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Olate-Moya F, Rubí-Sans G, Engel E, Mateos-Timoneda MÁ, Palza H. 3D Bioprinting of Biomimetic Alginate/Gelatin/Chondroitin Sulfate Hydrogel Nanocomposites for Intrinsically Chondrogenic Differentiation of Human Mesenchymal Stem Cells. Biomacromolecules 2024; 25:3312-3324. [PMID: 38728671 DOI: 10.1021/acs.biomac.3c01444] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 05/12/2024]
Abstract
3D-printed hydrogel scaffolds biomimicking the extracellular matrix (ECM) are key in cartilage tissue engineering as they can enhance the chondrogenic differentiation of mesenchymal stem cells (MSCs) through the presence of active nanoparticles such as graphene oxide (GO). Here, biomimetic hydrogels were developed by cross-linking alginate, gelatin, and chondroitin sulfate biopolymers in the presence of GO as a bioactive filler, with excellent processability for developing bioactive 3D printed scaffolds and for the bioprinting process. A novel bioink based on our hydrogel with embedded human MSCs presented a cell survival rate near 100% after the 3D bioprinting process. The effects of processing and filler concentration on cell differentiation were further quantitatively evaluated. The nanocomposited hydrogels render high MSC proliferation and viability, exhibiting intrinsic chondroinductive capacity without any exogenous factor when used to print scaffolds or bioprint constructs. The bioactivity depended on the GO concentration, with the best performance at 0.1 mg mL-1. These results were explained by the rational combination of the three biopolymers, with GO nanoparticles having carboxylate and sulfate groups in their structures, therefore, biomimicking the highly negatively charged ECM of cartilage. The bioactivity of this biomaterial and its good processability for 3D printing scaffolds and 3D bioprinting techniques open up a new approach to developing novel biomimetic materials for cartilage repair.
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Affiliation(s)
- Felipe Olate-Moya
- Departamento de Ingeniería Química, Biotecnología y Materiales, Facultad de Ciencias Físicas y Matemáticas, Universidad de Chile, Avenida Beauchef 851, 8370458 Santiago, Chile
- IMPACT, Center of Interventional Medicine for Precision and Advanced Cellular Therapy, Avenida Monseñor Álvaro del Portillo 12455, 7620086 Las Condes, Chile
| | - Gerard Rubí-Sans
- Institute for Bioengineering of Catalonia (IBEC), The Barcelona Institute of Science and Technology (BIST), Carrer de Baldiri Reixac, 10, 12, 08028, 08019 Barcelona, Spain
- CIBER en Bioingeniería, Biomateriales y Nanomedicina, CIBER-BBN, 50018 Zaragoza, Spain
| | - Elisabeth Engel
- IMEM-BRT Group, Departament de Ciència i Enginyeria de Materials, EEBE, Universitat Politècnica de Catalunya (UPC), C/Eduard Maristany 10-14, 08019 Barcelona, Spain
- Institute for Bioengineering of Catalonia (IBEC), The Barcelona Institute of Science and Technology (BIST), Carrer de Baldiri Reixac, 10, 12, 08028, 08019 Barcelona, Spain
- CIBER en Bioingeniería, Biomateriales y Nanomedicina, CIBER-BBN, 50018 Zaragoza, Spain
| | - Miguel Ángel Mateos-Timoneda
- Bioengineering Institute of Technology, Universitat Internacional de Catalunya, Josep Trueta Street s/n, 08195 Sant Cugat del Vallès, Barcelona, Spain
- Department of Basic Sciences, Faculty of Medicine and Health Sciences, Univesitat Internacional de Catalunya, Josep Trueta Street s/n, 08195 Sant Cugat del Vallès, Barcelona, Spain
| | - Humberto Palza
- Departamento de Ingeniería Química, Biotecnología y Materiales, Facultad de Ciencias Físicas y Matemáticas, Universidad de Chile, Avenida Beauchef 851, 8370458 Santiago, Chile
- IMPACT, Center of Interventional Medicine for Precision and Advanced Cellular Therapy, Avenida Monseñor Álvaro del Portillo 12455, 7620086 Las Condes, Chile
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Ohnishi T, Homan K, Fukushima A, Ukeba D, Iwasaki N, Sudo H. A Review: Methodologies to Promote the Differentiation of Mesenchymal Stem Cells for the Regeneration of Intervertebral Disc Cells Following Intervertebral Disc Degeneration. Cells 2023; 12:2161. [PMID: 37681893 PMCID: PMC10486900 DOI: 10.3390/cells12172161] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/30/2023] [Revised: 08/24/2023] [Accepted: 08/26/2023] [Indexed: 09/09/2023] Open
Abstract
