction. Carbohydr Polym 2020; 229:115516. [DOI: 10.1016/j.carbpol.2019.115516] [Citation(s) in RCA: 68] [Impact Index Per Article: 13.6] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/04/2019] [Revised: 10/18/2019] [Accepted: 10/21/2019] [Indexed: 12/13/2022]
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16
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Chellini F, Tani A, Vallone L, Nosi D, Pavan P, Bambi F, Zecchi-Orlandini S, Sassoli C. Platelet-Rich Plasma and Bone Marrow-Derived Mesenchymal Stromal Cells Prevent TGF-β1-Induced Myofibroblast Generation but Are Not Synergistic when Combined: Morphological in vitro Analysis. Cells Tissues Organs 2019; 206:283-295. [PMID: 31382258 DOI: 10.1159/000501499] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/02/2019] [Accepted: 06/14/2019] [Indexed: 11/19/2022] Open
Abstract
The persistence of activated myofibroblasts is a hallmark of fibrosis of many organs. Thus, the modulation of the generation/functionality of these cells may represent a strategical anti-fibrotic therapeutic option. Bone marrow-derived mesenchymal stromal cell (MSC)-based therapy has shown promising clues, but some criticisms still limit the clinical use of these cells, including the need to avoid xenogeneic compound contamination for ex vivo cell amplification and the identification of appropriate growth factors acting as a pre-conditioning agent and/or cell delivery vehicle during transplantation, thus enabling the improvement of cell survival in the host tissue microenvironment. Many studies have demonstrated the ability of platelet-rich plasma (PRP), a source of many biologically active molecules, to positively influence MSC proliferation, survival, and functionality, as well as its anti-fibrotic potential. Here we investigated the effects of PRP, murine and human bone marrow-derived MSCs, and of the combined treatment PRP/MSCs on in vitro differentiation of murine NIH/3T3 and human HDFα fibroblasts to myofibroblasts induced by transforming growth factor (TGF)-β1, a well-known pro-fibrotic agent. The myofibroblastic phenotype was evaluated morphologically (cell shape and actin cytoskeleton assembly) and immunocytochemically (vinculin-rich focal adhesion clustering, α-smooth muscle actin and type-1 collagen expression). We found that PRP and MSCs, both as single treatments and in combination, were able to prevent the TGF-β1-induced fibroblast-myofibroblast transition. Unexpectedly, the combination PRP/MSCs had no synergistic effects. In conclusion, within the limitations related to an in vitro experimentation, our study may contribute to providing an experimental background for supporting the anti-fibrotic potential of the combination PRP/MSCs which, once translated "from bench to bedside," could potentially offer advantages over the single treatments.
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Affiliation(s)
- Flaminia Chellini
- Department of Experimental and Clinical Medicine, Section of Anatomy and Histology, University of Florence, Florence, Italy
| | - Alessia Tani
- Department of Experimental and Clinical Medicine, Section of Anatomy and Histology, University of Florence, Florence, Italy
| | - Larissa Vallone
- Department of Experimental and Clinical Medicine, Section of Anatomy and Histology, University of Florence, Florence, Italy
| | - Daniele Nosi
- Department of Experimental and Clinical Medicine, Section of Anatomy and Histology, University of Florence, Florence, Italy
| | - Paola Pavan
- Transfusion Medicine and Cell Therapy Unit, "A. Meyer" University Children's Hospital, Florence, Italy
| | - Franco Bambi
- Transfusion Medicine and Cell Therapy Unit, "A. Meyer" University Children's Hospital, Florence, Italy
| | - Sandra Zecchi-Orlandini
- Department of Experimental and Clinical Medicine, Section of Anatomy and Histology, University of Florence, Florence, Italy
| | - Chiara Sassoli
- Department of Experimental and Clinical Medicine, Section of Anatomy and Histology, University of Florence, Florence, Italy,
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17
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Kuraitis D, Hosoyama K, Blackburn NJR, Deng C, Zhong Z, Suuronen EJ. Functionalization of soft materials for cardiac repair and regeneration. Crit Rev Biotechnol 2019; 39:451-468. [PMID: 30929528 DOI: 10.1080/07388551.2019.1572587] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/22/2022]
Abstract
Coronary artery disease is a leading cause of death in developed nations. As the disease progresses, myocardial infarction can occur leaving areas of dead tissue in the heart. To compensate, the body initiates its own repair/regenerative response in an attempt to restore function to the heart. These efforts serve as inspiration to researchers who attempt to capitalize on the natural regenerative processes to further augment repair. Thus far, researchers are exploiting these repair mechanisms in the functionalization of soft materials using a variety of growth factor-, ligand- and peptide-incorporating approaches. The goal of functionalizing soft materials is to best promote and direct the regenerative responses that are needed to restore the heart. This review summarizes the opportunities for the use of functionalized soft materials for cardiac repair and regeneration, and some of the different strategies being developed.
