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Di Gesù R, Palumbo Piccionello A, Vitale G, Buscemi S, Panzavolta S, Di Filippo MF, Leonarda A, Cuccia M, Di Prima A, Gottardi R. Biofabrication of an in situhypoxia-delivery scaffold for cartilage regeneration. Biofabrication 2025; 17:025025. [PMID: 40048828 DOI: 10.1088/1758-5090/adbd79] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/09/2024] [Accepted: 03/06/2025] [Indexed: 03/14/2025]
Abstract
Osteoarthritis (OA) is a debilitating joint condition affecting millions of people worldwide, triggering painful chondral defects (CDs) that ultimately compromise the overarching patients' quality of life. Currently, several reconstructive cartilage techniques (RCTs) (i.e.: matrix-assisted autologous chondrocytes implantation has been developed to overcome the total joint replacement limitations in the treatment of CDs. However, there is no consensus on the effectiveness of RCTs in the long term, as they do not provide adequate pro-regenerative stimuli to ensure complete CDs healing. In this study, we describe the biofabrication of an innovative scaffold capable to promote the CDs healing by delivering pro-regenerative hypoxic cues at the cellular/tissue level, to be used during RCTs. The scaffold is composed of a gelatin methacrylate (GelMA) matrix doped with hypoxic seeds of GelMA functionalized with a fluorinated oxadiazole (GelOXA), which ensures the delivery of hypoxic cues to human articular chondrocytes (hACs) embedded within the scaffold. We found that the GelMA/GelOXA scaffold preserved hACs viability, maintained their native phenotype, and significantly improved the production of type II collagen. Besides, we observed a reduction in type I and type X collagen, characteristic of unhealthy cartilage. These findings pave the way for the regeneration of healthy, hyaline-like cartilage, by delivering hypoxic cues even under normoxic conditions. Furthermore, the GelMA/GelOXA scaffold's ability to deliver healing signals directly to the injury site holds great potential for treating OA and related CDs, and has the potential to revolutionize the field of cartilage repair and regenerative medicine.
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Affiliation(s)
- R Di Gesù
- Musculoskeletal Tissue Engineering (MsTE) Laboratory, Ri.MED Foundation, Palermo, Italy
| | | | - G Vitale
- Musculoskeletal Tissue Engineering (MsTE) Laboratory, Ri.MED Foundation, Palermo, Italy
| | - S Buscemi
- Organic Chemistry Department, University of Palermo, Palermo, Italy
| | - S Panzavolta
- Organic Chemistry Department, University of Bologna, Bologna, Italy
| | - M F Di Filippo
- Organic Chemistry Department, University of Bologna, Bologna, Italy
| | - A Leonarda
- Orthopedic Surgery Department, Buccheri La Ferla Hospital, Palermo, Italy
| | - M Cuccia
- Orthopedic Surgery Department, Buccheri La Ferla Hospital, Palermo, Italy
| | - A Di Prima
- Pathological Anatomy Laboratory, IRCSSS ISMETT, Palermo, Italy
| | - R Gottardi
- Musculoskeletal Tissue Engineering (MsTE) Laboratory, Ri.MED Foundation, Palermo, Italy
- Department of Bioengineering, University of Pennsylvania, Philadelphia, PA, United States of America
- Children's Hospital of Philadelphia (CHOP), Philadelphia, PA, United States of America
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2
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Fu Z, Lai Y, Zhuang Y, Lin F. Injectable heat-sensitive nanocomposite hydrogel for regulating gene expression in the treatment of alcohol-induced osteonecrosis of the femoral head. APL Bioeng 2023; 7:016107. [PMID: 36691581 PMCID: PMC9862308 DOI: 10.1063/5.0130711] [Citation(s) in RCA: 10] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/14/2022] [Accepted: 12/20/2022] [Indexed: 01/19/2023] Open
Abstract
For repairing lesions, it is important to recover physiological and cellular activities. Gene therapy can restore these activities by regulating the expression of genes in lesion cells; however, in chronic diseases, such as alcohol-induced osteonecrosis of the femoral head (ONFH), gene therapy has failed to provide long-term effects. In this study, we developed a heat-sensitive nanocomposite hydrogel system with a secondary nanostructure that can regulate gene expression and achieve long-term gene regulation in lesion cells. This nanocomposite hydrogel exists in a liquid state at 25 °C and is injectable. Once injected into the body, the hydrogel can undergo solidification induced by body heat, thereby gaining the ability to be retained in the body for a prolonged time period. With the gradual degradation of the hydrogel in vivo, the internal secondary nanostructures are continuously released. These nanoparticles carry plasmids and siRNA into lesion stem cells to promote the expression of B-cell lymphoma 2 (inhibiting the apoptosis of stem cells) and inhibit the secretion of peroxisome proliferators-activated receptors γ (PPARγ, inhibiting the adipogenic differentiation of stem cells). Finally, the physiological activity of the stem cells in the ONFH area was restored and ONFH repair was promoted. In vivo experiments demonstrated that this nanocomposite hydrogel can be indwelled for a long time, thereby providing long-term treatment effects. As a result, bone reconstruction occurs in the ONFH area, thus enabling the treatment of alcohol-induced ONFH. Our nanocomposite hydrogel provides a novel treatment option for alcohol-related diseases and may serve as a useful biomaterial for other gene therapy applications.