Intervertebral disc (IVD) degeneration (IDD), a highly prevalent pathological condition worldwide, is widely associated with back pain. Treatments available compensate for the impaired function of the degenerated IVD but typically have incomplete resolutions because of their adverse complications. Therefore, fundamental regenerative treatments need exploration. Mesenchymal stem cell (MSC) therapy has been recognized as a mainstream research objective by the World Health Organization and was consequently studied by various research groups. Implanted MSCs exert anti-inflammatory, anti-apoptotic, and anti-pyroptotic effects and promote extracellular component production, as well as differentiation into IVD cells themselves. Hence, the ultimate goal of MSC therapy is to recover IVD cells and consequently regenerate the extracellular matrix of degenerated IVDs. Notably, in addition to MSC implantation, healthy nucleus pulposus (NP) cells (NPCs) have been implanted to regenerate NP, which is currently undergoing clinical trials. NPC-derived exosomes have been investigated for their ability to differentiate MSCs from NPC-like phenotypes. A stable and economical source of IVD cells may include allogeneic MSCs from the cell bank for differentiation into IVD cells. Therefore, multiple alternative therapeutic options should be considered if a refined protocol for the differentiation of MSCs into IVD cells is established. In this study, we comprehensively reviewed the molecules, scaffolds, and environmental factors that facilitate the differentiation of MSCs into IVD cells for regenerative therapies for IDD.
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Affiliation(s)
- Takashi Ohnishi
- Department of Orthopedic Surgery, Faculty of Medicine and Graduate School of Medicine, Hokkaido University, Sapporo 060-8638, Japan; (T.O.); (K.H.); (A.F.); (N.I.)
| | - Kentaro Homan
- Department of Orthopedic Surgery, Faculty of Medicine and Graduate School of Medicine, Hokkaido University, Sapporo 060-8638, Japan; (T.O.); (K.H.); (A.F.); (N.I.)
| | - Akira Fukushima
- Department of Orthopedic Surgery, Faculty of Medicine and Graduate School of Medicine, Hokkaido University, Sapporo 060-8638, Japan; (T.O.); (K.H.); (A.F.); (N.I.)
| | - Daisuke Ukeba
- Department of Orthopedic Surgery, Hokkaido University Hospital, Sapporo 060-8648, Japan;
| | - Norimasa Iwasaki
- Department of Orthopedic Surgery, Faculty of Medicine and Graduate School of Medicine, Hokkaido University, Sapporo 060-8638, Japan; (T.O.); (K.H.); (A.F.); (N.I.)
| | - Hideki Sudo
- Department of Advanced Medicine for Spine and Spinal Cord Disorders, Faculty of Medicine and Graduate School of Medicine, Hokkaido University, Sapporo 060-8638, Japan
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Peng Y, Jiang H, Zuo HD. Factors affecting osteogenesis and chondrogenic differentiation of mesenchymal stem cells in osteoarthritis. World J Stem Cells 2023; 15:548-560. [PMID: 37424946 PMCID: PMC10324504 DOI: 10.4252/wjsc.v15.i6.548] [Citation(s) in RCA: 12] [Impact Index Per Article: 6.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/17/2023] [Revised: 04/21/2023] [Accepted: 05/05/2023] [Indexed: 06/26/2023] Open
Abstract
Osteoarthritis (OA) is a common degenerative joint disease that often involves progressive cartilage degeneration and bone destruction of subchondral bone. At present, clinical treatment is mainly for pain relief, and there are no effective methods to delay the progression of the disease. When this disease progresses to the advanced stage, the only treatment option for most patients is total knee replacement surgery, which causes patients great pain and anxiety. As a type of stem cell, mesenchymal stem cells (MSCs) have multidirectional differentiation potential. The osteogenic differentiation and chondrogenic differentiation of MSCs can play vital roles in the treatment of OA, as they can relieve pain in patients and improve joint function. The differentiation direction of MSCs is accurately controlled by a variety of signaling pathways, so there are many factors that can affect the differentiation direction of MSCs by acting on these signaling pathways. When MSCs are applied to OA treatment, the microenvironment of the joints, injected drugs, scaffold materials, source of MSCs and other factors exert specific impacts on the differentiation direction of MSCs. This review aims to summarize the mechanisms by which these factors influence MSC differentiation to produce better curative effects when MSCs are applied clinically in the future.
