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Meretsky CR, Polychronis A, Liovas D, Schiuma AT. Advances in Tissue Engineering and Its Future in Regenerative Medicine Compared to Traditional Reconstructive Techniques: A Comparative Analysis. Cureus 2024; 16:e68872. [PMID: 39376883 PMCID: PMC11457798 DOI: 10.7759/cureus.68872] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 09/06/2024] [Indexed: 10/09/2024] Open
Abstract
Tissue engineering represents a revolutionary approach in regenerative medicine, offering promising alternatives to traditional reconstructive techniques. This systematic review explores recent advances in tissue engineering, comparing their efficacy, postoperative outcomes, and patient satisfaction to conventional methods. A comprehensive literature search was conducted across PubMed, Cochrane Library, and Google Scholar, covering studies published from 2000 to 2024. Fourteen studies were selected for final analysis based on inclusion criteria focusing on outcomes such as scar quality, postoperative pain, and patient satisfaction. The review demonstrated that tissue engineering techniques consistently provided superior cosmetic outcomes with minimal scarring compared to traditional methods. Patients undergoing tissue-engineered procedures experienced mild-to-moderate postoperative pain with rapid resolution, whereas traditional techniques resulted in moderate to severe pain requiring extended management. Furthermore, patients treated with tissue engineering reported high satisfaction rates due to improved cosmetic and functional outcomes. Despite challenges such as ensuring adequate vascularization, controlling scaffold degradation, and overcoming regulatory and cost barriers, ongoing research and development are essential to fully realize the potential of these innovative therapies. Tissue engineering offers significant advantages over traditional reconstructive techniques and has the potential to profoundly improve patient care in regenerative medicine.
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Affiliation(s)
| | - Andreas Polychronis
- General Surgery, St. George's University School of Medicine, Great River, USA
| | - Dimitria Liovas
- Medicine, St. George's University School of Medicine, Great River, USA
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2
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Ding H, Hou X, Gao Z, Guo Y, Liao B, Wan J. Challenges and Strategies for Endothelializing Decellularized Small-Diameter Tissue-Engineered Vessel Grafts. Adv Healthc Mater 2024; 13:e2304432. [PMID: 38462702 DOI: 10.1002/adhm.202304432] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/13/2023] [Revised: 02/26/2024] [Indexed: 03/12/2024]
Abstract
Vascular diseases are the leading cause of ischemic necrosis in tissues and organs, necessitating using vascular grafts to restore blood supply. Currently, small vessels for coronary artery bypass grafts are unavailable in clinical settings. Decellularized small-diameter tissue-engineered vessel grafts (SD-TEVGs) hold significant potential. However, they face challenges, as simple implantation of decellularized SD-TEVGs in animals leads to thrombosis and calcification due to incomplete endothelialization. Consequently, research and development focus has shifted toward enhancing the endothelialization process of decellularized SD-TEVGs. This paper reviews preclinical studies involving decellularized SD-TEVGs, highlighting different strategies and their advantages and disadvantages for achieving rapid endothelialization of these vascular grafts. Methods are analyzed to improve the process while addressing potential shortcomings. This paper aims to contribute to the future commercial viability of decellularized SD-TEVGs.
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Affiliation(s)
- Heng Ding
- Department of Cardiovascular Surgery, The Affiliated Hospital, Southwest Medical University, Metabolic Vascular Diseases Key Laboratory of Sichuan Province, Key Laboratory of cardiovascular remodeling and dysfunction, Luzhou, Sichuan, 646000, China
- Nanjing Medical University, Nanjing, 211166, P. R. China
| | - Xiaojie Hou
- Department of Cardiovascular Surgery and Cardiovascular Surgery Research Laboratory, West China Hospital, Sichuan University, Chengdu, Sichuan, 610041, China
| | - Zhen Gao
- Department of Cardiac Surgery, Beijing Anzhen Hospital, Capital Medical University, Beijing, 100069, China
| | - Yingqiang Guo
- Department of Cardiovascular Surgery and Cardiovascular Surgery Research Laboratory, West China Hospital, Sichuan University, Chengdu, Sichuan, 610041, China
| | - Bin Liao
- Department of Cardiovascular Surgery, The Affiliated Hospital, Southwest Medical University, Metabolic Vascular Diseases Key Laboratory of Sichuan Province, Key Laboratory of cardiovascular remodeling and dysfunction, Luzhou, Sichuan, 646000, China
- Key Laboratory of Medical Electrophysiology, Ministry of Education & Medical Electrophysiological Key Laboratory of Sichuan Province, (Collaborative Innovation Center for Prevention of Cardiovascular Diseases), Institute of Cardiovascular Research, Southwest Medical University, Luzhou, Sichuan, 646000, China
| | - Juyi Wan
- Department of Cardiovascular Surgery, The Affiliated Hospital, Southwest Medical University, Metabolic Vascular Diseases Key Laboratory of Sichuan Province, Key Laboratory of cardiovascular remodeling and dysfunction, Luzhou, Sichuan, 646000, China
- Key Laboratory of Medical Electrophysiology, Ministry of Education & Medical Electrophysiological Key Laboratory of Sichuan Province, (Collaborative Innovation Center for Prevention of Cardiovascular Diseases), Institute of Cardiovascular Research, Southwest Medical University, Luzhou, Sichuan, 646000, China
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3
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Current Progress in Vascular Engineering and Its Clinical Applications. Cells 2022; 11:cells11030493. [PMID: 35159302 PMCID: PMC8834640 DOI: 10.3390/cells11030493] [Citation(s) in RCA: 15] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/09/2022] [Revised: 01/28/2022] [Accepted: 01/29/2022] [Indexed: 02/04/2023] Open
Abstract
Coronary heart disease (CHD) is caused by narrowing or blockage of coronary arteries due to atherosclerosis. Coronary artery bypass grafting (CABG) is widely used for the treatment of severe CHD cases. Although autologous vessels are a preferred choice, healthy autologous vessels are not always available; hence there is a demand for tissue engineered vascular grafts (TEVGs) to be used as alternatives. However, producing clinical grade implantable TEVGs that could healthily survive in the host with long-term patency is still a great challenge. There are additional difficulties in producing small diameter (<6 mm) vascular conduits. As a result, there have not been TEVGs that are commercially available. Properties of vascular scaffolds such as tensile strength, thrombogenicity and immunogenicity are key factors that determine the biocompatibility of TEVGs. The source of vascular cells employed to produce TEVGs is a limiting factor for large-scale productions. Advanced technologies including the combined use of natural and biodegradable synthetic materials for scaffolds in conjunction with the use of mesenchyme stem cells or induced pluripotent stem cells (iPSCs) provide promising solutions for vascular tissue engineering. The aim of this review is to provide an update on various aspects in this field and the current status of TEVG clinical applications.
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Platoff R, Villalobos MA, Hagaman AR, Liu Y, Matthews M, DiSanto ME, Carpenter JP, Zhang P. Effects of radiation and chemotherapy on adipose stem cells: Implications for use in fat grafting in cancer patients. World J Stem Cells 2021; 13:1084-1093. [PMID: 34567427 PMCID: PMC8422936 DOI: 10.4252/wjsc.v13.i8.1084] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/25/2021] [Revised: 04/30/2021] [Accepted: 07/29/2021] [Indexed: 02/06/2023] Open
Abstract
Autologous fat transplantation is a versatile tool in reconstructive surgery. Adipose-derived stem cells (ASCs) increase survival of fat grafts and thus are increasingly used for breast reconstruction in breast cancer patients. However, radiation and/or chemotherapy have been proposed to inhibit soft tissue regeneration in wound healing thus suggesting alteration in stem cell pathways. Therefore, elucidating effects of radiation and chemotherapy on ASCs is critical if one desires to enhance the survival of fat grafts in patients. This review outlines our work evaluating the function and recoverability of ASCs from radiation or chemotherapy patients, focusing specifically on their availability as a source of autologous stem cells for fat grafting and breast reconstruction in cancer patients. Even though evidence suggests radiation and chemotherapy negatively influence ASCs at the cellular level, the efficiency of the isolation and differentiation capacity did not appear influenced in patients after receiving chemotherapy treatment, although fat from radiated patients exhibited significantly altered ASC differentiation into endothelial-like cells. Further, the in vitro growth rates of patient’s ASCs do not differ significantly before or after treatment. Taken together, these studies suggest ASCs as an important new tool for grafting and reconstruction even when radiation and chemotherapy treatment are involved.
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Affiliation(s)
- Rebecca Platoff
- Department of Surgery, Cooper University Health Care, Camden, NJ 08103, United States
| | - Miguel A Villalobos
- Department of Surgery, Cooper University Health Care, Camden, NJ 08103, United States
| | - Ashleigh Rapp Hagaman
- Department of Surgery, Cooper University Health Care, Camden, NJ 08103, United States
| | - Yuan Liu
- Department of Surgery, Cooper University Health Care, Camden, NJ 08103, United States
- Department of Surgery, Cooper Medical School of Rowan University, Camden, NJ 08103, United States
| | - Martha Matthews
- Department of Surgery, Cooper University Health Care, Camden, NJ 08103, United States
- Department of Surgery, Cooper Medical School of Rowan University, Camden, NJ 08103, United States
| | - Michael E DiSanto
- Department of Biomedical Sciences, Cooper Medical School of Rowan University, Camden, NJ 08103, United States
| | - Jeffrey P Carpenter
- Department of Surgery, Cooper University Health Care, Camden, NJ 08103, United States
- Department of Surgery, Cooper Medical School of Rowan University, Camden, NJ 08103, United States
| | - Ping Zhang
- Department of Surgery, Cooper University Health Care, Camden, NJ 08103, United States
- Department of Surgery, Cooper Medical School of Rowan University, Camden, NJ 08103, United States
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5
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Khazaei S, Khademi A, Nasr Esfahani MH, Khazaei M, Nekoofar MH, Dummer PMH. Isolation and Differentiation of Adipose-Derived Stem Cells into Odontoblast-Like Cells: A Preliminary In Vitro Study. CELL JOURNAL 2021; 23:288-293. [PMID: 34308571 PMCID: PMC8286457 DOI: 10.22074/cellj.2021.7325] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 12/15/2019] [Accepted: 01/21/2020] [Indexed: 11/04/2022]
Abstract
Objective The aim of present study was to isolate and differentiate human adipose-derived stem cells (ASCs) into odontoblast-like cells. Materials and Methods In this experimental study, human adipose tissues were taken from the buccal fat pad of three individuals (mean age: 24.6 ± 2.1 years). The tissues were transferred to a laboratory in a sterile culture medium, divided into small pieces and digested by collagenase I (2 mg/mL, 60-90 minutes). ASCs were isolated by passing the cell suspension through cell strainers (70 and 40 μm), followed by incubation at 37ºC and 5% CO2 in Dulbecco's modified eagle medium (DMEM) supplemented with fetal bovine serum (FBS 5%) and penicillin/streptomycin (P/S). After three passages, the ASCs were harvested. Subsequently, flow cytometry and reverse transcriptase polymerase chain reaction (RT-PCR) were used to detect expression levels of NANOG and OCT4 to evaluate stemness. Then, a differentiation medium that included high-glucose DMEM supplemented with 10% FBS, dexamethasone (10 nM), sodium β-glycerophosphate (5 mM) and ascorbic acid (100 μM) was added. The cells were cultivated for four weeks, and the odontogenic medium was changed every two days. Cell differentiation was evaluated with Alizarin red staining and expressions of collagen I (COL1A1), dentin sialophosphoprotein (DSPP) and dentin matrix protein-1 (DMP1). Results The ASCs were effectively and easily isolated. They were negative for CD45 and positive for the CD105 and CD73 markers. The ASCs expressed OCT4 and NANOG. Differentiated cells highly expressed DSPP, COL1A1 and DMP1. Alizarin red staining revealed a positive reaction for calcium deposition. Conclusion ASCs were isolated successfully in high numbers from the buccal fat pad of human volunteers and were differentiated into odontoblast-like cells. These ASCs could be considered a new source of cells for use in regenerative endodontic treatments.