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Affiliation(s)
- Drew Kuraitis
- a Division of Cardiac Surgery , University of Ottawa Heart Institute , Ottawa , Canada
| | - Katsuhiro Hosoyama
- a Division of Cardiac Surgery , University of Ottawa Heart Institute , Ottawa , Canada
| | - Nick J R Blackburn
- a Division of Cardiac Surgery , University of Ottawa Heart Institute , Ottawa , Canada
| | - Chao Deng
- b Biomedical Polymers Laboratory, and Jiangsu Key Laboratory of Advanced Functional Polymer Design and Application, College of Chemistry, Chemical Engineering and Materials Science , Soochow University , Suzhou , People's Republic of China
| | - Zhiyuan Zhong
- b Biomedical Polymers Laboratory, and Jiangsu Key Laboratory of Advanced Functional Polymer Design and Application, College of Chemistry, Chemical Engineering and Materials Science , Soochow University , Suzhou , People's Republic of China
| | - Erik J Suuronen
- a Division of Cardiac Surgery , University of Ottawa Heart Institute , Ottawa , Canada
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Lalegül-Ülker Ö, Şeker Ş, Elçin AE, Elçin YM. Encapsulation of bone marrow-MSCs in PRP-derived fibrin microbeads and preliminary evaluation in a volumetric muscle loss injury rat model: modular muscle tissue engineering. ARTIFICIAL CELLS NANOMEDICINE AND BIOTECHNOLOGY 2018; 47:10-21. [PMID: 30514127 DOI: 10.1080/21691401.2018.1540426] [Citation(s) in RCA: 20] [Impact Index Per Article: 2.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 12/31/2022]
Abstract
Repair of volumetric muscle loss (VML) injuries is a complicated endeavour which necessitates the collaborative use of different regenerative approaches and technologies. Herein is proposed the development of fibrin-based microbeads (FMs) alone or as a bone marrow mesenchymal stem cell (MSC) encapsulation matrix for modular muscle engineering. FMs were generated through the ionotropic gelation of alginate and fibrinogen obtained from the platelet-rich plasma of whole blood, and then removing the alginate by citrate treatment. FMs were first characterized by FT-IR, SEM and water uptake tests. Then, the stability of FMs and the mitochondrial dehydrogenase activity of the MSCs encapsulated in FMs were evaluated under in vitro culture conditions. Eventually, the regenerative capacity of the cell-devoid and MSCs-encapsulated FMs was evaluated in a rat VML injury model involving 8 × 4×4 mm3-size bilateral defects in the biceps femoris muscles. The histochemical, immunohistochemical and semi-quantitative histomorphological scoring results retrieved at 30, 60 and 180 days demonstrated that the cell-devoid FMs supported muscle regeneration to a great extent. Moreover, MSCs-encapsulated FMs were more effective in shortening the regeneration period of the injured tissue of the rat VML, resulting in good myofibre orientation, while the Sham group resulted in incomplete repair with fibrotic scar tissue formations.
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Affiliation(s)
- Özge Lalegül-Ülker
- a Tissue Engineering, Biomaterials and Nanobiotechnology Laboratory , Ankara University Faculty of Science, and Ankara University Stem Cell Institute , Ankara , Turkey
| | - Şükran Şeker
- a Tissue Engineering, Biomaterials and Nanobiotechnology Laboratory , Ankara University Faculty of Science, and Ankara University Stem Cell Institute , Ankara , Turkey
| | - Ayşe Eser Elçin
- a Tissue Engineering, Biomaterials and Nanobiotechnology Laboratory , Ankara University Faculty of Science, and Ankara University Stem Cell Institute , Ankara , Turkey
| | - Yaşar Murat Elçin
- a Tissue Engineering, Biomaterials and Nanobiotechnology Laboratory , Ankara University Faculty of Science, and Ankara University Stem Cell Institute , Ankara , Turkey.,b Biovalda Health Technologies, Inc. , Ankara , Turkey
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Eisinger F, Patzelt J, Langer HF. The Platelet Response to Tissue Injury. Front Med (Lausanne) 2018; 5:317. [PMID: 30483508 PMCID: PMC6242949 DOI: 10.3389/fmed.2018.00317] [Citation(s) in RCA: 97] [Impact Index Per Article: 13.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/02/2018] [Accepted: 10/23/2018] [Indexed: 12/16/2022] Open
Abstract
In recent years, various studies have increasingly explained platelet functions not only in their central role as a regulator in cellular hemostasis and coagulation. In fact, there is growing evidence that under specific conditions, platelets act as a mediator between the vascular system, hemostasis, and the immune system. Therefore, they are essential in many processes involved in tissue remodeling and tissue reorganization after injury or inflammatory responses. These processes include the promotion of inflammatory processes, the contribution to innate and adaptive immune responses during bacterial and viral infections, the modulation of angiogenesis, and the regulation of cell apoptosis in steady-state tissue homeostasis or after tissue breakdown. All in all platelets may contribute to the control of tissue homeostasis much more than generally assumed. This review summarizes the current knowledge of platelets as part of the tissue remodeling network and seeks to provide possible translational implications for clinical therapy.