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Affiliation(s)
- Yi Peng
- Medical Imaging Key Laboratory of Sichuan Province, Department of Radiology, Affiliated Hospital of North Sichuan Medical College, Nanchong 637000, Sichuan Province, China
| | - Hai Jiang
- Medical Imaging Key Laboratory of Sichuan Province, Department of Radiology, Affiliated Hospital of North Sichuan Medical College, Nanchong 637000, Sichuan Province, China
| | - Hou-Dong Zuo
- Medical Imaging Key Laboratory of Sichuan Province, Department of Radiology, Affiliated Hospital of North Sichuan Medical College, Nanchong 637000, Sichuan Province, China
- Department of Radiology, Chengdu Xinhua Hospital, Chengdu 610067, Sichuan Province, China
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Zhang J, Zhang W, Sun T, Wang J, Li Y, Liu J, Li Z. The Influence of Intervertebral Disc Microenvironment on the Biological Behavior of Engrafted Mesenchymal Stem Cells. Stem Cells Int 2022; 2022:8671482. [PMID: 36387746 PMCID: PMC9663214 DOI: 10.1155/2022/8671482] [Citation(s) in RCA: 6] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/08/2022] [Revised: 10/19/2022] [Accepted: 10/25/2022] [Indexed: 12/01/2024] Open
Abstract
Intervertebral disc degeneration is the main cause of low back pain. Traditional treatment methods cannot repair degenerated intervertebral disc tissue. The emergence of stem cell therapy makes it possible to regenerate and repair degenerated intervertebral disc tissue. At present, mesenchymal stem cells are the most studied, and different types of mesenchymal stem cells have their own characteristics. However, due to the harsh and complex internal microenvironment of the intervertebral disc, it will affect the biological behaviors of the implanted mesenchymal stem cells, such as viability, proliferation, migration, and chondrogenic differentiation, thereby affecting the therapeutic effect. This review is aimed at summarizing the influence of each intervertebral disc microenvironmental factor on the biological behavior of mesenchymal stem cells, so as to provide new ideas for using tissue engineering technology to assist stem cells to overcome the influence of the microenvironment in the future.
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Affiliation(s)
- Jing Zhang
- Department of Orthopedics, First Affiliated Hospital of Dalian Medical University, Dalian, 116011 Liaoning, China
| | - Wentao Zhang
- Department of Orthopedics, First Affiliated Hospital of Dalian Medical University, Dalian, 116011 Liaoning, China
| | - Tianze Sun
- Department of Orthopedics, First Affiliated Hospital of Dalian Medical University, Dalian, 116011 Liaoning, China
| | - Jinzuo Wang
- Department of Orthopedics, First Affiliated Hospital of Dalian Medical University, Dalian, 116011 Liaoning, China
| | - Ying Li
- Stem Cell Clinical Research Centers, National Joint Engineering Laboratory, The First Affiliated Hospital of Dalian Medical University, Dalian, 116021 Liaoning, China
| | - Jing Liu
- Stem Cell Clinical Research Centers, National Joint Engineering Laboratory, The First Affiliated Hospital of Dalian Medical University, Dalian, 116021 Liaoning, China
| | - Zhonghai Li
- Department of Orthopedics, First Affiliated Hospital of Dalian Medical University, Dalian, 116011 Liaoning, China
- Stem Cell Clinical Research Centers, National Joint Engineering Laboratory, The First Affiliated Hospital of Dalian Medical University, Dalian, 116021 Liaoning, China
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Pham Le Khanh H, Nemes D, Rusznyák Á, Ujhelyi Z, Fehér P, Fenyvesi F, Váradi J, Vecsernyés M, Bácskay I. Comparative Investigation of Cellular Effects of Polyethylene Glycol (PEG) Derivatives. Polymers (Basel) 2022; 14:279. [PMID: 35054686 PMCID: PMC8779311 DOI: 10.3390/polym14020279] [Citation(s) in RCA: 20] [Impact Index Per Article: 6.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/08/2021] [Revised: 01/03/2022] [Accepted: 01/07/2022] [Indexed: 12/11/2022] Open
Abstract
Nowadays, polyethylene glycols referred to as PEGs are widely used in cosmetics, consumer care products, and the pharmaceutical industry. Their advantageous properties such as chemical stability, low immunogenicity, and high tolerability explain why PEGs are applied in many fields of pharmaceutical formulations including parenteral, topical, ophthalmic, oral, and rectal preparations and also in modern drug delivery systems. Given their extensive use, they are considered a well-known group of chemicals. However, the number of large-scale comparative studies involving multiple PEGs of wide molecular weight range is low, as in most cases biological effects are estimated upon molecular weight. The aim of this publication was to study the action of PEGs on Caco-2 cells and G. mellonella larvae and to calculate the correlation of these effects with molecular weight and osmolality. Eleven PEGs of different molecular weight were used in our experiments: PEG 200, PEG 300, PEG 400, PEG 600, PEG 1000, PEG 1500, PEG 4000, PEG 8000, PEG 10,000, 12,000, and PEG 20,000. The investigated cellular effects included cytotoxicity (MTT and Neutral Red assays, flow cytometry with propidium iodide and annexin V) and autophagy. The osmolality of different molecular weight PEGs with various concentrations was measured by a vapor pressure osmometer OSMOMAT 070 and G. mellonella larvae were injected with the solutions of PEGs. Sorbitol was used as controls of the same osmolality. Statistical correlation was calculated to describe the average molecular weight dependence of the different measured effects. Osmolality, the cytotoxicity assays, flow cytometry data, and larvae mortality had significant correlation with the structure of the PEGs, while autophagosome formation and the proportion of early apoptotic cells showed no statistical correlation. Overall, it must be noted that PEGs must be tested individually for biological effects as not all effects can be estimated by the average molecular weight.