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Affiliation(s)
- Saber Khazaei
- Department of Endodontics, School of Dentistry and Dental Research Centre, Dental Research Institute, Isfahan University of Medical Sciences, Isfahan, Iran.,Department of Endodontics, School of Dentistry, Kermanshah University of Medical Sciences, Kermanshah, Iran
| | - Abbasali Khademi
- Department of Endodontics, School of Dentistry and Dental Research Centre, Dental Research Institute, Isfahan University of Medical Sciences, Isfahan, Iran.
| | - Mohammad Hossein Nasr Esfahani
- Department of Animal Biotechnology, Reproductive Biomedicine Research Center, Royan Institute for Biotechnology, ACECR, Isfahan, Iran
| | - Mozafar Khazaei
- Fertility and Infertility Research Centre, Health Technology Institute, Kermanshah University of Medical Sciences, Kermanshah, Iran.
| | | | - Paul M H Dummer
- School of Dentistry, College of Biomedical and Life Sciences, Cardiff University, Cardiff, UK
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Khazaei S, Khademi A, Torabinejad M, Nasr Esfahani MH, Khazaei M, Razavi SM. Improving pulp revascularization outcomes with buccal fat autotransplantation. J Tissue Eng Regen Med 2020; 14:1227-1235. [PMID: 32610370 DOI: 10.1002/term.3094] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/25/2020] [Revised: 06/28/2020] [Accepted: 06/29/2020] [Indexed: 11/12/2022]
Abstract
Several techniques have been introduced to improve the pulp revascularization outcomes. The use of the tissue graft can create more practical tissue regeneration, provide vascular supply, and enhance tissue healing. The aim of the present study was to investigate the histologic and molecular outcomes of pulp revascularization with buccal fat autotransplantation. Fifty-six open apex roots from four dogs aged 4-6 months were randomly allocated to five groups of endodontic regeneration models: Group 1 (negative control, n = 4); Group 2 (control and without intervention, n = 4); Group 3 (blood clot, n = 16); Group 4 (buccal fat autotransplantation, n = 16); and Group 5 (blood clot plus buccal fat autotransplantation, n = 16). After 3 months, the extracted dog teeth were analyzed by histological and immunohistochemical techniques. Furthermore, real-time quantitative polymerase chain reactions were implemented to assess the gene expression profiles of dentin sialophosphoprotein (DSPP), dentin matrix protein (DMP), collagen I (COL1), and alkaline phosphatase (ALP) on regenerated tissue in the root canals. There were no significant differences in the severity of inflammation and necrosis between intervention groups. Immunohistochemical analysis showed significant differences among the study groups in expression level of extracellular glycoproteins such as fibronectin, laminin, and tenascin C. Group 5 showed an increase in the expression of DMP1 and COL1 genes. The expression of DSPP gene increased significantly in Group 4. The expression of ALP gene increased significantly in Group 3. Using this procedure may open new fields of research for regenerative endodontic procedure in which tissue autotransplant, particularly adipose tissue, may improve the outcomes of pulp revascularization.
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Affiliation(s)
- Saber Khazaei
- Department of Endodontics and Dental Research Center, Dental Research Institute, Isfahan University of Medical Sciences, Isfahan, Iran
| | - Abbasali Khademi
- Department of Endodontics and Dental Research Center, Dental Research Institute, Isfahan University of Medical Sciences, Isfahan, Iran
| | | | - Mohammad H Nasr Esfahani
- Department of Animal Biotechnology, Reproductive Biomedicine Research Center, Royan Institute for Biotechnology, ACECR, Isfahan, Iran
| | - Mozafar Khazaei
- Fertility and Infertility Research Center, Health Technology Institute, Kermanshah University of Medical Sciences, Kermanshah, Iran
| | - Sayed Mohammad Razavi
- Department of Oral and Maxillofacial Pathology and Dental Implant Research Center, Dental Research Institute, Isfahan University of Medical Sciences, Isfahan, Iran
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7
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Lin CH, Lu JH, Hsia K, Lee H, Yao CL, Ma H. The Antithrombotic Function of Sphingosine-1-Phosphate on Human Adipose-Stem-Cell-Recellularized Tissue Engineered Vascular Graft In Vitro. Int J Mol Sci 2019; 20:ijms20205218. [PMID: 31640220 PMCID: PMC6829437 DOI: 10.3390/ijms20205218] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/26/2019] [Revised: 10/11/2019] [Accepted: 10/17/2019] [Indexed: 12/26/2022] Open
Abstract
Adipose stem cells (ASCs) show potential in the recellularization of tissue engineerined vascular grafts (TEVGs). However, whether sphingosine-1-phosphate (S1P) could further enhance the adhesion, proliferation, and antithrombosis of ASCs on decellularized vascular scaffolds is unknown. This study investigated the effect of S1P on the recellularization of TEVGs with ASCs. Human ASCs were derived from lipoaspirate. Scaffolds were derived from human umbilical arteries (HUAs) with treatment of 0.1% sodium dodecyl sulfate (SDS) for 48 h (decellularized HUAs; DHUAs). The adhesion, proliferation, and antithrombotic functions (kinetic clotting time and platelet adhesion) of ASCs on DHUAs with S1P or without S1P were evaluated. The histology and DNA examination revealed a preserved structure and the elimination of the nuclear component more than 95% in HUAs after decellularizaiton. Human ASCs (hASCs) showed CD29(+), CD73(+), CD90(+), CD105(+), CD31(-), CD34(-), CD44(-), HLA-DR(-), and CD146(-) while S1P-treated ASCs showed marker shifting to CD31(+). In contrast to human umbilical vein endothelial cells (HUVECs), S1P didn't significantly increase proliferation of ASCs on DHUAs. However, the kinetic clotting test revealed prolonged blood clotting in S1P-treated ASC-recellularized DHUAs. S1P also decreased platelet adhesion on ASC-recellularized DHUAs. In addition, S1P treatment increased the syndecan-1 expression of ASCs. TEVG reconstituted with S1P and ASC-recellularized DHUAs showed an antithrombotic effect in vitro. The preliminary results showed that ASCs could adhere to DHUAs and S1P could increase the antithrombotic effect on ASC-recellularized DHUAs. The antithrombotic effect is related to ASCs exhibiting an endothelial-cell-like function and preventing of syndecan-1 shedding. A future animal study is warranted to prove this novel method.
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Affiliation(s)
- Chih-Hsun Lin
- Division of Plastic and Reconstructive Surgery, Department of Surgery, Taipei Veterans General Hospital, Taipei 11217, Taiwan.
- Department of Surgery, School of Medicine, National Yang-Ming University, Taipei 11221, Taiwan.
| | - Jen-Her Lu
- Department of Pediatrics, Taipei Veterans General Hospital, Taipei 11217, Taiwan.
- Department of Surgery, medicine & Pediatrics, School of Medicine, National Defense Medical Center, Taipei 11490, Taiwan.
- Department of Pediatrics, School of Medicine, National Yang-Ming University, Taipei 11221, Taiwan.
| | - Kai Hsia
- Department of Pediatrics, Taipei Veterans General Hospital, Taipei 11217, Taiwan.
- Department of Life Science, National Taiwan University, Taipei 10617, Taiwan.
| | - Hsinyu Lee
- Department of Life Science, National Taiwan University, Taipei 10617, Taiwan.
| | - Chao-Ling Yao
- Department of Chemical Engineering and Materials Science, Graduate School of Biotechnology and Bioengineering, Yuan Ze University, Chung-Li, Taoyuan City 32003, Taiwan.
| | - Hsu Ma
- Division of Plastic and Reconstructive Surgery, Department of Surgery, Taipei Veterans General Hospital, Taipei 11217, Taiwan.
- Department of Surgery, School of Medicine, National Yang-Ming University, Taipei 11221, Taiwan.
- Department of Surgery, medicine & Pediatrics, School of Medicine, National Defense Medical Center, Taipei 11490, Taiwan.
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Arora S, Yim EKF, Toh YC. Environmental Specification of Pluripotent Stem Cell Derived Endothelial Cells Toward Arterial and Venous Subtypes. Front Bioeng Biotechnol 2019; 7:143. [PMID: 31259171 PMCID: PMC6587665 DOI: 10.3389/fbioe.2019.00143] [Citation(s) in RCA: 14] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/25/2019] [Accepted: 05/28/2019] [Indexed: 12/25/2022] Open
Abstract
Endothelial cells (ECs) are required for a multitude of cardiovascular clinical applications, such as revascularization of ischemic tissues or endothelialization of tissue engineered grafts. Patient derived primary ECs are limited in number, have donor variabilities and their in vitro phenotypes and functions can deteriorate over time. This necessitates the exploration of alternative EC sources. Although there has been a recent surge in the use of pluripotent stem cell derived endothelial cells (PSC-ECs) for various cardiovascular clinical applications, current differentiation protocols yield a heterogeneous EC population, where their specification into arterial or venous subtypes is undefined. Since arterial and venous ECs are phenotypically and functionally different, inappropriate matching of exogenous ECs to host sites can potentially affect clinical efficacy, as exemplified by venous graft mismatch when placed into an arterial environment. Therefore, there is a need to design and employ environmental cues that can effectively modulate PSC-ECs into a more homogeneous arterial or venous phenotype for better adaptation to the host environment, which will in turn contribute to better application efficacy. In this review, we will first give an overview of the developmental and functional differences between arterial and venous ECs. This provides the foundation for our subsequent discussion on the different bioengineering strategies that have been investigated to varying extent in providing biochemical and biophysical environmental cues to mature PSC-ECs into arterial or venous subtypes. The ability to efficiently leverage on a combination of biochemical and biophysical environmental cues to modulate intrinsic arterio-venous specification programs in ECs will greatly facilitate future translational applications of PSC-ECs. Since the development and maintenance of arterial and venous ECs in vivo occur in disparate physio-chemical microenvironments, it is conceivable that the application of these environmental factors in customized combinations or magnitudes can be used to selectively mature PSC-ECs into an arterial or venous subtype.