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Affiliation(s)
- Felix Eisinger
- Section for Cardioimmunology, Department of Cardiovascular Medicine, University of Tuebingen, Tübingen, Germany
| | - Johannes Patzelt
- University Clinic for Cardiovascular Medicine, University of Tuebingen, Tübingen, Germany
| | - Harald F. Langer
- Section for Cardioimmunology, Department of Cardiovascular Medicine, University of Tuebingen, Tübingen, Germany
- University Clinic for Cardiovascular Medicine, University of Tuebingen, Tübingen, Germany
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20
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Chellini F, Tani A, Vallone L, Nosi D, Pavan P, Bambi F, Zecchi Orlandini S, Sassoli C. Platelet-Rich Plasma Prevents In Vitro Transforming Growth Factor-β1-Induced Fibroblast to Myofibroblast Transition: Involvement of Vascular Endothelial Growth Factor (VEGF)-A/VEGF Receptor-1-Mediated Signaling †. Cells 2018; 7:cells7090142. [PMID: 30235859 PMCID: PMC6162453 DOI: 10.3390/cells7090142] [Citation(s) in RCA: 36] [Impact Index Per Article: 5.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/31/2018] [Revised: 09/14/2018] [Accepted: 09/16/2018] [Indexed: 02/07/2023] Open
Abstract
The antifibrotic potential of platelet-rich plasma (PRP) is controversial. This study examined the effects of PRP on in vitro transforming growth factor (TGF)-β1-induced differentiation of fibroblasts into myofibroblasts, the main drivers of fibrosis, and the involvement of vascular endothelial growth factor (VEGF)-A in mediating PRP-induced responses. The impact of PRP alone on fibroblast differentiation was also assessed. Myofibroblastic phenotype was evaluated by confocal fluorescence microscopy and western blotting analyses of α-smooth muscle actin (sma) and type-1 collagen expression, vinculin-rich focal adhesion clustering, and stress fiber assembly. Notch-1, connexin 43, and VEGF-A expression were also analyzed by RT-PCR. PRP negatively regulated fibroblast-myofibroblast transition via VEGF-A/VEGF receptor (VEGFR)-1-mediated inhibition of TGF-β1/Smad3 signaling. Indeed TGF-β1/PRP co-treated fibroblasts showed a robust attenuation of the myofibroblastic phenotype concomitant with a decrease of Smad3 expression levels. The VEGFR-1 inhibition by KRN633 or blocking antibodies, or VEGF-A neutralization in these cells prevented the PRP-promoted effects. Moreover PRP abrogated the TGF-β1-induced reduction of VEGF-A and VEGFR-1 cell expression. The role of VEGF-A signaling in counteracting myofibroblast generation was confirmed by cell treatment with soluble VEGF-A. PRP as single treatment did not induce fibroblast myodifferentiation. This study provides new insights into cellular and molecular mechanisms underpinning PRP antifibrotic action.
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Affiliation(s)
- Flaminia Chellini
- Department of Experimental and Clinical Medicine, Section of Anatomy and Histology, University of Florence, 50134 Florence, Italy.
| | - Alessia Tani
- Department of Experimental and Clinical Medicine, Section of Anatomy and Histology, University of Florence, 50134 Florence, Italy.
| | - Larissa Vallone
- Department of Experimental and Clinical Medicine, Section of Anatomy and Histology, University of Florence, 50134 Florence, Italy.
| | - Daniele Nosi
- Department of Experimental and Clinical Medicine, Section of Anatomy and Histology, University of Florence, 50134 Florence, Italy.
| | - Paola Pavan
- Transfusion Medicine and Cell Therapy Unit, "A. Meyer" University Children's Hospital, 50139 Florence, Italy.
| | - Franco Bambi
- Transfusion Medicine and Cell Therapy Unit, "A. Meyer" University Children's Hospital, 50139 Florence, Italy.
| | - Sandra Zecchi Orlandini
- Department of Experimental and Clinical Medicine, Section of Anatomy and Histology, University of Florence, 50134 Florence, Italy.
| | - Chiara Sassoli
- Department of Experimental and Clinical Medicine, Section of Anatomy and Histology, University of Florence, 50134 Florence, Italy.
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21
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Faramarzi N, Yazdi IK, Nabavinia M, Gemma A, Fanelli A, Caizzone A, Ptaszek LM, Sinha I, Khademhosseini A, Ruskin JN, Tamayol A. Patient-Specific Bioinks for 3D Bioprinting of Tissue Engineering Scaffolds. Adv Healthc Mater 2018; 7:e1701347. [PMID: 29663706 PMCID: PMC6422175 DOI: 10.1002/adhm.201701347] [Citation(s) in RCA: 96] [Impact Index Per Article: 13.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/20/2017] [Revised: 01/26/2018] [Indexed: 12/13/2022]
Abstract
Bioprinting has emerged as a promising tool in tissue engineering and regenerative medicine. Various 3D printing strategies have been developed to enable bioprinting of various biopolymers and hydrogels. However, the incorporation of biological factors has not been well explored. As the importance of personalized medicine is becoming more clear, the need for the development of bioinks containing autologous/patient-specific biological factors for tissue engineering applications becomes more evident. Platelet-rich plasma (PRP) is used as a patient-specific source of autologous growth factors that can be easily incorporated to hydrogels and printed into 3D constructs. PRP contains a cocktail of growth factors enhancing angiogenesis, stem cell recruitment, and tissue regeneration. Here, the development of an alginate-based bioink that can be printed and crosslinked upon implantation through exposure to native calcium ions is reported. This platform can be used for the controlled release of PRP-associated growth factors which may ultimately enhance vascularization and stem cell migration.