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Affiliation(s)
- Ha Pham Le Khanh
- Department of Pharmaceutical Technology, Faculty of Pharmacy, University of Debrecen, Nagyerdei Körút 98, 4032 Debrecen, Hungary; (H.P.L.K.); (D.N.); (Á.R.); (Z.U.); (P.F.); (F.F.); (J.V.); (M.V.)
- Doctorate School of Pharmaceutical Sciences, University of Debrecen, Nagyerdei Körút 98, 4032 Debrecen, Hungary
- Institute of Healthcare Industry, University of Debrecen, Nagyerdei Körút 98, 4032 Debrecen, Hungary
| | - Dániel Nemes
- Department of Pharmaceutical Technology, Faculty of Pharmacy, University of Debrecen, Nagyerdei Körút 98, 4032 Debrecen, Hungary; (H.P.L.K.); (D.N.); (Á.R.); (Z.U.); (P.F.); (F.F.); (J.V.); (M.V.)
- Doctorate School of Pharmaceutical Sciences, University of Debrecen, Nagyerdei Körút 98, 4032 Debrecen, Hungary
| | - Ágnes Rusznyák
- Department of Pharmaceutical Technology, Faculty of Pharmacy, University of Debrecen, Nagyerdei Körút 98, 4032 Debrecen, Hungary; (H.P.L.K.); (D.N.); (Á.R.); (Z.U.); (P.F.); (F.F.); (J.V.); (M.V.)
- Doctorate School of Pharmaceutical Sciences, University of Debrecen, Nagyerdei Körút 98, 4032 Debrecen, Hungary
- Institute of Healthcare Industry, University of Debrecen, Nagyerdei Körút 98, 4032 Debrecen, Hungary
| | - Zoltán Ujhelyi
- Department of Pharmaceutical Technology, Faculty of Pharmacy, University of Debrecen, Nagyerdei Körút 98, 4032 Debrecen, Hungary; (H.P.L.K.); (D.N.); (Á.R.); (Z.U.); (P.F.); (F.F.); (J.V.); (M.V.)
- Doctorate School of Pharmaceutical Sciences, University of Debrecen, Nagyerdei Körút 98, 4032 Debrecen, Hungary
| | - Pálma Fehér
- Department of Pharmaceutical Technology, Faculty of Pharmacy, University of Debrecen, Nagyerdei Körút 98, 4032 Debrecen, Hungary; (H.P.L.K.); (D.N.); (Á.R.); (Z.U.); (P.F.); (F.F.); (J.V.); (M.V.)
- Doctorate School of Pharmaceutical Sciences, University of Debrecen, Nagyerdei Körút 98, 4032 Debrecen, Hungary
| | - Ferenc Fenyvesi
- Department of Pharmaceutical Technology, Faculty of Pharmacy, University of Debrecen, Nagyerdei Körút 98, 4032 Debrecen, Hungary; (H.P.L.K.); (D.N.); (Á.R.); (Z.U.); (P.F.); (F.F.); (J.V.); (M.V.)
- Doctorate School of Pharmaceutical Sciences, University of Debrecen, Nagyerdei Körút 98, 4032 Debrecen, Hungary
| | - Judit Váradi
- Department of Pharmaceutical Technology, Faculty of Pharmacy, University of Debrecen, Nagyerdei Körút 98, 4032 Debrecen, Hungary; (H.P.L.K.); (D.N.); (Á.R.); (Z.U.); (P.F.); (F.F.); (J.V.); (M.V.)