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Affiliation(s)
- Seep Arora
- Department of Biomedical Engineering, National University of Singapore, Singapore, Singapore.,Singapore Institute for Neurotechnology (SINAPSE), National University of Singapore, Singapore, Singapore
| | - Evelyn K F Yim
- Department of Chemical Engineering, University of Waterloo, Waterloo, ON, Canada
| | - Yi-Chin Toh
- Department of Biomedical Engineering, National University of Singapore, Singapore, Singapore.,Singapore Institute for Neurotechnology (SINAPSE), National University of Singapore, Singapore, Singapore.,Biomedical Institute for Global Health Research and Technology (BIGHEART), National University of Singapore, Singapore, Singapore.,NUS Tissue Engineering Program, National University of Singapore, Singapore, Singapore
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10
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Saberianpour S, Heidarzadeh M, Geranmayeh MH, Hosseinkhani H, Rahbarghazi R, Nouri M. Tissue engineering strategies for the induction of angiogenesis using biomaterials. J Biol Eng 2018; 12:36. [PMID: 30603044 PMCID: PMC6307144 DOI: 10.1186/s13036-018-0133-4] [Citation(s) in RCA: 79] [Impact Index Per Article: 11.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/10/2018] [Accepted: 12/13/2018] [Indexed: 02/07/2023] Open
Abstract
Angiogenesis is touted as a fundamental procedure in the regeneration and restoration of different tissues. The induction of de novo blood vessels seems to be vital to yield a successful cell transplantation rate loaded on various scaffolds. Scaffolds are natural or artificial substances that are considered as one of the means for delivering, aligning, maintaining cell connection in a favor of angiogenesis. In addition to the potential role of distinct scaffold type on vascularization, the application of some strategies such as genetic manipulation, and conjugation of pro-angiogenic factors could intensify angiogenesis potential. In the current review, we focused on the status of numerous scaffolds applicable in the field of vascular biology. Also, different strategies and priming approaches useful for the induction of pro-angiogenic signaling pathways were highlighted.
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Affiliation(s)
- Shirin Saberianpour
- 1Stem Cell Research Center, Tabriz University of Medical Sciences, Imam Reza St., Golgasht St, Tabriz, 5166614756 Iran
- 2Department of Molecular Medicine, Faculty of Advanced Medical Sciences, Tabriz University of Medical Sciences, Tabriz, Iran
| | - Morteza Heidarzadeh
- 1Stem Cell Research Center, Tabriz University of Medical Sciences, Imam Reza St., Golgasht St, Tabriz, 5166614756 Iran
| | - Mohammad Hossein Geranmayeh
- 3Neuroscience Research Center, Imam Reza Medical Center, Tabriz University of Medical Sciences, Tabriz, Iran
| | | | - Reza Rahbarghazi
- 1Stem Cell Research Center, Tabriz University of Medical Sciences, Imam Reza St., Golgasht St, Tabriz, 5166614756 Iran
- 5Department of Applied Cell Sciences, Faculty of Advanced Medical Sciences, Tabriz University of Medical Sciences, Tabriz, Iran
| | - Mohammad Nouri
- 2Department of Molecular Medicine, Faculty of Advanced Medical Sciences, Tabriz University of Medical Sciences, Tabriz, Iran
- 1Stem Cell Research Center, Tabriz University of Medical Sciences, Imam Reza St., Golgasht St, Tabriz, 5166614756 Iran
- 5Department of Applied Cell Sciences, Faculty of Advanced Medical Sciences, Tabriz University of Medical Sciences, Tabriz, Iran
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11
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Dhulekar J, Simionescu A. Challenges in vascular tissue engineering for diabetic patients. Acta Biomater 2018; 70:25-34. [PMID: 29396167 PMCID: PMC5871600 DOI: 10.1016/j.actbio.2018.01.008] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/12/2017] [Revised: 01/06/2018] [Accepted: 01/09/2018] [Indexed: 12/16/2022]
Abstract
Hyperglycemia and dyslipidemia coexist in diabetes and result in inflammation, degeneration, and impaired tissue remodeling, processes which are not conducive to the desired integration of tissue engineered products into the surrounding tissues. There are several challenges for vascular tissue engineering such as non-thrombogenicity, adequate burst pressure and compliance, suturability, appropriate remodeling responses, and vasoactivity, but, under diabetic conditions, an additional challenge needs to be considered: the aggressive oxidative environment generated by the high glucose and lipid concentrations that lead to the formation of advanced glycation end products (AGEs) in the vascular wall. Extracellular matrix-based scaffolds have adequate physical properties and are biocompatible, however, these scaffolds are altered in diabetes by the formation AGEs and impaired collagen degradation, consequently increasing vascular wall stiffness. In addition, vascular cells detect and respond to altered stimuli from the matrix by pathological remodeling of the vascular wall. Due to the immunomodulatory effects of mesenchymal stem cells (MSCs), they are frequently used in tissue engineering in order to protect the scaffolds from inflammation. MSCs together with antioxidant treatments of the scaffolds are expected to protect the vascular grafts from diabetes-induced alterations. In conclusion, as one of the most daunting environments that could damage the ECM and its interaction with cells is progressively built in diabetes, we recommend that cells and scaffolds used in vascular tissue engineering for diabetic patients are tested in diabetic animal models, in order to obtain valuable results regarding their resistance to diabetic adversities. STATEMENT OF SIGNIFICANCE Almost 25 million Americans have diabetes, characterized by high levels of blood sugar that binds to tissues and disturbs the function of cardiovascular structures. Therefore, patients with diabetes have a high risk of cardiovascular diseases. Surgery is required to replace diseased arteries with implants, but these fail after 5-10 years because they are made of non-living materials, not resistant to diabetes. New tissue engineering materials are developed, based on the patients' own stem cells, isolated from fat, and added to extracellular matrix-based scaffolds. Our main concern is that diabetes could damage the tissue-like implants. Thus we review studies related to the effect of diabetes on tissue components and recommend antioxidant treatments to increase the resistance of implants to diabetes.
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12
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Gasser M, Frank MH, Waaga-Gasser AM. [Stem cell-based strategies in vascular surgery]. GEFASSCHIRURGIE 2018. [PMID: 29527101 DOI: 10.1007/s00772-017-0349-5] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 11/28/2022]
Abstract
Critical chronic ischemia in patients with underlying arterial occlusive disease requires vascular reconstructive surgery. The limited supply of suitable small-diameter autologous vascular grafts in many patients and obvious disadvantages of synthetic bypass material demand the development of clinically usable tissue-engineered blood vessel substitutes. Despite substantial progress in the field over the last two decades, their implementation into the clinical routine has been challenging. The limited replicative life span of human adult vascular cells and their slow rate of collagenous matrix production in vitro have posed important problems in the development of mechanically robust and biologically functional engineered grafts. With recent advances in stem cell research, new cell sources for vascular tissue engineering have become available. In particular, the discovery of human induced pluripotent stem (iPS) cells derived from adult differentiated cells, as well as of human multipotent adult mesenchymal stem cells without gene modification requirements and related safety concerns, may advance the development of novel autologous cell-based tissue engineering approaches. Here we discuss recent developments in the field of vascular progenitor cells and opportunities and challenges for the clinical translation of stem cell-engineered vascular tissue substitutes.
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Affiliation(s)
- M Gasser
- Chirurgische Klinik I, Universitätsklinikum Würzburg, Würzburg, Deutschland
| | - M H Frank
- Transplant Research Program, Boston Children's Hospital, Harvard Medical School, Boston, USA.,School of Medical and Health Sciences, Edith Cowan University, Perth, Australien
| | - A M Waaga-Gasser
- Chirurgische Klinik I, Molekulare Onkologie und Immunologie, Universitätsklinikum Würzburg, Würzburg, Deutschland.,Transplantation Research Center, Brigham and Women's Hospital, Harvard Medical School, Boston, USA
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13
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Wang F, Zhang J, Wang R, Gu Y, Li J, Wang C. Triton X-100 combines with chymotrypsin: A more promising protocol to prepare decellularized porcine carotid arteries. Biomed Mater Eng 2017; 28:531-543. [PMID: 28854493 DOI: 10.3233/bme-171694] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/15/2022]
Abstract
BACKGROUND Morbidity and mortality of cardiovascular diseases are increasing in recent years. To solve these problems, vascular transplantation has become a common approach. Decellularization has been a hot spot of tissue engineering to prepare vessel substitutes for vascular transplantation. However, there is no established canonical protocol for decellularization thus far. OBJECTIVE To further understand the decellularization effect of decellularization protocols and the causal relationship between decellularization and mechanical properties. METHODS Three decellularization protocols including two chemical protocols based on SDS and Trypsin respectively and a combination of Triton X-100 with chymotrypsin were adopted to obtain decellularized porcine carotid arteries in our study. After decellularization, histological analysis, scanning electron microscopy and mechanical tests were performed to evaluate their efficiency on removing of cellular components, retention of extracellular matrix and influence on mechanical properties. RESULTS All these decellularization protocols used in our study were efficient to remove cellular components. However, SDS and trypsin performed more disruptive effect on ECM structure and mechanical properties of native arteries while Triton X-100 combines with chymotrypsin had no significant disruptive effect. CONCLUSIONS Compared with decellularization protocols based on SDS and trypsin, Triton X-100 combines with chymotrypsin used in our study may be a more promising protocol to prepare decellularized porcine carotid arteries for vascular tissue engineering applications.
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Affiliation(s)
- Fei Wang
- Department of Vascular Surgery, Xuan Wu Hospital, Capital Medical University, Beijing, P.R. China.,Institute of Vascular Surgery, Capital Medical University, Beijing, P.R. China
| | - Jian Zhang
- Department of Vascular Surgery, Xuan Wu Hospital, Capital Medical University, Beijing, P.R. China.,Institute of Vascular Surgery, Capital Medical University, Beijing, P.R. China
| | - Rong Wang
- Department of Central Laboratory, Xuan Wu Hospital, Capital Medical University, Beijing, P.R. China
| | - Yongquan Gu
- Department of Vascular Surgery, Xuan Wu Hospital, Capital Medical University, Beijing, P.R. China.,Institute of Vascular Surgery, Capital Medical University, Beijing, P.R. China
| | - Jianxin Li
- Department of Vascular Surgery, Xuan Wu Hospital, Capital Medical University, Beijing, P.R. China.,Institute of Vascular Surgery, Capital Medical University, Beijing, P.R. China
| | - Cong Wang
- Department of Vascular Surgery, Xuan Wu Hospital, Capital Medical University, Beijing, P.R. China.,Institute of Vascular Surgery, Capital Medical University, Beijing, P.R. China
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Tseng YC, Roan JN, Ho YC, Lin CC, Yeh ML. An in vivo study on endothelialized vascular grafts produced by autologous biotubes and adipose stem cells (ADSCs). JOURNAL OF MATERIALS SCIENCE. MATERIALS IN MEDICINE 2017; 28:166. [PMID: 28914400 DOI: 10.1007/s10856-017-5986-4] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 03/10/2017] [Accepted: 09/04/2017] [Indexed: 06/07/2023]
Abstract
Currently, commercial synthetic vascular grafts made from Dacron and ePTFE for small-diameter, vascular applications (<6 mm) show limited reendothelization and are less compliant, often resulting in thrombosis and intimal hyperplasia. Although good blood compatibility can be achieved in autologous arteries and veins, the number of high quality harvest sites is limited, and the grafts are size-mismatched for use in the fistula or cardiovascular bypass surgery; thus, alternative small graft substitutes must be developed. A biotube is an in vivo, tissue-engineered approach for the growth of autologous grafts through the subcutaneous implantation of an inert rod through the inflammation process. In the present study, we embedded silicone rods with a diameter of 2 mm into the dorsal subcutaneous tissue of rabbits for 4 weeks to grow biotubes. The formation of functional endothelium cells aligned on the inner wall surface was achieved by seeding with adipose stem cells (ADSCs). The ADSCs-seeded biotubes were implanted into the carotid artery of rabbits for more than 1 month, and the patency rates and remodeling of endothelial cells were observed by angiography and fluorescence staining, respectively. Finally, the mechanical properties of the biotube were also evaluated. The fluorescence staining results showed that the ADSCs differentiated not only into endothelia cells but also into smooth muscle cells. Moreover, the patency of the ADSCs-seeded biotube remained high for at least 5 months. These small-sized ADSCs-seeded vascular biotubes may decrease the rate of intimal hyperplasia during longer implantation times and have potential clinical applications in the future.