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Affiliation(s)
- Negar Faramarzi
- Biomaterials Innovation Research Center, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, 02139, USA
- Harvard-MIT Division of Health Sciences and Technology, Massachusetts Institute of Technology, Cambridge, MA, 02139, USA
- Department of Medicine, Massachusetts General Hospital, Harvard Medical School, Boston, MA, 02114, USA
| | - Iman K Yazdi
- Biomaterials Innovation Research Center, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, 02139, USA
- Harvard-MIT Division of Health Sciences and Technology, Massachusetts Institute of Technology, Cambridge, MA, 02139, USA
- Wyss Institute for Biologically Inspired Engineering, Harvard University, Boston, MA, 02115, USA
| | - Mahboubeh Nabavinia
- Biomaterials Innovation Research Center, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, 02139, USA
- Harvard-MIT Division of Health Sciences and Technology, Massachusetts Institute of Technology, Cambridge, MA, 02139, USA
| | - Andrea Gemma
- Biomaterials Innovation Research Center, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, 02139, USA
- Harvard-MIT Division of Health Sciences and Technology, Massachusetts Institute of Technology, Cambridge, MA, 02139, USA
| | - Adele Fanelli
- Biomaterials Innovation Research Center, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, 02139, USA
- Harvard-MIT Division of Health Sciences and Technology, Massachusetts Institute of Technology, Cambridge, MA, 02139, USA
| | - Andrea Caizzone
- Biomaterials Innovation Research Center, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, 02139, USA
- Harvard-MIT Division of Health Sciences and Technology, Massachusetts Institute of Technology, Cambridge, MA, 02139, USA
| | - Leon M Ptaszek
- Department of Medicine, Massachusetts General Hospital, Harvard Medical School, Boston, MA, 02114, USA
| | - Indranil Sinha
- Department of Surgery, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, 02115, USA
| | - Ali Khademhosseini
- Biomaterials Innovation Research Center, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, 02139, USA
- Harvard-MIT Division of Health Sciences and Technology, Massachusetts Institute of Technology, Cambridge, MA, 02139, USA
- Wyss Institute for Biologically Inspired Engineering, Harvard University, Boston, MA, 02115, USA
- Center of Nanotechnology, Department of Physics, King Abdulaziz University, Jeddah, 21569, Saudi Arabia
- Department of Bioengineering, Department of Chemical and Biomolecular Engineering, Department of Radiology, California NanoSystems Institute (CNSI), University of California, Los Angeles, CA, 90095, USA
| | - Jeremy N Ruskin
- Department of Medicine, Massachusetts General Hospital, Harvard Medical School, Boston, MA, 02114, USA
| | - Ali Tamayol
- Biomaterials Innovation Research Center, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, 02139, USA
- Harvard-MIT Division of Health Sciences and Technology, Massachusetts Institute of Technology, Cambridge, MA, 02139, USA
- Wyss Institute for Biologically Inspired Engineering, Harvard University, Boston, MA, 02115, USA
- Department of Mechanical and Materials Engineering, University of Nebraska, Lincoln, Lincoln, NE, 68588, USA
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22
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Jain E, Sheth S, Dunn A, Zustiak SP, Sell SA. Sustained release of multicomponent platelet-rich plasma proteins from hydrolytically degradable PEG hydrogels. J Biomed Mater Res A 2017; 105:3304-3314. [PMID: 28865187 DOI: 10.1002/jbm.a.36187] [Citation(s) in RCA: 32] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/22/2017] [Revised: 07/12/2017] [Accepted: 08/15/2017] [Indexed: 12/14/2022]
Abstract
Platelet-rich plasma (PRP), an autologous blood derived product is a concentrated mix of multiple growth factors and cytokines. Direct injections of PRP are clinically used for treatment of various musculoskeletal disorders and in wound healing. However, PRP therapy has met with limited clinical success possibly due to unpredictable and premature bolus delivery of PRP growth factors. The objective of this study was to predictably control the bioavailability of PRP growth factors using a hydrolytically degradable polyethylene glycol (PEG) hydrogel. We used a step-growth polymerization based on a Michael-type addition reaction between a 6-arm PEG-acrylate and a dithiol crosslinker, which led to the formation of a homogenous hydrogel network under mild, physiologically relevant conditions. Specifically, to model the release of multicomponent PRP through PEG hydrogels, we examined bulk diffusion of PRP as well as model proteins in a size range corresponding to that of growth factors found in PRP. Our results indicated that protein size and hydrogel degradation controlled diffusion of all proteins and that secondary structure of proteins encapsulated during gelation remained unaffected post-release. Analysis of specific PRP proteins released from the hydrogel showed sustained release until complete hydrogel degradation. PRP released from hydrogels promoted proliferation of human dermal fibroblast, indicating retained bioactivity upon encapsulation and release. The versatile hydrogel system holds clinical potential as a therapeutic drug delivery depot of multicomponent mixtures like PRP. © 2017 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 105A: 3304-3314, 2017.