- Doctorate School of Pharmaceutical Sciences, University of Debrecen, Nagyerdei Körút 98, 4032 Debrecen, Hungary
| | - Miklós Vecsernyés
- Department of Pharmaceutical Technology, Faculty of Pharmacy, University of Debrecen, Nagyerdei Körút 98, 4032 Debrecen, Hungary; (H.P.L.K.); (D.N.); (Á.R.); (Z.U.); (P.F.); (F.F.); (J.V.); (M.V.)
- Doctorate School of Pharmaceutical Sciences, University of Debrecen, Nagyerdei Körút 98, 4032 Debrecen, Hungary
| | - Ildikó Bácskay
- Department of Pharmaceutical Technology, Faculty of Pharmacy, University of Debrecen, Nagyerdei Körút 98, 4032 Debrecen, Hungary; (H.P.L.K.); (D.N.); (Á.R.); (Z.U.); (P.F.); (F.F.); (J.V.); (M.V.)
- Doctorate School of Pharmaceutical Sciences, University of Debrecen, Nagyerdei Körút 98, 4032 Debrecen, Hungary
- Institute of Healthcare Industry, University of Debrecen, Nagyerdei Körút 98, 4032 Debrecen, Hungary
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Towards Physiologic Culture Approaches to Improve Standard Cultivation of Mesenchymal Stem Cells. Cells 2021; 10:cells10040886. [PMID: 33924517 PMCID: PMC8069108 DOI: 10.3390/cells10040886] [Citation(s) in RCA: 33] [Impact Index Per Article: 8.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/23/2021] [Revised: 04/09/2021] [Accepted: 04/12/2021] [Indexed: 02/07/2023] Open
Abstract
Mesenchymal stem cells (MSCs) are of great interest for their use in cell-based therapies due to their multipotent differentiation and immunomodulatory capacities. In consequence of limited numbers following their isolation from the donor tissue, MSCs require extensive expansion performed in traditional 2D cell culture setups to reach adequate amounts for therapeutic use. However, prolonged culture of MSCs in vitro has been shown to decrease their differentiation potential and alter their immunomodulatory properties. For that reason, preservation of these physiological characteristics of MSCs throughout their in vitro culture is essential for improving the efficiency of therapeutic and in vitro modeling applications. With this objective in mind, many studies already investigated certain parameters for enhancing current standard MSC culture protocols with regard to the effects of specific culture media components or culture conditions. Although there is a lot of diversity in the final therapeutic uses of the cells, the primary stage of standard isolation and expansion is imperative. Therefore, we want to review on approaches for optimizing standard MSC culture protocols during this essential primary step of in vitro expansion. The reviewed studies investigate and suggest improvements focused on culture media components (amino acids, ascorbic acid, glucose level, growth factors, lipids, platelet lysate, trace elements, serum, and xenogeneic components) as well as culture conditions and processes (hypoxia, cell seeding, and dissociation during passaging), in order to preserve the MSC phenotype and functionality during the primary phase of in vitro culture.
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Hyperosmolarity benefits cartilage regeneration by enhancing expression of chondrogenic markers and reducing inflammatory markers. In Vitro Cell Dev Biol Anim 2021; 57:290-299. [PMID: 33580417 DOI: 10.1007/s11626-020-00430-z] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/12/2019] [Accepted: 01/07/2020] [Indexed: 10/22/2022]
Abstract
Application of hyperosmolarity can be a promising strategy to promote chondrogenic differentiation in adipose-derived mesenchymal stem cells (ADSCs). Growth factors may promote different signaling pathways in parallel that is why in this study we monitor undesired pathologic or unwanted side effects as well as chondroinductive impacts of hyperosmolarity in differentiating ADSCs. Quantified gene expression, immunocytochemistry, glycosaminoglycan deposition and angiogenic secretion assays performed along with immunoassay. We observed that hyperosmolarity pressure of 480 mOsm over-expressed cartilage specific markers at gene expression level in the extra cellular matrix. Meanwhile, hyperosmolarity of 480 mOsm diminished the expression of cartilage associated pathologic markers, i.e., inflammatory and angiogenic attributes. Certain dose of hyperosmolarity could benefit chondrogenesis in a dual way, first by increasing chondrogenic markers and second by lowering tissue mineralization and angiogenic potential. The chondroprotective potential of hyperosmolarity could have a promising benefit in cartilage cell therapy and tissue engineering.