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Affiliation(s)
- Zherui Fu
- Department of Emergency, The First People's
Hospital of Xiaoshan District, Xiaoshan Affiliated Hospital of Wenzhou
Medical University, Hangzhou, Zhejiang,
China
| | - Yi Lai
- Department of Emergency, The First People's
Hospital of Xiaoshan District, Xiaoshan Affiliated Hospital of Wenzhou
Medical University, Hangzhou, Zhejiang,
China
| | - Yaping Zhuang
- Department of Orthopedics, Shanghai Key Laboratory
for Prevention and Treatment of Bone and Joint Diseases, Shanghai Institute
of Traumatology and Orthopedics, Ruijin Hospital, Shanghai Jiao Tong
University School of Medicine, 197 Ruijin 2nd Road, Shanghai
200025, People's Republic of China.,Authors to whom correspondence should be
addressed: and
| | - Feng Lin
- Department of Orthopedics, The First
People's Hospital of Xiaoshan District, Xiaoshan Affiliated Hospital
of Wenzhou Medical University, Hangzhou, Zhejiang,
China,Authors to whom correspondence should be
addressed: and
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3
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Tissue Engineering of Canine Cartilage from Surgically Debrided Osteochondritis Dissecans Fragments. Ann Biomed Eng 2021; 50:56-77. [PMID: 34961892 PMCID: PMC8763830 DOI: 10.1007/s10439-021-02897-7] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/14/2021] [Accepted: 11/21/2021] [Indexed: 11/30/2022]
Abstract
This study in dogs explored the feasibility of using cartilage fragments removed and discarded during routine palliative surgery for osteochondritis dissecans (OCD) as a source of primary chondrocytes for scaffold-free cartilage tissue-engineering. Primary chondrocytes were obtained from three OCD donors and one age-matched healthy articular cartilage (HAC) donor. After monolayer expansion of primary cells, a three-dimensional spherical suspension culture was implemented. Following this stage, cells were seeded at a high density into custom-made agarose molds that allowed for size and shape-specific constructs to be generated via a method of cellular self-assembling in a scaffold-free environment. Fifty-eight neocartilage constructs were tissue-engineered using this methodology. Neocartilage constructs and native cartilage from shoulder joint were subjected to histological, mechanical, and biochemical testing. OCD and HAC chondrocytes-sourced constructs had uniformly flat morphology and histology consistent with cartilage tissue. Constructs sourced from OCD chondrocytes were 1.5-times (32%) stiffer in compression and 1.3 times (23%) stronger in tension than constructs sourced from HAC chondrocytes and only 8.7-times (81%) less stiff in tension than native tissue. Constructs from both cell sources consistently had lower collagen content than native tissue (22.9%/dry weight [DW] for OCD and 4.1%/DW for HAC vs. 51.1%/DW native tissue). To improve the collagen content and mechanical properties of neocartilage, biological and mechanical stimuli, and thyroid hormone (tri-iodothyronine) were applied to the chondrocytes during the self-assembling stage in two separate studies. A 2.6-fold (62%) increase in compressive stiffness was detected with supplementation of biological stimuli alone and 5-fold (81%) increase with combined biological and mechanical stimuli at 20% strain. Application of thyroid hormone improved collagen content (1.7-times, 33%), tensile strength (1.8-times, 43%), and stiffness (1.3-times, 21%) of constructs, relative to untreated controls. Collectively, these data suggest that OCD chondrocytes can serve as a reliable cell source for cartilage tissue-engineering and that canine chondrocytes respond favorably to biological and mechanical stimuli that have been shown effective in chondrocytes from other animal species, including humans.