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Affiliation(s)
- Era Jain
- Department of Biomedical Engineering, , Saint Louis University, Saint Louis, Missouri, 63103
| | - Saahil Sheth
- Department of Biomedical Engineering, , Saint Louis University, Saint Louis, Missouri, 63103
| | - Andrew Dunn
- Department of Biomedical Engineering, , Saint Louis University, Saint Louis, Missouri, 63103
| | - Silviya P Zustiak
- Department of Biomedical Engineering, , Saint Louis University, Saint Louis, Missouri, 63103
| | - Scott A Sell
- Department of Biomedical Engineering, , Saint Louis University, Saint Louis, Missouri, 63103
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23
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Zhu Y, Matsumura Y, Wagner WR. Ventricular wall biomaterial injection therapy after myocardial infarction: Advances in material design, mechanistic insight and early clinical experiences. Biomaterials 2017; 129:37-53. [PMID: 28324864 PMCID: PMC5827941 DOI: 10.1016/j.biomaterials.2017.02.032] [Citation(s) in RCA: 56] [Impact Index Per Article: 7.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/06/2016] [Revised: 02/07/2017] [Accepted: 02/26/2017] [Indexed: 12/11/2022]
Abstract
Intramyocardial biomaterial injection therapy for myocardial infarction has made significant progress since concept initiation more than 10 years ago. The interim successes and progress in the first 5 years have been extensively reviewed. During the last 5 years, two phase II clinical trials have reported their long term follow up results and many additional biomaterial candidates have reached preclinical and clinical testing. Also in recent years deeper investigations into the mechanisms behind the beneficial effects associated with biomaterial injection therapy have been pursued, and a variety of process and material parameters have been evaluated for their impact on therapeutic outcomes. This review explores the advances made in this biomaterial-centered approach to ischemic cardiomyopathy and discusses potential future research directions as this therapy seeks to positively impact patients suffering from one of the world's most common sources of mortality.
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Affiliation(s)
- Yang Zhu
- McGowan Institute for Regenerative Medicine, University of Pittsburgh, Pittsburgh, PA, 15219, USA; Department of Bioengineering, University of Pittsburgh, Pittsburgh, PA, 15219, USA
| | - Yasumoto Matsumura
- McGowan Institute for Regenerative Medicine, University of Pittsburgh, Pittsburgh, PA, 15219, USA
| | - William R Wagner
- McGowan Institute for Regenerative Medicine, University of Pittsburgh, Pittsburgh, PA, 15219, USA; Department of Bioengineering, University of Pittsburgh, Pittsburgh, PA, 15219, USA; Department of Surgery, University of Pittsburgh, Pittsburgh, PA, 15219, USA; Department of Chemical Engineering, University of Pittsburgh, Pittsburgh, PA, 15219, USA.
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24
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Long DW, Johnson NR, Jeffries EM, Hara H, Wang Y. Controlled delivery of platelet-derived proteins enhances porcine wound healing. J Control Release 2017; 253:73-81. [PMID: 28315407 PMCID: PMC5482498 DOI: 10.1016/j.jconrel.2017.03.021] [Citation(s) in RCA: 37] [Impact Index Per Article: 4.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/28/2016] [Revised: 03/09/2017] [Accepted: 03/13/2017] [Indexed: 12/22/2022]
Abstract
Platelet-rich plasma (PRP) is widely used for many clinical indications including wound healing due to the high concentrations of growth factors. However, the short half-life of these therapeutic proteins requires multiple large doses, and their efficacy is highly debated among clinicians. Here we report a method of protecting these proteins and releasing them in a controlled manner via a heparin-based coacervate delivery vehicle to improve wound healing in a porcine model. Platelet-derived proteins incorporated into the coacervate were protected and slowly released over 3weeks in vitro. In a porcine model, PRP coacervate significantly accelerated the healing response over 10days, in part by increasing the rate of wound reepithelialization by 35% compared to control. Additionally, PRP coacervate doubled the rate of wound contraction compared to all other treatments, including that of free PRP proteins. Wounds treated with PRP coacervate exhibited increased collagen alignment and an advanced state of vascularity compared to control treatments. These results suggest that this preparation of PRP accelerates healing of cutaneous wounds only as a controlled release formulation. The coacervate delivery vehicle is a simple and effective tool to improve the therapeutic efficacy of platelet-derived proteins for wound healing.