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Affiliation(s)
- Yu Chieh Tseng
- Department of Biomedical Engineering, National Cheng Kung University, Tainan, Taiwan
| | - Jun Neng Roan
- Institute of clinical medicine, National Cheng Kung University, Tainan, Taiwan
- Division of Cardiovascular Surger, Department of Surgery, National Cheng Kung University College of Medicine and Hospital, Tainan, Taiwan
| | - Ying Chiang Ho
- Department of Biomedical Engineering, National Cheng Kung University, Tainan, Taiwan
| | - Chih Chan Lin
- Department of Medical Research, Laboratory Animal Center, Chi-Mei Medical Center, Tainan, Taiwan
| | - Ming Long Yeh
- Department of Biomedical Engineering, National Cheng Kung University, Tainan, Taiwan.
- Medical Device Innovation Center, National Cheng Kung University, Tainan, Taiwan.
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15
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Xu ZC, Zhang Q, Li H. Engineering of the human vessel wall with hair follicle stem cells in vitro. Mol Med Rep 2016; 15:417-422. [PMID: 27959397 DOI: 10.3892/mmr.2016.6013] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/28/2015] [Accepted: 10/11/2016] [Indexed: 11/05/2022] Open
Abstract
Hair follicle stem cells (HFSCs) are increasingly used as a stem cell paradigm in vascular tissue engineering due to the fact that they are a rich source of easily accessible multipotent adult stem cells. Promising results have been demonstrated with small diameter (less than 6 mm) tissue engineered blood vessels under low blood pressure, however engineering large vessels (>6 mm in diameter) remains a challenge due to the fact it demands a higher number of seed cells and higher quality biomechanical properties. The aim of the current study was to engineer a large vessel (6 mm in diameter) with differentiated smooth muscle cells (SMCs) induced from human (h)HFSCs using transforming growth factor‑β1 and platelet‑derived growth factor BB in combination with low‑serum culture medium. The cells were seeded onto polyglycolic acid and then wrapped around a silicone tube and further cultured in vitro. A round vessel wall was formed subsequent to 8 weeks of culture. Histological examination indicated that layers of smooth muscle‑like cells and collagenous fibres were oriented in the induced group. In contrast, disorganised cells and collagenous fibres were apparent in the undifferentiated group. The approach developed in the current study demonstrated potential for constructing large muscular vessels with differentiated SMCs induced from hHFSCs.
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Affiliation(s)
- Zhi-Cheng Xu
- Department of Plastic and Reconstructive Surgery, Shanghai 9th People's Hospital, Shanghai Jiaotong University School of Medicine, Shanghai 200011, P.R. China
| | - Qun Zhang
- Department of Plastic and Reconstructive Surgery, Shanghai 9th People's Hospital, Shanghai Jiaotong University School of Medicine, Shanghai 200011, P.R. China
| | - Hong Li
- Department of Life Information and Instrument Engineering, Hangzhou Electronic Science and Technology University, Hangzhou, Zhejiang 310058, P.R. China
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16
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Comparison of Endothelial Differentiation Capacities of Human and Rat Adipose-Derived Stem Cells. Plast Reconstr Surg 2016; 138:1231-1241. [DOI: 10.1097/prs.0000000000002791] [Citation(s) in RCA: 14] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/11/2022]
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17
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Zhang H, Yu N, Zhou Y, Ma H, Wang J, Ma X, Liu J, Huang J, An Y. Construction and characterization of osteogenic and vascular endothelial cell sheets from rat adipose-derived mesenchymal stem cells. Tissue Cell 2016; 48:488-95. [DOI: 10.1016/j.tice.2016.07.004] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/07/2016] [Revised: 07/22/2016] [Accepted: 07/22/2016] [Indexed: 12/31/2022]
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Hsia K, Yao CL, Chen WM, Chen JH, Lee H, Lu JH. Scaffolds and Cell-Based Tissue Engineering for Blood Vessel Therapy. Cells Tissues Organs 2016; 202:281-295. [PMID: 27548610 DOI: 10.1159/000448169] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 07/04/2016] [Indexed: 11/19/2022] Open
Abstract
The increasing morbidity of cardiovascular diseases in modern society has made it crucial to develop a small-caliber blood vessel. In the absence of appropriate autologous vascular grafts, an alternative prosthesis must be constructed for cardiovascular disease patients. The aim of this article is to describe the advances in making cell-seeded cardiovascular prostheses. It also discusses the combinations of types of scaffolds and cells, especially autologous stem cells, which are suitable for application in tissue-engineered vessels with the favorable properties of mechanical strength, antithrombogenicity, biocompliance, anti-inflammation, fatigue resistance and long-term durability. This article highlights the advancements in cellular tissue-engineered vessels in recent years.
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19
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Horikoshi-Ishihara H, Tobita M, Tajima S, Tanaka R, Oshita T, Tabata Y, Mizuno H. Coadministration of adipose-derived stem cells and control-released basic fibroblast growth factor facilitates angiogenesis in a murine ischemic hind limb model. J Vasc Surg 2015; 64:1825-1834.e1. [PMID: 26597457 DOI: 10.1016/j.jvs.2015.09.054] [Citation(s) in RCA: 18] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/01/2015] [Accepted: 09/18/2015] [Indexed: 01/30/2023]
Abstract
OBJECTIVE Adipose-derived stem cells (ASCs) have angiogenic potential owing to their differentiation into endothelial cells and their release of angiogenic growth factors to elicit paracrine effects. In addition, control-released basic fibroblast growth factor (bFGF) sustained with a gelatin hydrogel also supports effective angiogenesis. We sought to determine if coadministration of ASCs and control-released bFGF into murine ischemic limbs facilitates angiogenesis. METHODS Levels of growth factors in the conditioned media of ASCs cultured with or without control-released bFGF were measured by enzyme-linked immunosorbent assays. A murine ischemic hind limb model was generated and intramuscularly injected with the following: gelatin hydrogel (group 1), a high number of ASCs (group 2), control-released bFGF (group 3), a small number of ASCs and control-released bFGF (group 4), and a high number of ASCs and control-released bFGF (group 5). Macroscopic and microscopic vascular changes were evaluated until day 7 by laser Doppler perfusion imaging and histologic analyses, respectively. RESULTS Secretion of hepatocyte growth factor, vascular endothelial growth factor, and transforming growth factor-β1 was enhanced by control-released bFGF. Vascular improvement was achieved in groups 4 and 5 according to laser Doppler perfusion imaging. Hematoxylin and eosin staining and CD31 immunohistochemical staining demonstrated an increase in the vascular density, vessel diameter, and thickness of vessel walls in groups 4 and 5. Cells positively stained for CD146, α-smooth muscle actin, and transforming growth factor-β1 were observed around vessel walls in groups 4 and 5. CONCLUSIONS These findings suggest that coadministration of ASCs and control-released bFGF facilitates angiogenesis in terms of vessel maturation in a murine ischemic hind limb model.
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Affiliation(s)
- Hisako Horikoshi-Ishihara
- Department of Plastic and Reconstructive Surgery, Juntendo University School of Medicine, Tokyo, Japan
| | - Morikuni Tobita
- Department of Plastic and Reconstructive Surgery, Juntendo University School of Medicine, Tokyo, Japan
| | - Satoshi Tajima
- Department of Plastic and Reconstructive Surgery, Juntendo University School of Medicine, Tokyo, Japan
| | - Rica Tanaka
- Department of Plastic and Reconstructive Surgery, Juntendo University School of Medicine, Tokyo, Japan
| | - Takashi Oshita
- Department of Plastic and Reconstructive Surgery, Juntendo University School of Medicine, Tokyo, Japan
| | - Yasuhiko Tabata
- Department of Biomaterials, Institute for Frontier Medical Sciences, Kyoto University, Kyoto, Japan
| | - Hiroshi Mizuno
- Department of Plastic and Reconstructive Surgery, Juntendo University School of Medicine, Tokyo, Japan.
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Pashneh-Tala S, MacNeil S, Claeyssens F. The Tissue-Engineered Vascular Graft-Past, Present, and Future. TISSUE ENGINEERING PART B-REVIEWS 2015; 22:68-100. [PMID: 26447530 PMCID: PMC4753638 DOI: 10.1089/ten.teb.2015.0100] [Citation(s) in RCA: 489] [Impact Index Per Article: 48.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Indexed: 12/17/2022]
Abstract
Cardiovascular disease is the leading cause of death worldwide, with this trend predicted to continue for the foreseeable future. Common disorders are associated with the stenosis or occlusion of blood vessels. The preferred treatment for the long-term revascularization of occluded vessels is surgery utilizing vascular grafts, such as coronary artery bypass grafting and peripheral artery bypass grafting. Currently, autologous vessels such as the saphenous vein and internal thoracic artery represent the gold standard grafts for small-diameter vessels (<6 mm), outperforming synthetic alternatives. However, these vessels are of limited availability, require invasive harvest, and are often unsuitable for use. To address this, the development of a tissue-engineered vascular graft (TEVG) has been rigorously pursued. This article reviews the current state of the art of TEVGs. The various approaches being explored to generate TEVGs are described, including scaffold-based methods (using synthetic and natural polymers), the use of decellularized natural matrices, and tissue self-assembly processes, with the results of various in vivo studies, including clinical trials, highlighted. A discussion of the key areas for further investigation, including graft cell source, mechanical properties, hemodynamics, integration, and assessment in animal models, is then presented.
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Affiliation(s)
- Samand Pashneh-Tala
- Department of Materials Science and Engineering, Kroto Research Institute, University of Sheffield , Broad Lane, Sheffield, United Kingdom
| | - Sheila MacNeil
- Department of Materials Science and Engineering, Kroto Research Institute, University of Sheffield , Broad Lane, Sheffield, United Kingdom
| | - Frederik Claeyssens
- Department of Materials Science and Engineering, Kroto Research Institute, University of Sheffield , Broad Lane, Sheffield, United Kingdom
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21
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Abstract
Heart disease, including valve pathologies, is the leading cause of death worldwide. Despite the progress made thanks to improving transplantation techniques, a perfect valve substitute has not yet been developed: once a diseased valve is replaced with current technologies, the newly implanted valve still needs to be changed some time in the future. This situation is particularly dramatic in the case of children and young adults, because of the necessity of valve growth during the patient's life. Our review focuses on the current status of heart valve (HV) therapy and the challenges that must be solved in the development of new approaches based on tissue engineering. Scientists and physicians have proposed tissue-engineered heart valves (TEHVs) as the most promising solution for HV replacement, especially given that they can help to avoid thrombosis, structural deterioration and xenoinfections. Lastly, TEHVs might also serve as a model for studying human valve development and pathologies.