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Zhang Z, Lin S, Yan Y, You X, Ye H. Enhanced efficacy of transforming growth factor-β1 loaded an injectable cross-linked thiolated chitosan and carboxymethyl cellulose-based hydrogels for cartilage tissue engineering. JOURNAL OF BIOMATERIALS SCIENCE-POLYMER EDITION 2021; 32:2402-2422. [PMID: 34428384 DOI: 10.1080/09205063.2021.1971823] [Citation(s) in RCA: 11] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 12/23/2022]
Abstract
Growth factors (GFs) are soluble proteins extracellular that control a wide range of cellular processes as well as tissue regeneration. While transforming growth factor beta-1 (TGF-β1) promotes chondrogenesis, its medical use is restricted by its potential protein instability, which necessitates high doses of the protein, which can result in adverse side effects such as inefficient cartilage formation. In this work, we have developed a novel hydrogel composite based on the polymer, cross-linked thiolated chitosan; TCS and carboxymethyl cellulose; CMC (TCS/CMC) hydrogel system was utilized as injectable TGF-β1 carriers for cartilage tissue engineering applications. Rheological measurements showed that the elastic modulus of TCS/CMC hydrogels with an optimized CMC concentration could reach around 2.5 kPa or higher than their respective viscous modulus, indicating that they behaved like strong hydrogels. Crosslinking significantly alters the overall network distribution, surface morphology, pore size, porosity, gelation time, swelling ratio, water content, and in vitro degradation of the TCS/CMC hydrogels. TCS/CMC hydrogels maintain more than 90% of their weight and retain their original form after 21 days. TGF-β1 released marginally from TCS/CMC hydrogels as incubation time increased, up to 21 days, with around 18.6 ± 0.9% of the drug stored inside the TCS/CMC hydrogels. On day 21, BMSC treated with TGF-β1 in medium or TGF-β1-loaded TCS/CMC hydrogels grew faster than the other groups. For in vivo cartilage repair, full-thickness cartilage defects were induced on rat knees for 8 weeks. The optimal ability of this novel TGF-β1-loaded TCS/CMC hydrogel system was further demonstrated by histological analysis, resulting in a novel therapeutic strategy for repairing articular cartilage defects.Research HighlightsAn in situ forming and injectable thiolated chitosan and carboxymethyl cellulose hydrogel was fabricated for cartilage tissue engineering.TCS/CMC displays suitable gelation time with high swelling ratio, tunable mechanical properties and highly porous.TGF-β1-loaded-TCS/CMC hydrogels showed maximum drug release activity.TGF-β1-loaded-TCS/CMC hydrogels had good biocompatibility to articular chondrocytes.An injectable TCS/CMC/TGF-β1 hydrogel is a promising material system for cartilage tissue engineering.
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Affiliation(s)
- Zefeng Zhang
- Department of Orthopedics, The Second Affiliated Hospital of Fujian Medical University, Fujian, PR China
| | - Shufeng Lin
- Department of Orthopedics, The Second Affiliated Hospital of Fujian Medical University, Fujian, PR China
| | - Yipeng Yan
- Department of Orthopedics, The Second Affiliated Hospital of Fujian Medical University, Fujian, PR China
| | - Xiaoxuan You
- Department of Orthopedics, The Second Affiliated Hospital of Fujian Medical University, Fujian, PR China
| | - Hui Ye
- Department of Orthopedics, The Second Affiliated Hospital of Fujian Medical University, Fujian, PR China
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5
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Souza ARM, Castro ADAE, Fonseca EKUN, Nunes LMAO, Baptista E, Hartmann LGDC. Magnetic resonance imaging aspects after surgical repair of knee cartilage: pictorial essay. Radiol Bras 2020; 53:201-207. [PMID: 32587430 PMCID: PMC7302905 DOI: 10.1590/0100-3984.2019.0020] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/18/2023] Open
Abstract
Radiologists should be familiar with the main techniques of knee cartilage repair and the imaging methods available for its evaluation, in order to optimize the postoperative follow-up of patients. The objective of this study was to present a series of clinical cases seen at our facility, illustrating the main techniques necessary for the repair of knee cartilage, as well as the magnetic resonance imaging techniques used in the postoperative evaluation and the relevant radiological findings.