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Saghati S, Nasrabadi HT, Khoshfetrat AB, Moharamzadeh K, Hassani A, Mohammadi SM, Rahbarghazi R, Fathi Karkan S. Tissue Engineering Strategies to Increase Osteochondral Regeneration of Stem Cells; a Close Look at Different Modalities. Stem Cell Rev Rep 2021; 17:1294-1311. [PMID: 33547591 DOI: 10.1007/s12015-021-10130-0] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 01/26/2021] [Indexed: 02/06/2023]
Abstract
The homeostasis of osteochondral tissue is tightly controlled by articular cartilage chondrocytes and underlying subchondral bone osteoblasts via different internal and external clues. As a correlate, the osteochondral region is frequently exposed to physical forces and mechanical pressure. On this basis, distinct sets of substrates and physicochemical properties of the surrounding matrix affect the regeneration capacity of chondrocytes and osteoblasts. Stem cells are touted as an alternative cell source for the alleviation of osteochondral diseases. These cells appropriately respond to the physicochemical properties of different biomaterials. This review aimed to address some of the essential factors which participate in the chondrogenic and osteogenic capacity of stem cells. Elements consisted of biomechanical forces, electrical fields, and biochemical and physical properties of the extracellular matrix are the major determinant of stem cell differentiation capacity. It is suggested that an additional certain mechanism related to signal-transduction pathways could also mediate the chondro-osteogenic differentiation of stem cells. The discovery of these clues can enable us to modulate the regeneration capacity of stem cells in osteochondral injuries and lead to the improvement of more operative approaches using tissue engineering modalities.
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Affiliation(s)
- Sepideh Saghati
- Stem Cell Research Center, Tabriz University of Medical Sciences, Tabriz, Iran.,Department of Tissue Engineering, Faculty of Advanced Medical Sciences, Tabriz University of Medical Sciences, Tabriz, Iran
| | - Hamid Tayefi Nasrabadi
- Stem Cell Research Center, Tabriz University of Medical Sciences, Tabriz, Iran. .,Department of Tissue Engineering, Faculty of Advanced Medical Sciences, Tabriz University of Medical Sciences, Tabriz, Iran.
| | - Ali Baradar Khoshfetrat
- Stem Cell Research Center, Tabriz University of Medical Sciences, Tabriz, Iran. .,Department of Tissue Engineering, Faculty of Advanced Medical Sciences, Tabriz University of Medical Sciences, Tabriz, Iran.
| | - Keyvan Moharamzadeh
- Hamdan Bin Mohammed College of Dental Medicine (HBMCDM), Mohammed Bin Rashid University of Medicine and Health Sciences (MBRU), Dubai, United Arab Emirates
| | - Ayla Hassani
- Chemical Engineering Faculty, Sahand University of Technology, Tabriz, 51335-1996, Iran
| | - Seyedeh Momeneh Mohammadi
- Department of Anatomical Sciences, School of Medicine, Zanjan University of Medical Sciences, Zanjan, Iran
| | - Reza Rahbarghazi
- Stem Cell Research Center, Tabriz University of Medical Sciences, Tabriz, Iran. .,Department of Applied Cell Sciences, Faculty of Advanced Medical Sciences, Tabriz University of Medical Sciences, Tabriz, Iran.
| | - Sonia Fathi Karkan
- Department of Medical Nanotechnology, Faculty of Advanced Medical Sciences, Tabriz University of Medical Sciences, Tabriz, Iran.,Student Research Committee, Tabriz University of Medical Sciences, Tabriz, Iran
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Farhang N, Silverman L, Bowles RD. Improving Cell Therapy Survival and Anabolism in Harsh Musculoskeletal Disease Environments. TISSUE ENGINEERING PART B-REVIEWS 2020; 26:348-366. [PMID: 32070243 DOI: 10.1089/ten.teb.2019.0324] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 12/25/2022]
Abstract
Cell therapies are an up and coming technology in orthopedic medicine that has the potential to provide regenerative treatments for musculoskeletal disease. Despite numerous cell therapies showing preclinical success for common musculoskeletal indications of disc degeneration and osteoarthritis, there have been mixed results when testing these therapies in humans during clinical trials. A theory behind the mixed success of these cell therapies is that the harsh microenvironments of the disc and knee they are entering inhibit their anabolism and survival. Therefore, there is much ongoing research looking into how to improve the survival and anabolism of cell therapies within these musculoskeletal disease environments. This includes research into improving cell function under specific microenvironmental conditions known to exist in the intervertebral disc (IVD) and knee environment such as hypoxia, low-nutrient conditions, hyperosmolarity, acidity, and inflammation. This research also includes improving differentiation of cells into desired native cell phenotypes to better enhance their survival and anabolism in the knee and IVD. This review highlights the effects of specific musculoskeletal microenvironmental challenges on cell therapies and what research is being done to overcome these challenges. Impact statement While there has been significant clinical interest in using cell therapies for musculoskeletal pathologies in the knee and intervertebral disc, cell therapy clinical trials have had mixed outcomes. The information presented in this review includes the environmental challenges (i.e., acidic pH, inflammation, hyperosmolarity, hypoxia, and low nutrition) that cell therapies experience in these pathological musculoskeletal environments. This review summarizes studies that describe various approaches to improving the therapeutic capability of cell therapies in these harsh environments. The result is an overview of what approaches can be targeted and/or combined to develop a more consistent cell therapy for musculoskeletal pathologies.