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22
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Vallières K, Laterreur V, Tondreau MY, Ruel J, Germain L, Fradette J, Auger FA. Human adipose-derived stromal cells for the production of completely autologous self-assembled tissue-engineered vascular substitutes. Acta Biomater 2015; 24:209-19. [PMID: 26086693 DOI: 10.1016/j.actbio.2015.06.011] [Citation(s) in RCA: 24] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/19/2014] [Revised: 04/16/2015] [Accepted: 06/09/2015] [Indexed: 12/13/2022]
Abstract
There is a clinical need for small-diameter vascular substitutes, notably for coronary and peripheral artery bypass procedures since these surgeries are limited by the availability of grafting material. This study reports the characterization of a novel autologous tissue-engineered vascular substitute (TEVS) produced in 10weeks exclusively from human adipose-derived stromal cells (ASC) self-assembly, and its comparison to an established model made from dermal fibroblasts (DF). Briefly, ASC and DF were cultured with ascorbate to form cell sheets subsequently rolled around a mandrel. These TEVS were further cultured as a maturation period before undergoing mechanical testing, histological analyses and endothelialization. No significant differences were measured in burst pressure, suture strength, failure load, elastic modulus and failure strain according to the cell type used to produce the TEVS. Indeed, ASC- and DF-TEVS both displayed burst pressures well above maximal physiological blood pressure. However, ASC-TEVS were 1.40-fold more compliant than DF-TEVS. The structural matrix, comprising collagens type I and III, fibronectin and elastin, was very similar in all TEVS although histological analysis showed a wavier and less dense collagen matrix in ASC-TEVS. This difference in collagen organization could explain their higher compliance. Finally, human umbilical vein endothelial cells (HUVEC) successfully formed a confluent endothelium on ASC and DF cell sheets, as well as inside ASC-TEVS. Our results demonstrated that ASC are an alternative cell source for the production of TEVS displaying good mechanical properties and appropriate endothelialization.
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Affiliation(s)
- Karine Vallières
- Centre de recherche en organogénèse expérimentale de l'Université Laval/LOEX, Division of Regenerative Medicine, CHU de Québec Research Centre - Université Laval, Québec, QC, Canada; Department of Surgery, Faculty of Medicine, Université Laval, Québec, QC, Canada
| | - Véronique Laterreur
- Centre de recherche en organogénèse expérimentale de l'Université Laval/LOEX, Division of Regenerative Medicine, CHU de Québec Research Centre - Université Laval, Québec, QC, Canada; Department of Mechanical Engineering, Faculty of Science and Engineering, Université Laval, Québec, QC, Canada
| | - Maxime Y Tondreau
- Centre de recherche en organogénèse expérimentale de l'Université Laval/LOEX, Division of Regenerative Medicine, CHU de Québec Research Centre - Université Laval, Québec, QC, Canada; Department of Surgery, Faculty of Medicine, Université Laval, Québec, QC, Canada
| | - Jean Ruel
- Centre de recherche en organogénèse expérimentale de l'Université Laval/LOEX, Division of Regenerative Medicine, CHU de Québec Research Centre - Université Laval, Québec, QC, Canada; Department of Mechanical Engineering, Faculty of Science and Engineering, Université Laval, Québec, QC, Canada
| | - Lucie Germain
- Centre de recherche en organogénèse expérimentale de l'Université Laval/LOEX, Division of Regenerative Medicine, CHU de Québec Research Centre - Université Laval, Québec, QC, Canada; Department of Surgery, Faculty of Medicine, Université Laval, Québec, QC, Canada
| | - Julie Fradette
- Centre de recherche en organogénèse expérimentale de l'Université Laval/LOEX, Division of Regenerative Medicine, CHU de Québec Research Centre - Université Laval, Québec, QC, Canada; Department of Surgery, Faculty of Medicine, Université Laval, Québec, QC, Canada
| | - François A Auger
- Centre de recherche en organogénèse expérimentale de l'Université Laval/LOEX, Division of Regenerative Medicine, CHU de Québec Research Centre - Université Laval, Québec, QC, Canada; Department of Surgery, Faculty of Medicine, Université Laval, Québec, QC, Canada.
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23
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Salemi S, Tremp M, Plock JA, Andersson KE, Gobet R, Sulser T, Eberli D. Differentiated adipose-derived stem cells for bladder bioengineering. Scand J Urol 2015; 49:407-14. [DOI: 10.3109/21681805.2015.1004642] [Citation(s) in RCA: 13] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/07/2023]
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Abstract
An ideal vascular substitute, especially in <6 mm diameter applications, is a major clinical essentiality in blood vessel replacement surgery. Blood vessels are structurally complex and functionally dynamic tissue, with minimal regeneration potential. These have composite extracellular matrix (ECM) and arrangement. The interplay between ECM components and tissue specific cells gives blood vessels their specialized functional attributes. The core of vascular tissue engineering and regeneration relies on the challenges in creating vascular conduits that match native vessels and adequately regenerate in vivo. Out of numerous vascular regeneration concerns, the relevance of ECM emphasizes much attention toward appropriate choice of scaffold material and further scaffold development strategies. The review is intended to be focused on the various approaches of scaffold materials currently in use in vascular regeneration and current state of the art. Scaffold of choice in vascular tissue engineering ranges from natural to synthetic, decellularized, and even scaffold free approach. The applicability of tubular scaffold for in vivo vascular regeneration is under active investigation. A patent conduit with an ample endothelial luminal layer that can regenerate in vivo remains an unanswered query in the field of small diameter vascular tissue engineering. Besides, scaffolds developed for vascular regeneration, should aim at providing functional substitutes for use in a regenerative approach from the laboratory bench to patient bedside.
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Affiliation(s)
- Neelima Thottappillil
- Division of Tissue Engineering and Regeneration Technologies, Biomedical Technology Wing, Sree Chitra Tirunal Institute for Medical Sciences and Technology, Kerala, India
| | - Prabha D Nair
- Division of Tissue Engineering and Regeneration Technologies, Biomedical Technology Wing, Sree Chitra Tirunal Institute for Medical Sciences and Technology, Kerala, India
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25
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Adipose-Derived Stem Cells for Therapeutic Applications. Regen Med 2015. [DOI: 10.1007/978-1-4471-6542-2_9] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/27/2022] Open
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26
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Arya D, Chang S, DiMuzio P, Carpenter J, Tulenko TN. Sphingosine-1-phosphate promotes the differentiation of adipose-derived stem cells into endothelial nitric oxide synthase (eNOS) expressing endothelial-like cells. J Biomed Sci 2014; 21:55. [PMID: 24898615 PMCID: PMC4064270 DOI: 10.1186/1423-0127-21-55] [Citation(s) in RCA: 16] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/05/2014] [Accepted: 05/15/2014] [Indexed: 03/02/2023] Open
Abstract
BACKGROUND Adipose tissue provides a readily available source of autologous stem cells. Adipose-derived stem cells (ASCs) have been proposed as a source for endothelial cell substitutes for lining the luminal surface of tissue engineered bypass grafts. Endothelial nitric oxide synthase (eNOS) is a key protein in endothelial cell function. Currently, endothelial differentiation from ASCs is limited by poor eNOS expression. The goal of this study was to investigate the role of three molecules, sphingosine-1-phosphate (S1P), bradykinin, and prostaglandin-E1 (PGE1) in ASC endothelial differentiation. Endothelial differentiation markers (CD31, vWF and eNOS) were used to evaluate the level of ASCs differentiation capability. RESULTS ASCs demonstrated differentiation capability toward to adipose, osteocyte and endothelial like cell phenotypes. Bradykinin, S1P and PGE were used to promote differentiation of ASCs to an endothelial phenotype. Real-time PCR showed that all three molecules induced significantly greater expression of endothelial differentiation markers CD31, vWF and eNOS than untreated cells. Among the three molecules, S1P showed the highest up-regulation on endothelial differentiation markers. Immunostaining confirmed presence of more eNOS in cells treated with S1P than the other groups. Cell growth measurements by MTT assay, cell counting and EdU DNA incorporation suggest that S1P promotes cell growth during ASCs endothelial differentiation. The S1P1 receptor was expressed in ASC-differentiated endothelial cells and S1P induced up-regulation of PI3K. CONCLUSIONS S1P up-regulates endothelial cell markers including eNOS in ASCs differentiated to endothelial like cells. This up-regulation appears to be mediated by the up-regulation of PI3K via S1P1 receptor. ASCs treated with S1P offer promising use as endothelial cell substitutes for tissue engineered vascular grafts and vascular networks.
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Affiliation(s)
| | | | | | | | - Thomas N Tulenko
- Department of Surgery, Cooper University Hospital and Cooper Medical School of Rowan University, 3 Cooper Plaza, Camden, NJ 08103, USA.
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27
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Boyette LB, Tuan RS. Adult Stem Cells and Diseases of Aging. J Clin Med 2014; 3:88-134. [PMID: 24757526 PMCID: PMC3992297 DOI: 10.3390/jcm3010088] [Citation(s) in RCA: 73] [Impact Index Per Article: 6.6] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/20/2013] [Revised: 12/15/2013] [Accepted: 12/17/2013] [Indexed: 02/06/2023] Open
Abstract
Preservation of adult stem cells pools is critical for maintaining tissue homeostasis into old age. Exhaustion of adult stem cell pools as a result of deranged metabolic signaling, premature senescence as a response to oncogenic insults to the somatic genome, and other causes contribute to tissue degeneration with age. Both progeria, an extreme example of early-onset aging, and heritable longevity have provided avenues to study regulation of the aging program and its impact on adult stem cell compartments. In this review, we discuss recent findings concerning the effects of aging on stem cells, contributions of stem cells to age-related pathologies, examples of signaling pathways at work in these processes, and lessons about cellular aging gleaned from the development and refinement of cellular reprogramming technologies. We highlight emerging therapeutic approaches to manipulation of key signaling pathways corrupting or exhausting adult stem cells, as well as other approaches targeted at maintaining robust stem cell pools to extend not only lifespan but healthspan.
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Affiliation(s)
- Lisa B Boyette
- Center for Cellular and Molecular Engineering, Department of Orthopaedic Surgery, University of Pittsburgh, Pittsburgh, PA 15219, USA; ; McGowan Institute for Regenerative Medicine, University of Pittsburgh, Pittsburgh, PA 15219, USA
| | - Rocky S Tuan
- Center for Cellular and Molecular Engineering, Department of Orthopaedic Surgery, University of Pittsburgh, Pittsburgh, PA 15219, USA; ; McGowan Institute for Regenerative Medicine, University of Pittsburgh, Pittsburgh, PA 15219, USA ; Department of Bioengineering, University of Pittsburgh, Pittsburgh, PA 15261, USA
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28
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Feng L, Wu H, E L, Wang D, Feng F, Dong Y, Liu H, Wang L. Effects of vascular endothelial growth factor 165 on bone tissue engineering. PLoS One 2013; 8:e82945. [PMID: 24376611 PMCID: PMC3869747 DOI: 10.1371/journal.pone.0082945] [Citation(s) in RCA: 15] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/06/2013] [Accepted: 11/06/2013] [Indexed: 12/31/2022] Open
Abstract
To study the relationship between vascular endothelial growth factor (VEGF) and formation and repair of engineering bone, second-generation bone marrow stromal cells (BMSCs) of New Zealand white rabbits that were separated in vitro were transfected with VEGF 165 gene vectors by adenovirus to detect gene expressions. Transfected BMSCs and β-tricalcium phosphate material were complexed and implanted at the femoral injury sites of the study group (n = 12), and the control group (n = 12) were implanted with engineering bones that were not transfected with VEGF. Femoral recoveries of the two groups were observed on the 15th, 30th, 45th and 60th days, and their vascularization and ossification statuses were observed by immunohistochemical methods. The BMSCs transfected with VEGF highly expressed VEGF genes and excreted VEGF. The two groups both experienced increased vascularization and bone volume after implantation (t = 7.92, P<0.05), and the increases of the study group were significantly higher than those of the control group (t = 6.92, P<0.05). VEGF is clinically applicable because it can accelerate the formation and repair of engineering bone by promoting vascularization and ossification.