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Affiliation(s)
- Daniel W. Long
- Department of Bioengineering, University of Pittsburgh, Pittsburgh, PA, USA
- McGowan Institute for Regenerative Medicine, University of Pittsburgh, Pittsburgh, PA, USA
| | - Noah R. Johnson
- Department of Bioengineering, University of Pittsburgh, Pittsburgh, PA, USA
- McGowan Institute for Regenerative Medicine, University of Pittsburgh, Pittsburgh, PA, USA
| | - Eric M. Jeffries
- Department of Bioengineering, University of Pittsburgh, Pittsburgh, PA, USA
- McGowan Institute for Regenerative Medicine, University of Pittsburgh, Pittsburgh, PA, USA
| | - Hidetaka Hara
- Thomas E. Starzl Transplantation Institute, University of Pittsburgh, Pittsburgh, PA, USA
- Department of Surgery, University of Pittsburgh, Pittsburgh, PA, USA
| | - Yadong Wang
- Department of Bioengineering, University of Pittsburgh, Pittsburgh, PA, USA
- McGowan Institute for Regenerative Medicine, University of Pittsburgh, Pittsburgh, PA, USA
- Department of Surgery, University of Pittsburgh, Pittsburgh, PA, USA
- Department of Chemical and Petroleum Engineering, University of Pittsburgh, Pittsburgh, PA, USA
- Department of Materials Science and Engineering, University of Pittsburgh, Pittsburgh, PA, USA
- Department of Mechanical Engineering, University of Pittsburgh, Pittsburgh, PA, USA
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25
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Cancedda R, Bollini S, Descalzi F, Mastrogiacomo M, Tasso R. Learning from Mother Nature: Innovative Tools to Boost Endogenous Repair of Critical or Difficult-to-Heal Large Tissue Defects. Front Bioeng Biotechnol 2017; 5:28. [PMID: 28503549 PMCID: PMC5408079 DOI: 10.3389/fbioe.2017.00028] [Citation(s) in RCA: 15] [Impact Index Per Article: 1.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/27/2017] [Accepted: 04/10/2017] [Indexed: 12/16/2022] Open
Abstract
For repair of chronic or difficult-to-heal tissue lesions and defects, major constraints exist to a broad application of cell therapy and tissue engineering approaches, i.e., transplantation of “ex vivo” expanded autologous stem/progenitor cells, alone or associated with carrier biomaterials. To enable a large number of patients to benefit, new strategies should be considered. One of the main goals of contemporary regenerative medicine is to develop new regenerative therapies, inspired from Mother Nature. In all injured tissues, when platelets are activated by tissue contact, their released factors promote innate immune cell migration to the wound site. Platelet-derived factors and factors secreted by migrating immune cells create an inflammatory microenvironment, in turn, causing the activation of angiogenesis and vasculogenesis processes. Eventually, repair or regeneration of the injured tissue occurs via paracrine signals activating, mobilizing or recruiting to the wound site cells with healing potential, such as stem cells, progenitors, or undifferentiated cells derived from the reprogramming of tissue differentiated cells. This review, largely based on our studies, discusses the identification of new tools, inspired by cellular and molecular mechanisms overseeing physiological tissue healing, that could reactivate dormant endogenous regeneration mechanisms lost during evolution and ontogenesis.
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Affiliation(s)
- Ranieri Cancedda
- Biorigen Srl, Genova, Italy.,Department of Experimental Medicine, University of Genova, Genova, Italy
| | - Sveva Bollini
- Department of Experimental Medicine, University of Genova, Genova, Italy
| | | | | | - Roberta Tasso
- IRCCS AOU San Martino-IST National Institute of Cancer Research, Genova, Italy
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26
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Spanò R, Muraglia A, Todeschi MR, Nardini M, Strada P, Cancedda R, Mastrogiacomo M. Platelet-rich plasma-based bioactive membrane as a new advanced wound care tool. J Tissue Eng Regen Med 2017; 12:e82-e96. [PMID: 27863057 DOI: 10.1002/term.2357] [Citation(s) in RCA: 14] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/02/2016] [Revised: 08/24/2016] [Accepted: 11/09/2016] [Indexed: 12/25/2022]
Abstract
Chronic skin ulcers, consequence of diabetes and other pathological conditions, heavily compromise the patient life quality and represent a high and constantly growing cost for National Health Services. Autologous platelet-rich plasma (PRP), has been proposed to treat these lesions. The absence of guidelines for the PRP production and the need of a fresh preparation for each treatment lead us to develop a protocol for the production of an allogenic PRP-based bioactive membrane (BAM), standardized for platelet concentration and growth factor release. This work compares BAMs obtained starting from two different platelet concentrations. There was no direct correlation between the amount of growth factors released by BAM in vitro and the initial platelet count. However, different release kinetics were noticed for different growth factors, suggesting that they were differently retained by the two BAMs. The angiogenic potential of both BAMs was determined by Luminex Angiogenesis Assay. The biological activity of the factors released by the two BAMs was confirmed by cell proliferation and migration. A diabetic mouse chronic ulcer model was used to define the best PRP therapeutic dose in vivo. Both BAMs induced wound healing by increasing the thickness of the regenerated epidermis and the vessel number. However, a too high platelet concentration resulted in a slowdown of the membrane resorption that interfered with the skin healing. Overall, the results indicate that the BAMs could represent a natural and effective wound healing tool for the treatment of skin ulcers. Copyright © 2016 John Wiley & Sons, Ltd.