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Affiliation(s)
- Niloofar Farhang
- Department of Biomedical Engineering, University of Utah, Salt Lake City, Utah, USA
| | | | - Robby D Bowles
- Department of Biomedical Engineering, University of Utah, Salt Lake City, Utah, USA
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Aslani S, Kabiri M, Kehtari M, Hanaee-Ahvaz H. Vascular tissue engineering: Fabrication and characterization of acetylsalicylic acid-loaded electrospun scaffolds coated with amniotic membrane lysate. J Cell Physiol 2019; 234:16080-16096. [PMID: 30779117 DOI: 10.1002/jcp.28266] [Citation(s) in RCA: 28] [Impact Index Per Article: 4.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/12/2017] [Revised: 12/26/2018] [Accepted: 01/10/2019] [Indexed: 01/24/2023]
Abstract
As the incidence of small-diameter vascular graft (SDVG) occlusion is considerably high, a great amount of research is focused on constructing a more biocompatible graft. The absence of a biocompatible surface in the lumen of the engineered grafts that can support confluent lining with endothelial cells (ECs) can cause thrombosis and graft failure. Blood clot formation is mainly because of the lack of an integrated endothelium. The most effective approach to combat this problem would be using natural extracellular matrix constituents as a mimic of endothelial basement membrane along with applying anticoagulant agents to provide local antithrombotic effects. In this study, we fabricated aligned and random electrospun poly-L-lactic acid (PLLA) scaffolds containing acetylsalicylic acid (ASA) as the anticoagulation agent and surface coated them with amniotic membrane (AM) lysate. Vascular scaffolds were structurally and mechanically characterized and assessed for cyto- and hemocompatibility and their ability to support endothelial differentiation was examined. All the scaffolds showed appropriate tensile strength as expected for vascular grafts. Lack of cytotoxicity, cellular attachment, growth, and infiltration were proved using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay and scanning electron microscopy. The blood compatibilities of different scaffolds examined by in vitro hemolysis and blood coagulation assays elucidated the excellent hemocompatibility of our novel AM-coated ASA-loaded nanofibers. Drug-loaded scaffolds showed a sustained release profile of ASA in 7 days. AM-coated electrospun PLLA fibers showed enhanced cytocompatibility for human umbilical vein ECs, making a confluent endothelial-like lining. In addition, AM lysate-coated ASA-PLLA-aligned scaffold proved to support endothelial differentiation of Wharton's jelly-derived mesenchymal stem cells. Our results together indicated that AM lysate-coated ASA releasing scaffolds have promising potentials for development of a biocompatible SDVG.