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Affiliation(s)
- Lin Feng
- Oral Medical Research Center, Chinese PLA General Hospital, Beijing, P. R. China
- * E-mail:
| | - Hao Wu
- Oral Medical Research Center, Chinese PLA General Hospital, Beijing, P. R. China
| | - Lingling E
- Oral Medical Research Center, Chinese PLA General Hospital, Beijing, P. R. China
| | - Dongsheng Wang
- Oral Medical Research Center, Chinese PLA General Hospital, Beijing, P. R. China
| | - Fukui Feng
- Oral Medical Research Center, Chinese PLA General Hospital, Beijing, P. R. China
| | - Yuwan Dong
- Oral Medical Research Center, Chinese PLA General Hospital, Beijing, P. R. China
| | - Hongchen Liu
- Oral Medical Research Center, Chinese PLA General Hospital, Beijing, P. R. China
| | - Lili Wang
- Department of Prosthodontics, Affiliated Stomatological Hospital of LMU, Jinzhou, P. R. China
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Development of a new pre-vascularized tissue-engineered construct using pre-differentiated rADSCs, arteriovenous vascular bundle and porous nano-hydroxyapatide-polyamide 66 scaffold. BMC Musculoskelet Disord 2013; 14:318. [PMID: 24209783 PMCID: PMC3826526 DOI: 10.1186/1471-2474-14-318] [Citation(s) in RCA: 18] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/09/2013] [Accepted: 11/05/2013] [Indexed: 01/22/2023] Open
Abstract
Background Development of a pre-vascularized tissue-engineered construct with intrinsic vascular system for cell growth and tissue formation still faces many difficulties due to the complexity of the vascular network of natural bone tissue. The present study was to design and form a new vascularized tissue-engineered construct using pre-differentiated rADSCs, arteriovenous vascular bundle and porous nHA-PA 66 scaffold. Methods rADSCs were pre-differentiated to endothelial cells (rADSCs-Endo) and then incorporated in nHA-PA 66 scaffolds in vitro. Subsequently, in vivo experiments were carried out according to the following groups: Group A (rADSCs-Endo/nHA-PA 66 scaffold with arteriovenous vascular bundle), Group B (rADSCs/nHA-PA 66 scaffold with arteriovenous vascular bundle); Group C (nHA-PA66 scaffold with arteriovenous vascular bundle), Group D (nHA-PA 66 scaffold only). The vessel density and vessel diameter were measured based on histological and immunohistochemical evaluation, furthermore, the VEGF-C, FGF-2 and BMP-2 protein expressions were also evaluated by western blot analysis. Results The results of in vivo experiments showed that the vessel density and vessel diameter in group A were significantly higher than the other three groups. Between Group B and C, no statistical difference was observed at each time point. In accordance with the results, there were dramatically higher expressions of VEGF-C and FGF-2 protein in Group A than that of Group B, C and D at 2 or 4 weeks. Statistical differences were not observed in VEGF-C and FGF-2 expression between Group B and C. BMP-2 was not expressed in any group at each time point. Conclusions Compared with muscular wrapping method, arteriovenous vascular bundle implantation could promote vascularization of the scaffold; and the angiogenesis of the scaffold was significantly accelerated when pre-differentiated rADSCs (endothelial differentiation) were added. These positive results implicate the combination of pre-differentiated rADSCs (endothelial differentiation) and arteriovenous vascular bundle may achieve rapidly angiogenesis of biomaterial scaffold.
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Sharma RR, Pollock K, Hubel A, McKenna D. Mesenchymal stem or stromal cells: a review of clinical applications and manufacturing practices. Transfusion 2013; 54:1418-37. [PMID: 24898458 DOI: 10.1111/trf.12421] [Citation(s) in RCA: 307] [Impact Index Per Article: 25.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/01/2013] [Revised: 08/05/2013] [Accepted: 08/09/2013] [Indexed: 12/11/2022]
Abstract
Mesenchymal stem cells (MSCs) have recently generated great interest in the fields of regenerative medicine and immunotherapy due to their unique biologic properties. In this review we attempt to provide an overview of the current clinical status of MSC therapy, primarily focusing on immunomodulatory and regenerative or tissue repair applications of MSCs. In addition, current manufacturing is reviewed with attention to variation in practices (e.g., starting material, approach to culture and product testing). There is considerable variation among the 218 clinical trials assessed here; variations include proposed mechanisms of action, optimal dosing strategy, and route of administration. To ensure the greatest likelihood of success in clinical trials as the field progresses, attention must be given to the optimization of MSC culture.
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Affiliation(s)
- Ratti Ram Sharma
- Department of Transfusion Medicine, Post graduate Institute of Medical Education and Research, Chandīgarh, India
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Rajangam T, An SSA. Fibrinogen and fibrin based micro and nano scaffolds incorporated with drugs, proteins, cells and genes for therapeutic biomedical applications. Int J Nanomedicine 2013; 8:3641-62. [PMID: 24106425 PMCID: PMC3792008 DOI: 10.2147/ijn.s43945] [Citation(s) in RCA: 53] [Impact Index Per Article: 4.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/24/2022] Open
Abstract
Over the past two decades, many types of natural and synthetic polymer-based micro- and nanocarriers, with exciting properties and applications, have been developed for application in various types of tissue regeneration, including bone, cartilage, nerve, blood vessels, and skin. The development of suitable polymers scaffold designs to aid the repair of specific cell types have created diverse and important potentials in tissue restoration. Fibrinogen (Fbg)- and fibrin (Fbn)-based micro- and nanostructures can provide suitable natural matrix environments. Since these primary materials are abundantly available in blood as the main coagulation proteins, they can easily interact with damaged tissues and cells through native biochemical interactions. Fbg- and Fbn-based micro and nanostructures can also be consecutively furnished/or encapsulated and specifically delivered, with multiple growth factors, proteins, and stem cells, in structures designed to aid in specific phases of the tissue regeneration process. The present review has been carried out to demonstrate the progress made with micro and nanoscaffold applications and features a number of applications of Fbg- and Fbn-based carriers in the field of biomaterials, including the delivery of drugs, active biomolecules, cells, and genes, that have been effectively used in tissue engineering and regenerative medicine.
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Affiliation(s)
- Thanavel Rajangam
- Department of Bionanotechnology, Gachon University, Seongnam-Si, Republic of Korea
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Pikuła M, Marek-Trzonkowska N, Wardowska A, Renkielska A, Trzonkowski P. Adipose tissue-derived stem cells in clinical applications. Expert Opin Biol Ther 2013; 13:1357-70. [PMID: 23919743 DOI: 10.1517/14712598.2013.823153] [Citation(s) in RCA: 63] [Impact Index Per Article: 5.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/15/2022]
Abstract
INTRODUCTION In the past decade human adipose tissue has been identified as a source of multipotent stem cells. Adipose tissue derived stem cells (ASCs) are characterised by immunosuppressive properties and low immunogenicity. Therefore, they can be used in regenerative medicine, as well as applied to induce graft tolerance or prevent autoimmunity. ASCs can be easily harvested with low morbidity, which is their main advantage over mesenchymal stem cells (MSCs) derived from other sources. AREAS COVERED The review focuses on reported clinical applications of ASCs and discusses technical approaches of their isolation and processing. The differences in phenotype and differentiation preferences between ASCs and other MSCs that may affect the choice of a particular cell type for the future therapy are also described. EXPERT OPINION ASCs seem to be the perfect tool for regenerative medicine and immunosuppressive cellular therapies. Nevertheless, there are some tasks that should be addressed by the future studies: i) ASCs require better characterisation; a set of markers determining ASCs should be clearly defined; ii) there is need for more studies on safety of reconstructive therapies with ASCs in cancer patients (e.g., after mastectomy); iii) release criteria should be determined for freshly isolated and ex vivo expanded ASCs designed for clinical applications.
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Affiliation(s)
- Michał Pikuła
- Medical University of Gdańsk, Department of Clinical Immunology and Transplantology , ul. Dębinki 7, 80-210 Gdańsk , Poland
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Abstract
It is well known that the altered blood flow is related to vascular diseases, including atherosclerosis, restenosis, and arteriosclerosis, which preferentially located at areas with the disturbed blood flow, suggesting that altered biomechanical stress may exert their effect on the vascular disease. Recent evidence indicated the presence of abundant stem/progenitor cells in the vessel wall, in which laminar shear stress can stimulate these cells to differentiate towards endothelial lineage, while cyclic strain results in smooth muscle differentiation. In line with this, it was evidenced that altered biomechanical stress in stented vessels may lead to 'wrong' direction of vascular stem cell differentiation resulting in restenosis. However, the underlying mechanisms are not well understood. In this article, we will give an overview of the effect of the local flow pattern on stem/progenitor cell differentiation and the possible mechanism on how the blood flow influences stem cell behaviours in the development of vascular diseases.
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Affiliation(s)
- Cheng Zhang
- The Key Laboratory of Cardiovascular Remodeling and Function Research, Chinese Ministry of Education and Chinese Ministry of Health, Shandong University Qilu Hospital, Jinan, China
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Chua KH, Raduan F, Wan Safwani WKZ, Manzor NFM, Pingguan-Murphy B, Sathapan S. Effects of serum reduction and VEGF supplementation on angiogenic potential of human adipose stromal cells in vitro. Cell Prolif 2013; 46:300-11. [PMID: 23672290 DOI: 10.1111/cpr.12029] [Citation(s) in RCA: 14] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/19/2012] [Accepted: 12/24/2012] [Indexed: 12/12/2022] Open
Abstract
OBJECTIVES This study investigated effects of reduced serum condition and vascular endothelial growth factor (VEGF) on angiogenic potential of adipose stromal cells (ASCs) in vitro. MATERIALS AND METHODS Adipose stromal cells were cultured in three different types of medium: (i) F12/DMEM (FD) supplemented with 10% FBS from passage 0 (P0) to P6; (ii) FD supplemented with 2% FBS at P6; and (iii) FD supplemented with 2% FBS plus 50 ng/ml of VEGF at P6. Morphological changes and growth rate of ASCs were recorded. Changes in stemness, angiogenic and endogenic genes' expressions were analysed using Real-Time PCR. RESULTS Adipose stromal cells changed from fibroblast-like shape when cultured in 10% FBS medium to polygonal when cultured in 2% FBS plus VEGF-supplemented medium. Their growth rate was lower in 2% FBS medium, but increased with addition of VEGF. Real-Time PCR showed that ASCs maintained most of their stemness and angiogenic genes' expression in 10% FBS at P1, P5 and P6, but this increased significantly in 2% FBS at P6. Endogenic genes expression such as PECAM-1, VE chaderin and VEGFR-2 decreased after serial passage in 10% FBS, but increased significantly at P6 in 2% FBS. Addition of VEGF did not cause any significant change in gene expression level. CONCLUSION Adipose stromal cells had greater angiogenic potential when cultured in reduced serum conditions. VEGF did not enhance their angiogenic potential in 2% FBS-supplemented medium.