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Affiliation(s)
| | | | | | | | - Eduardo Baptista
- Departamento de Imagem - Hospital Israelita Albert Einstein, São Paulo, SP, Brazil
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6
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Kunze KN, Burnett RA, Wright-Chisem J, Frank RM, Chahla J. Adipose-Derived Mesenchymal Stem Cell Treatments and Available Formulations. Curr Rev Musculoskelet Med 2020; 13:264-280. [PMID: 32328959 DOI: 10.1007/s12178-020-09624-0] [Citation(s) in RCA: 11] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/13/2022]
Abstract
PURPOSE OF REVIEW The use of human adipose-derived mesenchymal stem cells (ADSCs) has gained attention due to its potential to expedite healing and the ease of harvesting; however, clinical evidence is limited, and questions concerning optimal method of delivery and long-term outcomes remain unanswered. RECENT FINDINGS Administration of ADSCs in animal models has been reported to aid in improved healing benefits with enhanced repair biomechanics, superior gross histological appearance of injury sites, and higher concentrations of growth factors associated with healing compared to controls. Recently, an increasing body of research has sought to examine the effects of ADSCs in humans. Several available processing techniques and formulations for ADSCs exist with evidence to suggest benefits with the use of ADSCs, but the superiority of any one method is not clear. Evidence from the most recent clinical studies available demonstrates promising outcomes following treatment of select musculoskeletal pathologies with ADSCs despite reporting variability among ADSCs harvesting and processing; these include (1) healing benefits and pain improvement for rotator cuff and Achilles tendinopathies, (2) improvements in pain and function in those with knee and hip osteoarthritis, and (3) improved cartilage regeneration for osteochondral focal defects of the knee and talus. The limitation to most of this literature is the use of other therapeutic biologics in combination with ADSCs. Additionally, many studies lack control groups, making establishment of causation inappropriate. It is imperative to perform higher-quality studies using consistent, predictable control populations and to standardize formulations of ADSCs in these trials.
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Affiliation(s)
- Kyle N Kunze
- Department of Orthopaedic Surgery, Division of Sports Medicine, Rush University Medical Center, Chicago, IL, USA
| | - Robert A Burnett
- Department of Orthopaedic Surgery, Division of Sports Medicine, Rush University Medical Center, Chicago, IL, USA
| | - Joshua Wright-Chisem
- Department of Orthopaedic Surgery, Hospital for Special Surgery, New York, NY, USA
| | - Rachel M Frank
- Department of Orthopaedic Surgery, Division of Sports Medicine, University of Colorado School of Medicine, Boulder, CO, USA
| | - Jorge Chahla
- Department of Orthopaedic Surgery, Division of Sports Medicine, Rush University Medical Center, Chicago, IL, USA.
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7
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Li Q, Chen X, Li J. Marrow-derived mesenchymal stem cells regulate the inflammatory response and repair alveolar type II epithelial cells in acute lung injury of rats. J Int Med Res 2020; 48:300060520909027. [PMID: 32314638 PMCID: PMC7175070 DOI: 10.1177/0300060520909027] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/15/2022] Open
Abstract
Objective We investigated the effect of untransplantable bone marrow-derived mesenchymal stem cells (BMSCs) in acute lung injury (ALI) and whether BMSCs attenuate damage of lipopolysaccharide (LPS) to alveolar type II epithelial cells (AECIIs). Methods ALI models were prepared by nebulizing LPS and then BMSCs were infused 1 hour later. We observed histopathological changes of lung tissue and evaluated inflammatory exudation by the wet/dry weight ratio, bronchiolar lavage fluid cell count, and protein concentration determination. Inflammatory and vascular factors were detected by immunohistochemistry and western blotting. For in vitro experiments, AECIIs were stimulated with 10 μg/mL LPS for 4 hours and then BMSCs were seeded in transit inserts to co-culture for 24 hours. The activity of AECIIs was detected. Results In the LPS + BMSCs group, histopathological examination showed that the degree of lung injury was significantly reduced compared with the LPS group. Protein expression of inflammatory and vascular factors was significantly lower with treatment. Optical density values and cell viability of the LPS + BMSCs group were significantly higher than those of the LPS group. Conclusions Untransplanted-BMSCs can inhibit the inflammatory response in ALI and promote repair of AECIIs. This might be due to substances secreted by BMSCs and interaction between these substances.