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Affiliation(s)
- Raffaele Spanò
- Department of Experimental Medicine (DIMES), University of Genova, Genova, Italy.,IRCCS AOU San Martino-IST Istituto Nazionale per la Ricerca sul Cancro, Genova, Italy
| | | | | | - Marta Nardini
- Department of Experimental Medicine (DIMES), University of Genova, Genova, Italy.,IRCCS AOU San Martino-IST Istituto Nazionale per la Ricerca sul Cancro, Genova, Italy
| | - Paolo Strada
- IRCCS AOU San Martino-IST Istituto Nazionale per la Ricerca sul Cancro, Genova, Italy
| | - Ranieri Cancedda
- Department of Experimental Medicine (DIMES), University of Genova, Genova, Italy.,IRCCS AOU San Martino-IST Istituto Nazionale per la Ricerca sul Cancro, Genova, Italy
| | - Maddalena Mastrogiacomo
- Department of Experimental Medicine (DIMES), University of Genova, Genova, Italy.,IRCCS AOU San Martino-IST Istituto Nazionale per la Ricerca sul Cancro, Genova, Italy
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27
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Recovery of oxidative stress-induced damage in Cisd2-deficient cardiomyocytes by sustained release of ferulic acid from injectable hydrogel. Biomaterials 2016; 103:207-218. [DOI: 10.1016/j.biomaterials.2016.06.060] [Citation(s) in RCA: 31] [Impact Index Per Article: 3.4] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/29/2016] [Revised: 06/21/2016] [Accepted: 06/25/2016] [Indexed: 12/11/2022]
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28
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Fan Z, Guan J. Antifibrotic therapies to control cardiac fibrosis. Biomater Res 2016; 20:13. [PMID: 27226899 PMCID: PMC4879750 DOI: 10.1186/s40824-016-0060-8] [Citation(s) in RCA: 97] [Impact Index Per Article: 10.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/22/2016] [Accepted: 05/13/2016] [Indexed: 12/17/2022] Open
Abstract
Cardiac fibrosis occurs naturally after myocardial infarction. While the initially formed fibrotic tissue prevents the infarcted heart tissue from rupture, the progression of cardiac fibrosis continuously expands the size of fibrotic tissue and causes cardiac function decrease. Cardiac fibrosis eventually evolves the infarcted hearts into heart failure. Inhibiting cardiac fibrosis from progressing is critical to prevent heart failure. However, there is no efficient therapeutic approach currently available. Myofibroblasts are primarily responsible for cardiac fibrosis. They are formed by cardiac fibroblast differentiation, fibrocyte differentiation, epithelial to mesenchymal transdifferentiation, and endothelial to mesenchymal transition, driven by cytokines such as transforming growth factor beta (TGF-β), angiotensin II and platelet-derived growth factor (PDGF). The approaches that inhibit myofibroblast formation have been demonstrated to prevent cardiac fibrosis, including systemic delivery of antifibrotic drugs, localized delivery of biomaterials, localized delivery of biomaterials and antifibrotic drugs, and localized delivery of cells using biomaterials. This review addresses current progresses in cardiac fibrosis therapies.
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Affiliation(s)
- Zhaobo Fan
- Department of Materials Science and Engineering, The Ohio State University, 2041 College Road, Columbus, OH 43210 USA
| | - Jianjun Guan
- Department of Materials Science and Engineering, The Ohio State University, 2041 College Road, Columbus, OH 43210 USA
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29
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Garbayo E, Gavira JJ, de Yebenes MG, Pelacho B, Abizanda G, Lana H, Blanco-Prieto MJ, Prosper F. Catheter-based Intramyocardial Injection of FGF1 or NRG1-loaded MPs Improves Cardiac Function in a Preclinical Model of Ischemia-Reperfusion. Sci Rep 2016; 6:25932. [PMID: 27184924 PMCID: PMC4868965 DOI: 10.1038/srep25932] [Citation(s) in RCA: 45] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/18/2016] [Accepted: 04/25/2016] [Indexed: 01/05/2023] Open
Abstract
Cardiovascular protein therapeutics such as neuregulin (NRG1) and acidic-fibroblast growth factor (FGF1) requires new formulation strategies that allow for sustained bioavailability of the drug in the infarcted myocardium. However, there is no FDA-approved injectable protein delivery platform due to translational concerns about biomaterial administration through cardiac catheters. We therefore sought to evaluate the efficacy of percutaneous intramyocardial injection of poly(lactic-co-glycolic acid) microparticles (MPs) loaded with NRG1 and FGF1 using the NOGA MYOSTAR injection catheter in a porcine model of ischemia-reperfusion. NRG1- and FGF1-loaded MPs were prepared using a multiple emulsion solvent-evaporation technique. Infarcted pigs were treated one week after ischemia-reperfusion with MPs containing NRG1, FGF1 or non-loaded MPs delivered via clinically-translatable percutaneous transendocardial-injection. Three months post-treatment, echocardiography indicated a significant improvement in systolic and diastolic cardiac function. Moreover, improvement in bipolar voltage and decrease in transmural infarct progression was demonstrated by electromechanical NOGA-mapping. Functional benefit was associated with an increase in myocardial vascularization and remodeling. These findings in a large animal model of ischemia-reperfusion demonstrate the feasibility and efficacy of using MPs as a delivery system for growth factors and provide strong evidence to move forward with clinical studies using therapeutic proteins combined with catheter-compatible biomaterials.