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Affiliation(s)
- K H Chua
- Department of Physiology, Faculty of Medicine, Universiti Kebangsaan Malaysia, Kuala Lumpur 50300, Malaysia.
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Shi Z, Neoh KG, Kang ET. In vitro endothelialization of cobalt chromium alloys with micro/nanostructures using adipose-derived stem cells. JOURNAL OF MATERIALS SCIENCE. MATERIALS IN MEDICINE 2013; 24:1067-1077. [PMID: 23371765 DOI: 10.1007/s10856-013-4868-7] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 08/31/2012] [Accepted: 01/18/2013] [Indexed: 06/01/2023]
Abstract
In this study, integrin expression, proliferation, and endothelial differentiation of adipose-derived stem cells (ADSCs) on pristine cobalt chrome (CoCr) surface, microstructured and nanostructured CoCr surfaces (obtained after treatment with piranha solution) were investigated. The results showed that proliferation of ADSCs on the substrates treated with piranha solution is not significantly different from that on the pristine substrates. However, quantitative real-time PCR analysis showed significantly enhanced up-regulation of CD31, vWF and eNOS from gene level by ADSCs on the nanostructured substrates but not on the microstructured substrates. The adsorption of vitronectin from the culture medium on the nanostructured substrates was higher than on the pristine and microstructured substrates. We speculate that this results in increased integrin αvβ3 expression in the ADSCs, which may contribute partially to the enhanced endothelial differentiation of ADSCs on the nanostructured substrates. This study shows that ADSCs can be used to endothelialize stents in vitro and the endothelial differentiation of ADSC is enhanced on the nanostructured surfaces.
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Affiliation(s)
- Zhilong Shi
- Department of Chemical and Biomolecular Engineering, National University of Singapore, Kent Ridge, Singapore, Singapore
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Abstract
In 2001, researchers at the University of California, Los Angeles, described the isolation of a new population of adult stem cells from liposuctioned adipose tissue. These stem cells, now known as adipose-derived stem cells or ADSCs, have gone on to become one of the most popular adult stem cells populations in the fields of stem cell research and regenerative medicine. As of today, thousands of research and clinical articles have been published using ASCs, describing their possible pluripotency in vitro, their uses in regenerative animal models, and their application to the clinic. This paper outlines the progress made in the ASC field since their initial description in 2001, describing their mesodermal, ectodermal, and endodermal potentials both in vitro and in vivo, their use in mediating inflammation and vascularization during tissue regeneration, and their potential for reprogramming into induced pluripotent cells.
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Porzionato A, Sfriso MM, Macchi V, Rambaldo A, Lago G, Lancerotto L, Vindigni V, De Caro R. Decellularized omentum as novel biologic scaffold for reconstructive surgery and regenerative medicine. Eur J Histochem 2013; 57:e4. [PMID: 23549463 PMCID: PMC3683611 DOI: 10.4081/ejh.2013.e4] [Citation(s) in RCA: 44] [Impact Index Per Article: 3.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/09/2012] [Revised: 09/17/2012] [Accepted: 09/19/2012] [Indexed: 12/17/2022] Open
Abstract
Homologous tissues, such as adipose tissue, may be an interesting source of acellular scaffolds, maintaining a complex physiological three-dimensional (3D) structure, to be recellularized with autologous cells. The aim of the present work is to evaluate the possibility of obtaining homologous acellular scaffolds from decellularization of the omentum, which is known to have a complex vascular network. Adult rat and human omenta were treated with an adapted decellularization protocol involving mechanical rupture (freeze-thaw cycles), enzymatic digestion (trypsin, lipase, deoxyribonuclease, ribonuclease) and lipid extraction (2-propanol). Histological staining confirmed the effectiveness of decellularization, resulting in cell-free scaffolds with no residual cells in the matrix. The complex 3D networks of collagen (azan-Mallory), elastic fibers (Van Gieson), reticular fibers and glycosaminoglycans (PAS) were maintained, whereas Oil Red and Sudan stains showed the loss of lipids in the decellularized tissue. The vascular structures in the tissue were still visible, with preservation of collagen and elastic wall components and loss of endothelial (anti-CD31 and -CD34 immunohistochemistry) and smooth muscle (anti-alpha smooth muscle actin) cells. Fat-rich and well vascularized omental tissue may be decellularized to obtain complex 3D scaffolds preserving tissue architecture potentially suitable for recellularization. Further analyses are necessary to verify the possibility of recolonization of the scaffold by adipose-derived stem cells in vitro and then in vivo after re implantation, as already known for homologus implants in regenerative processes.
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Affiliation(s)
- A Porzionato
- Section of Human Anatomy, Department of Molecular Medicine, University of Padua, Padova,
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McIlhenny S, Zhang P, Tulenko T, Comeau J, Fernandez S, Policha A, Ferroni M, Faul E, Bagameri G, Shapiro I, DiMuzio P. eNOS transfection of adipose-derived stem cells yields bioactive nitric oxide production and improved results in vascular tissue engineering. J Tissue Eng Regen Med 2013; 9:1277-85. [PMID: 23319464 DOI: 10.1002/term.1645] [Citation(s) in RCA: 26] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/09/2012] [Revised: 07/19/2012] [Accepted: 10/04/2012] [Indexed: 11/10/2022]
Abstract
This study evaluates the durability of a novel tissue engineered blood vessel (TEBV) created by seeding a natural vascular tissue scaffold (decellularized human saphenous vein allograft) with autologous adipose-derived stem cells (ASC) differentiated into endothelial-like cells. Previous work with this model revealed the graft to be thrombogenic, likely due to inadequate endothelial differentiation as evidenced by minimal production of nitric oxide (NO). To evaluate the importance of NO expression by the seeded cells, we created TEBV using autologous ASC transfected with the endothelial nitric oxide synthase (eNOS) gene to produce NO. We found that transfected ASC produced NO at levels similar to endothelial cell (EC) controls in vitro which was capable of causing vasorelaxation of aortic specimens ex vivo. TEBV (n = 5) created with NO-producing ASC and implanted as interposition grafts within the aorta of rabbits remained patent for two months and demonstrated a non-thrombogenic surface compared to unseeded controls (n = 5). Despite the xenograft nature of the scaffold, the TEBV structure remained well preserved in seeded grafts. In sum, this study demonstrates that upregulation of NO expression within adult stem cells differentiated towards an endothelial-like lineage imparts a non-thrombogenic phenotype and highlights the importance of NO production by cells to be used as endothelial cell substitutes in vascular tissue engineering applications.
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Affiliation(s)
- Stephen McIlhenny
- Department of Surgery, Thomas Jefferson University, Philadelphia, PA, USA
| | - Ping Zhang
- Department of Surgery, Thomas Jefferson University, Philadelphia, PA, USA
| | - Thomas Tulenko
- Department of Surgery, Thomas Jefferson University, Philadelphia, PA, USA
| | - Jason Comeau
- Department of Surgery, Thomas Jefferson University, Philadelphia, PA, USA
| | - Sarah Fernandez
- Department of Surgery, Thomas Jefferson University, Philadelphia, PA, USA
| | - Aleksandra Policha
- Department of Surgery, Thomas Jefferson University, Philadelphia, PA, USA
| | - Matthew Ferroni
- Department of Surgery, Thomas Jefferson University, Philadelphia, PA, USA
| | - Elizabeth Faul
- Department of Orthopaedic Research, Thomas Jefferson University, Philadelphia, PA, USA
| | - Gabor Bagameri
- Department of Surgery, Thomas Jefferson University, Philadelphia, PA, USA
| | - Irving Shapiro
- Department of Orthopaedic Research, Thomas Jefferson University, Philadelphia, PA, USA
| | - Paul DiMuzio
- Department of Surgery, Thomas Jefferson University, Philadelphia, PA, USA
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Zuttion MSSR, Wenceslau CV, Lemos PA, Takimura C, Kerkis I. Adipose Tissue-Derived Stem Cells and the Importance of Animal Model Standardization for Pre-Clinical Trials. ACTA ACUST UNITED AC 2013. [DOI: 10.1016/s2214-1235(15)30145-9] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/14/2023]
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Current concepts and advances in the application of tissue engineering in otorhinolaryngology and head and neck surgery. J Laryngol Otol 2012; 127:114-20. [PMID: 23218135 DOI: 10.1017/s0022215112002642] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/07/2022]
Abstract
OBJECTIVE This paper reviews the progress in the rapidly expanding scientific discipline of tissue engineering, which may have an integral role in the future of otorhinolaryngology. This article seeks to inform on the current concepts and principles of tissue engineering, and describe the state of the art research and developments in this exciting field as applied to ENT and head and neck surgery. METHOD In order to carry out a comprehensive review of the literature spanning the past 30 years, a search of relevant publications was performed using the Web of Knowledge, Medline and PubMed databases. RESULTS This search identified 85 scholarly articles, which were utilised as the basis of this review. CONCLUSION Given the current rate of development of tissue engineering research, it is likely that tissue-engineered implants will be widely used in surgical practice, including ENT and head and neck surgery.
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Shi Z, Neoh KG, Kang ET, Poh CK, Wang W. Enhanced endothelial differentiation of adipose-derived stem cells by substrate nanotopography. J Tissue Eng Regen Med 2012; 8:50-8. [PMID: 22628362 DOI: 10.1002/term.1496] [Citation(s) in RCA: 37] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/24/2011] [Revised: 09/01/2011] [Accepted: 01/24/2012] [Indexed: 12/13/2022]
Abstract
Adipose-derived stem cells (ADSCs) have great potential as a cell source for tissue engineering and regenerative medicine because they are easier to obtain, have lower donor-site morbidity and are available in larger numbers than stem cells harvested using bone marrow aspiration. Until now, little has been known about how nanotopography affects the proliferation and endothelial differentiation of ADSCs. In the present study, two nanograting substrates with a period (ridge and groove) of about 250 and 500 nm, respectively, were fabricated on quartz and their effect on ADSC fate was investigated. The results showed that proliferation of ADSCs on nanograting substrates decreased while cell attachment was not significantly affected compared to a flat substrate. Endothelial differentiation of ADSCs on both flat and nanograting substrates can be induced with vascular endothelial growth factor, as shown by immunofluorescent staining. Quantitative real-time PCR analysis showed significantly enhanced upregulation of vWF, PECAM-1 and VE-cadherin at the gene level by ADSCs on the nanograting substrates. In vitro angiogenesis assay on Matrigel showed that nanograting substrates enhanced capillary tube formation. This study highlights the beneficial influence of nanotopography on the differentiation of ADSC into endothelial cells which play an important role in vascularization.