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Affiliation(s)
- Qianying Li
- Department of Pediatrics, Shengjing Hospital of China Medical University, Shenyang, China.,Department of Pediatric Intensive Care Unit (PICU), Children's Hospital Affiliated to Zhengzhou University, Henan Children's Hospital, Zhengzhou Children's Hospital, Zhengzhou, Henan, China
| | | | - Jiujun Li
- Department of Pediatrics, Shengjing Hospital of China Medical University, Shenyang, China
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8
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Small animal models to understand pathogenesis of osteoarthritis and use of stem cell in cartilage regeneration. Cell Biochem Funct 2017; 35:3-11. [DOI: 10.1002/cbf.3246] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/01/2016] [Revised: 11/06/2016] [Accepted: 12/04/2016] [Indexed: 01/05/2023]
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9
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Reissis D, Tang QO, Cooper NC, Carasco CF, Gamie Z, Mantalaris A, Tsiridis E. Current clinical evidence for the use of mesenchymal stem cells in articular cartilage repair. Expert Opin Biol Ther 2016; 16:535-57. [PMID: 26798997 DOI: 10.1517/14712598.2016.1145651] [Citation(s) in RCA: 33] [Impact Index Per Article: 3.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/13/2023]
Abstract
INTRODUCTION Articular cartilage is renowned for its poor intrinsic capacity for repair. Current treatments for osteoarthritis are limited in their ability to reliably restore the native articular cartilage structure and function. Mesenchymal stem cells (MSCs) present an attractive treatment option for articular cartilage repair, with a recent expansion of clinical trials investigating their use in patients. AREAS COVERED This paper provides a current overview of the clinical evidence on the use of MSCs in articular cartilage repair. EXPERT OPINION The article demonstrates robust clinical evidence that MSCs have significant potential for the regeneration of hyaline articular cartilage in patients. The majority of clinical trials to date have yielded significantly positive results with minimal adverse effects. However the clinical research is still in its infancy. The optimum MSC source, cell concentrations, implantation technique, scaffold, growth factors and rehabilitation protocol for clinical use are yet to be identified. A larger number of randomised control trials are required to objectively compare the clinical efficacy and long-term safety of the various techniques. As the clinical research continues to evolve and address these challenges, it is likely that MSCs may become integrated into routine clinical practice in the near future.
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Affiliation(s)
- Dimitris Reissis
- a Department of Chemical Engineering, Biological Systems Engineering Laboratory (BSEL) , Imperial College London , London , UK
| | - Quen Oak Tang
- a Department of Chemical Engineering, Biological Systems Engineering Laboratory (BSEL) , Imperial College London , London , UK
| | - Nina Catherine Cooper
- a Department of Chemical Engineering, Biological Systems Engineering Laboratory (BSEL) , Imperial College London , London , UK
| | - Clare Francesca Carasco
- a Department of Chemical Engineering, Biological Systems Engineering Laboratory (BSEL) , Imperial College London , London , UK
| | - Zakareya Gamie
- a Department of Chemical Engineering, Biological Systems Engineering Laboratory (BSEL) , Imperial College London , London , UK
| | - Athanasios Mantalaris
- a Department of Chemical Engineering, Biological Systems Engineering Laboratory (BSEL) , Imperial College London , London , UK
| | - Eleftherios Tsiridis
- a Department of Chemical Engineering, Biological Systems Engineering Laboratory (BSEL) , Imperial College London , London , UK.,b Academic Orthopaedic Unit , Aristotle University Medical School , Thessaloniki , Greece
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10
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Shao J, Zhang W, Yang T. Using mesenchymal stem cells as a therapy for bone regeneration and repairing. Biol Res 2015; 48:62. [PMID: 26530042 PMCID: PMC4630918 DOI: 10.1186/s40659-015-0053-4] [Citation(s) in RCA: 60] [Impact Index Per Article: 6.0] [Reference Citation Analysis] [Abstract] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/21/2015] [Accepted: 10/22/2015] [Indexed: 02/07/2023] Open
Abstract
Bone is a unique tissue which could regenerate completely after injury rather than heal itself with a scar. Compared with other tissues the difference is that, during bone repairing and regeneration, after the inflammatory phase the mesenchymal stem cells (MSCs) are recruited to the injury site and differentiate into either chondroblasts or osteoblasts precursors, leading to bone repairing and regeneration. Besides these two precursors, the MSCs can also differentiate into adipocyte precursors, skeletal muscle precursors and some other mesodermal cells. With this multilineage potentiality, the MSCs are probably used to cure bone injury and other woundings in the near future. Here we will introduce the recent developments in understanding the mechanism of MSCs action in bone regeneration and repairing.