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Affiliation(s)
- Elisa Garbayo
- Department of Pharmacy and Pharmaceutical Technology, School of Pharmacy, University of Navarra, Pamplona, Spain
- Instituto de Investigacion Sanitaria de Navarra (IDISNA), Pamplona, Spain
| | - Juan José Gavira
- Instituto de Investigacion Sanitaria de Navarra (IDISNA), Pamplona, Spain
- Hematology, Cardiology and Cell Therapy, Clínica Universidad de Navarra and Foundation for Applied Medical Research, University of Navarra, Pamplona, Spain
| | - Manuel Garcia de Yebenes
- Instituto de Investigacion Sanitaria de Navarra (IDISNA), Pamplona, Spain
- Hematology, Cardiology and Cell Therapy, Clínica Universidad de Navarra and Foundation for Applied Medical Research, University of Navarra, Pamplona, Spain
| | - Beatriz Pelacho
- Instituto de Investigacion Sanitaria de Navarra (IDISNA), Pamplona, Spain
- Hematology, Cardiology and Cell Therapy, Clínica Universidad de Navarra and Foundation for Applied Medical Research, University of Navarra, Pamplona, Spain
| | - Gloria Abizanda
- Instituto de Investigacion Sanitaria de Navarra (IDISNA), Pamplona, Spain
- Hematology, Cardiology and Cell Therapy, Clínica Universidad de Navarra and Foundation for Applied Medical Research, University of Navarra, Pamplona, Spain
| | - Hugo Lana
- Department of Pharmacy and Pharmaceutical Technology, School of Pharmacy, University of Navarra, Pamplona, Spain
- Instituto de Investigacion Sanitaria de Navarra (IDISNA), Pamplona, Spain
| | - María José Blanco-Prieto
- Department of Pharmacy and Pharmaceutical Technology, School of Pharmacy, University of Navarra, Pamplona, Spain
- Instituto de Investigacion Sanitaria de Navarra (IDISNA), Pamplona, Spain
| | - Felipe Prosper
- Instituto de Investigacion Sanitaria de Navarra (IDISNA), Pamplona, Spain
- Hematology, Cardiology and Cell Therapy, Clínica Universidad de Navarra and Foundation for Applied Medical Research, University of Navarra, Pamplona, Spain
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30
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Affiliation(s)
- Margherita Giorgetti
- Department of Hand Surgery and Reconstructive Microsurgery, University of Pisa, Pisa, Italy; Department of Clinical and Experimental Medicine, Neurological Clinic, University of Pisa, Pisa, Italy
| | - Gabriele Siciliano
- Department of Hand Surgery and Reconstructive Microsurgery, University of Pisa, Pisa, Italy; Department of Clinical and Experimental Medicine, Neurological Clinic, University of Pisa, Pisa, Italy
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31
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Spartalis E, Tomos P, Moris D, Athanasiou A, Markakis C, Spartalis MD, Troupis T, Dimitroulis D, Perrea D. Role of platelet-rich plasma in ischemic heart disease: An update on the latest evidence. World J Cardiol 2015; 7:665-670. [PMID: 26516421 PMCID: PMC4620078 DOI: 10.4330/wjc.v7.i10.665] [Citation(s) in RCA: 20] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/25/2015] [Revised: 07/07/2015] [Accepted: 09/08/2015] [Indexed: 02/06/2023] Open
Abstract
Myocardial infarction is the most common cause of congestive heart failure. Novel strategies such as directly reprogramming cardiac fibroblasts into cardiomyocytes are an exciting area of investigation for repair of injured myocardial tissue. The ultimate goal is to rebuild functional myocardium by transplanting exogenous stem cells or by activating native stem cells to induce endogenous repair. Cell-based myocardial restoration, however, has not penetrated broad clinical practice yet. Platelet-rich plasma, an autologous fractionation of whole blood containing high concentrations of growth factors, has been shown to safely and effectively enhance healing and angiogenesis primarily by reparative cell signaling. In this review, we collected all recent advances in novel therapies as well as experimental evidence demonstrating the role of platelet-rich plasma in ischemic heart disease, focusing on aspects that might be important for future successful clinical application.
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