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Affiliation(s)
- Zhilong Shi
- Department of Chemical and Biomolecular Engineering, National University of Singapore
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Park IS, Kim SH, Heo DN, Jung Y, Kwon IK, Rhie JW, Kim SH. Synergistic Effect of Biochemical Factors and Strain on the Smooth Muscle Cell Differentiation of Adipose-Derived Stem Cells on an Elastic Nanofibrous Scaffold. JOURNAL OF BIOMATERIALS SCIENCE-POLYMER EDITION 2012; 23:1579-93. [DOI: 10.1163/092050611x587538] [Citation(s) in RCA: 9] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 11/19/2022]
Affiliation(s)
- In Su Park
- a Center for Biomaterials, Medical Engineering Institute, Korea Institute of Science and Technology , 39-1 Hawolgok, Seongbuk , Seoul , 136-791 , South Korea
| | - Soo Hyun Kim
- a Center for Biomaterials, Medical Engineering Institute, Korea Institute of Science and Technology , 39-1 Hawolgok, Seongbuk , Seoul , 136-791 , South Korea
| | - Dong Nyoung Heo
- b Department of Oral Biology , School of Dentistry, Kyung Hee University , Seoul , 130-701 , South Korea
| | - Youngmee Jung
- a Center for Biomaterials, Medical Engineering Institute, Korea Institute of Science and Technology , 39-1 Hawolgok, Seongbuk , Seoul , 136-791 , South Korea
| | - Il Keun Kwon
- b Department of Oral Biology , School of Dentistry, Kyung Hee University , Seoul , 130-701 , South Korea
| | - Jong-Won Rhie
- c Department of Plastic Surgery , College of Medicine, The Catholic University of Korea , Seoul , 137-701 , South Korea
| | - Sang-Heon Kim
- a Center for Biomaterials, Medical Engineering Institute, Korea Institute of Science and Technology , 39-1 Hawolgok, Seongbuk , Seoul , 136-791 , South Korea
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Krawiec JT, Vorp DA. Adult stem cell-based tissue engineered blood vessels: A review. Biomaterials 2012; 33:3388-400. [DOI: 10.1016/j.biomaterials.2012.01.014] [Citation(s) in RCA: 89] [Impact Index Per Article: 6.8] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/14/2011] [Accepted: 01/05/2012] [Indexed: 12/20/2022]
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Szpalski C, Barbaro M, Sagebin F, Warren SM. Bone tissue engineering: current strategies and techniques--part II: Cell types. TISSUE ENGINEERING PART B-REVIEWS 2012; 18:258-69. [PMID: 22224439 DOI: 10.1089/ten.teb.2011.0440] [Citation(s) in RCA: 69] [Impact Index Per Article: 5.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 12/17/2022]
Abstract
Bone repair and regeneration is a dynamic process that involves a complex interplay between the (1) ground substance; (2) cells; and (3) milieu. Each constituent is integral to the final product, but it is often helpful to consider each component individually. While bone tissue engineering has capitalized on a number of breakthrough technologies, one of the most valued advancements is the incorporation of mesenchymal stem cells (SCs) into bone tissue engineering applications. With this new idea, however, came new found problems of guiding SC differentiation. Moreover, investigators are still working to understand which SCs source produces optimal bone formation in vitro and in vivo. Bone marrow-derived mesenchymal SCs and adipose-derived SCs have been researched most extensively, but other SC sources, including dental pulp, blood, umbilical cord blood, epithelial cells reprogrammed to become induced pluripotent SCs, among others, are being investigated. In Part II of this review series, we discuss the variety of cell types (e.g., osteocytes, osteoblasts, osteoclasts, chondrocytes, mesenchymal SCs, and vasculogenic cells) important in bone tissue engineering.
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Affiliation(s)
- Caroline Szpalski
- Department of Plastic Surgery, New York University Langone Medical Center, New York, New York 10016, USA
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Rathore A, Cleary M, Naito Y, Rocco K, Breuer C. Development of tissue engineered vascular grafts and application of nanomedicine. WILEY INTERDISCIPLINARY REVIEWS-NANOMEDICINE AND NANOBIOTECHNOLOGY 2012; 4:257-72. [DOI: 10.1002/wnan.1166] [Citation(s) in RCA: 34] [Impact Index Per Article: 2.6] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/22/2023]
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Zhang H, Albersen M, Jin X, Lin G. Stem cells: novel players in the treatment of erectile dysfunction. Asian J Androl 2012; 14:145-55. [PMID: 22002437 PMCID: PMC3735142 DOI: 10.1038/aja.2011.79] [Citation(s) in RCA: 33] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/04/2011] [Revised: 06/30/2011] [Accepted: 07/19/2011] [Indexed: 01/09/2023] Open
Abstract
Stem cells are defined by their capacity for both self-renewal and directed differentiation; thus, they represent great promise for regenerative medicine. Historically, stem cells have been categorized as either embryonic stem cells (ESCs) or adult stem cells (ASCs). It was previously believed that only ESCs hold the ability to differentiate into any cell type, whereas ASCs have the capacity to give rise only to cells of a given germ layer. More recently, however, numerous studies demonstrated the ability of ASCs to differentiate into cell types beyond their tissue origin. The aim of this review was to summarize contemporary evidence regarding stem cell availability, differentiation, and more specifically, the potential of these cells in the diagnosis and treatment of erectile dysfunction (ED) in both animal models and human research. We performed a search on PubMed for articles related to definition, localisation and circulation of stem cells as well as the application of stem cells in both diagnosis and treatment of ED. Strong evidence supports the concept that stem cell therapy is potentially the next therapeutic approach for ED. To date, a large spectrum of stem cells, including bone marrow mesenchymal stem cells, adipose tissue-derived stem cells and muscle-derived stem cells, have been investigated for neural, vascular, endothelial or smooth muscle regeneration in animal models for ED. In addition, several subtypes of ASCs are localized in the penis, and circulating endogenous stem cells can be employed to predict the outcome of ED and ED-related cardiovascular diseases.
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Affiliation(s)
- Haiyang Zhang
- Minimally Invasive Urology Center, Provincial Hospital Affiliated to Shandong University, Jinan, China
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Sundaram S, Niklason LE. Smooth muscle and other cell sources for human blood vessel engineering. Cells Tissues Organs 2011; 195:15-25. [PMID: 22041291 DOI: 10.1159/000331409] [Citation(s) in RCA: 27] [Impact Index Per Article: 1.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/09/2023] Open
Abstract
Despite substantial progress in the field of vascular tissue engineering over the past decades, transition to human models has been rather challenging. The limited replicative life spans of human adult vascular cells, and their slow rate of collagenous matrix production in vitro, have posed important hurdles in the development of mechanically robust and biologically functional engineered grafts. With the more recent advances in the field of stem cells, investigators now have access to a plethora of new cell source alternatives for vascular engineering. In this paper, we review various alternative cell sources made available more recently for blood vessel engineering and also present some recent data on the derivation of smooth muscle cells from human induced pluripotent stem cells.
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Affiliation(s)
- Sumati Sundaram
- Department of Biomedical Engineering, Yale University, New Haven, Conn., USA
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Harris LJ, Abdollahi H, Zhang P, McIlhenny S, Tulenko TN, DiMuzio PJ. Differentiation of adult stem cells into smooth muscle for vascular tissue engineering. J Surg Res 2011; 168:306-14. [PMID: 19959190 PMCID: PMC2888621 DOI: 10.1016/j.jss.2009.08.001] [Citation(s) in RCA: 74] [Impact Index Per Article: 5.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/18/2009] [Revised: 07/24/2009] [Accepted: 08/04/2009] [Indexed: 11/18/2022]
Abstract
BACKGROUND Herein we evaluate the potential of adipose-derived stem cells (ASC) to differentiate into smooth muscle cells (SMC) and their potential for use in a tissue-engineered vascular graft. MATERIALS AND METHODS We isolated ASC (CD13+29+90+) from the peri-umbilical adipose tissue of patients undergoing vascular surgery, and cultured them in media containing angiotensin II (AngII), sphingosylphosphorylcholine (SPC), or transforming growth factor-beta 1 (TGFβ1) for up to 3 weeks. SMC differentiation was assessed by (1) expression of early (calponin, caldesmon) and late (myosin heavy chain, MHC) SMC markers by RT-PCR, qPCR and Western blot, and (2) contraction upon plating on collagen gel. Differentiated ASCs were seeded onto a vascular graft (decellularized saphenous vein) within a bioreactor, and cell attachment was determined using confocal microscopy. RESULTS Prior to differentiation, ASC expressed low levels of all three molecular markers. After culture in each differentiating medium, the extent of up-regulation of calponin, caldesmon, and MHC was variable across all cell lines. After seeding onto collagen gel, ASCs differentiated in SPC and TGFβ1 exhibit contractile properties, similar to smooth muscle cell controls. Differentiated stem cells adhered and proliferated on the vascular graft. CONCLUSION These data suggest that human adipose-derived stem cells (1) exhibit variable expression of SMC molecular markers after differentiation, (2) exhibit a contractile phenotype after differentiation with SPC and TGFβ1, and (3) proliferate on a vascular graft scaffold. Thus, ASCs are potentially useful in the construction of autologous arteries.
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Affiliation(s)
- Lisa J Harris
- Department of Surgery, Thomas Jefferson University, Philadelphia, Pennsylvania 19107, USA
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Liu K, Liu R, Cao G, Sun H, Wang X, Wu S. Adipose-Derived Stromal Cell Autologous Transplantation Ameliorates Pulmonary Arterial Hypertension Induced by Shunt Flow in Rat Models. Stem Cells Dev 2011; 20:1001-10. [DOI: 10.1089/scd.2010.0222] [Citation(s) in RCA: 29] [Impact Index Per Article: 2.1] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/18/2022] Open
Affiliation(s)
- Kai Liu
- The Key Laboratory of Cardiovascular Remodeling and Function Research, Chinese Ministry of Education and Chinese Ministry of Health, Division of Medicine, Department of Cardiovascular Surgery, Qilu Hospital of Shandong University, Jinan, People's Republic of China
| | - Ruifang Liu
- The Key Laboratory of Cardiovascular Remodeling and Function Research, Chinese Ministry of Education and Chinese Ministry of Health, Division of Medicine, Department of Cardiovascular Surgery, Qilu Hospital of Shandong University, Jinan, People's Republic of China
| | - Guangqing Cao
- The Key Laboratory of Cardiovascular Remodeling and Function Research, Chinese Ministry of Education and Chinese Ministry of Health, Division of Medicine, Department of Cardiovascular Surgery, Qilu Hospital of Shandong University, Jinan, People's Republic of China
| | - Hourong Sun
- The Key Laboratory of Cardiovascular Remodeling and Function Research, Chinese Ministry of Education and Chinese Ministry of Health, Division of Medicine, Department of Cardiovascular Surgery, Qilu Hospital of Shandong University, Jinan, People's Republic of China
| | - Xuping Wang
- The Key Laboratory of Cardiovascular Remodeling and Function Research, Chinese Ministry of Education and Chinese Ministry of Health, Division of Medicine, Department of Cardiovascular Surgery, Qilu Hospital of Shandong University, Jinan, People's Republic of China
| | - Shuming Wu
- The Key Laboratory of Cardiovascular Remodeling and Function Research, Chinese Ministry of Education and Chinese Ministry of Health, Division of Medicine, Department of Cardiovascular Surgery, Qilu Hospital of Shandong University, Jinan, People's Republic of China
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