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Affiliation(s)
- Saba Aslani
- Department of Biotechnology, College of Science, University of Tehran, Tehran, Iran.,Department of Neurology and Neurosurgery, McGill University, Quebec, Canada.,Department of Molecular biology and genetic engineering and Department of nanotechnology and tissue engineering, Stem Cell Technology Research Center, Tehran, Iran
| | - Mahboubeh Kabiri
- Department of Biotechnology, College of Science, University of Tehran, Tehran, Iran
| | - Mousa Kehtari
- Department of Molecular biology and genetic engineering and Department of nanotechnology and tissue engineering, Stem Cell Technology Research Center, Tehran, Iran.,Developmental Biology Laboratory, School of Biology, College of Science, University of Tehran, Tehran, Iran
| | - Hana Hanaee-Ahvaz
- Department of Molecular biology and genetic engineering and Department of nanotechnology and tissue engineering, Stem Cell Technology Research Center, Tehran, Iran
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Hall AC. The Role of Chondrocyte Morphology and Volume in Controlling Phenotype-Implications for Osteoarthritis, Cartilage Repair, and Cartilage Engineering. Curr Rheumatol Rep 2019; 21:38. [PMID: 31203465 PMCID: PMC6571082 DOI: 10.1007/s11926-019-0837-6] [Citation(s) in RCA: 113] [Impact Index Per Article: 18.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/16/2022]
Abstract
PURPOSE OF REVIEW Articular chondrocytes are exclusively responsible for the turnover of the extracellular matrix (ECM) of hyaline cartilage. However, chondrocytes are phenotypically unstable and, if they de-differentiate into hypertrophic or fibroblastic forms, will produce a defective and weak matrix. Chondrocyte volume and morphology exert a strong influence over phenotype and a full appreciation of the factors controlling chondrocyte phenotype stability is central to understanding (a) the mechanisms underlying the cartilage failure in osteoarthritis (OA), (b) the rationale for hyaline cartilage repair, and (c) the strategies for improving the engineering of resilient cartilage. The focus of this review is on the factors involved in, and the importance of regulating, chondrocyte morphology and volume as key controllers of chondrocyte phenotype. RECENT FINDINGS The visualisation of fluorescently-labelled in situ chondrocytes within non-degenerate and mildly degenerate cartilage, by confocal scanning laser microscopy (CLSM) and imaging software, has identified the marked heterogeneity of chondrocyte volume and morphology. The presence of chondrocytes with cytoplasmic processes, increased volume, and clustering suggests important early changes to their phenotype. Results from experiments more closely aligned to the normal physico-chemical environment of in situ chondrocytes are emphasising the importance of understanding the factors controlling chondrocyte morphology and volume that ultimately affect phenotype. An appreciation of the importance of chondrocyte volume and morphology for controlling the chondrocyte phenotype is advancing at a rapid pace and holds particular promise for developing strategies for protecting the chondrocytes against deleterious changes and thereby maintaining healthy and resilient cartilage.
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Affiliation(s)
- Andrew C Hall
- Deanery of Biomedical Sciences, University of Edinburgh, Hugh Robson Building, George Square, Edinburgh, Scotland, EH8 9XD, UK.
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Kazem-Arki M, Kabiri M, Rad I, Roodbari NH, Hosseinpoor H, Mirzaei S, Parivar K, Hanaee-Ahvaz H. Enhancement of osteogenic differentiation of adipose-derived stem cells by PRP modified nanofibrous scaffold. Cytotechnology 2018; 70:1487-1498. [PMID: 30083791 PMCID: PMC6269372 DOI: 10.1007/s10616-018-0226-4] [Citation(s) in RCA: 17] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/10/2018] [Accepted: 05/03/2018] [Indexed: 12/26/2022] Open
Abstract
Recent developments in bone tissue engineering have paved the way for more efficient and cost-effective strategies. Additionally, utilization of autologous sources has been considered very desirable and is increasingly growing. Recently, activated platelet rich plasma (PRP) has been widely used in the field of bone tissue engineering, since it harbours a huge number of growth factors that can enhance osteogenesis and bone regeneration. In the present study, the osteogenic effects of PRP coated nanofibrous PES/PVA scaffolds on adipose-derived mesenchymal stem cells have been investigated. Common osteogenic markers were assayed by real time PCR. Alkaline phosphate activity, calcium deposition and Alizarin red staining assays were performed as well. The results revealed that the highest osteogenic differentiation occurred when cells were cultured on PRP coated PES/PVA scaffolds. Interestingly, direct application of PRP to culture media had no additive effects on osteogenesis of cells cultured on PRP coated PES/PVA scaffolds or those receiving typical osteogenic factors. The highest osteogenic effects were achieved by the simplest and most cost-effective method, i.e. merely by using PRP coated scaffolds. PRP coated PES/PVA scaffolds can maximally induce osteogenesis with no need for extrinsic factors. The major contribution of this paper to the current researches on bone regeneration is to suggest an easy, cost-effective approach to enhance osteogenesis via PRP coated scaffolds, with no additional external growth factors.
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Affiliation(s)
- Mandana Kazem-Arki
- Department of Biology, Science and Research Branch, Islamic Azad University, Tehran, Iran
| | - Mahboubeh Kabiri
- Department of Biotechnology, College of Science, University of Tehran, Tehran, Iran
| | - Iman Rad
- Stem Cell Technology Research Center, Tehran, Iran
| | - Nasim Hayati Roodbari
- Department of Biology, Science and Research Branch, Islamic Azad University, Tehran, Iran.
| | | | | | - Kazem Parivar
- Department of Biology, Science and Research Branch, Islamic Azad University, Tehran, Iran
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