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Affiliation(s)
- Jin Shao
- Department of Orthopaedics, Shanghai Pudong New Area Gongli Hospital, Second Military Medical University, Shanghai, 200135, China.
| | - Weiwei Zhang
- State Key Laboratory of Oncogenes and Related Genes, Renji-Med X Clinical Stem Cell Research Center, Ren Ji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, 200127, China.
| | - Tieyi Yang
- Department of Orthopaedics, Shanghai Pudong New Area Gongli Hospital, Second Military Medical University, Shanghai, 200135, China.
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11
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Nowakowski A, Walczak P, Janowski M, Lukomska B. Genetic Engineering of Mesenchymal Stem Cells for Regenerative Medicine. Stem Cells Dev 2015; 24:2219-42. [PMID: 26140302 DOI: 10.1089/scd.2015.0062] [Citation(s) in RCA: 26] [Impact Index Per Article: 2.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/13/2022] Open
Abstract
Mesenchymal stem cells (MSCs), which can be obtained from various organs and easily propagated in vitro, are one of the most extensively used types of stem cells and have been shown to be efficacious in a broad set of diseases. The unique and highly desirable properties of MSCs include high migratory capacities toward injured areas, immunomodulatory features, and the natural ability to differentiate into connective tissue phenotypes. These phenotypes include bone and cartilage, and these properties predispose MSCs to be therapeutically useful. In addition, MSCs elicit their therapeutic effects by paracrine actions, in which the metabolism of target tissues is modulated. Genetic engineering methods can greatly amplify these properties and broaden the therapeutic capabilities of MSCs, including transdifferentiation toward diverse cell lineages. However, cell engineering can also affect safety and increase the cost of therapy based on MSCs; thus, the advantages and disadvantages of these procedures should be discussed. In this review, the latest applications of genetic engineering methods for MSCs with regenerative medicine purposes are presented.
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Affiliation(s)
- Adam Nowakowski
- 1 NeuroRepair Department, Mossakowski Medical Research Centre, Polish Academy of Sciences , Warsaw, Poland
| | - Piotr Walczak
- 2 Division of Magnetic Resonance Research, Russell H. Morgan Department of Radiology and Radiological Science, The Johns Hopkins University School of Medicine , Baltimore, Maryland.,3 Cellular Imaging Section and Vascular Biology Program, Institute for Cell Engineering, The Johns Hopkins University School of Medicine , Baltimore, Maryland.,4 Department of Radiology, Faculty of Medical Sciences, University of Warmia and Mazury , Olsztyn, Poland
| | - Miroslaw Janowski
- 1 NeuroRepair Department, Mossakowski Medical Research Centre, Polish Academy of Sciences , Warsaw, Poland .,2 Division of Magnetic Resonance Research, Russell H. Morgan Department of Radiology and Radiological Science, The Johns Hopkins University School of Medicine , Baltimore, Maryland.,3 Cellular Imaging Section and Vascular Biology Program, Institute for Cell Engineering, The Johns Hopkins University School of Medicine , Baltimore, Maryland
| | - Barbara Lukomska
- 1 NeuroRepair Department, Mossakowski Medical Research Centre, Polish Academy of Sciences , Warsaw, Poland
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Modulation of Hyaluronan Synthesis by the Interaction between Mesenchymal Stem Cells and Osteoarthritic Chondrocytes. Stem Cells Int 2015; 2015:640218. [PMID: 26273306 PMCID: PMC4529975 DOI: 10.1155/2015/640218] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/13/2014] [Revised: 12/11/2014] [Accepted: 01/02/2015] [Indexed: 12/27/2022] Open
Abstract
Bone marrow mesenchymal stem cells (BM-MSCs) are considered a good source for cellular therapy in cartilage repair. But, their potential to repair the extracellular matrix, in an osteoarthritic environment, is still controversial. In osteoarthritis (OA), anti-inflammatory action and extracellular matrix production are important steps for cartilage healing. This study examined the interaction of BM-MSC and OA-chondrocyte on the production of hyaluronan and inflammatory cytokines in a Transwell system. We compared cocultured BM-MSCs and OA-chondrocytes with the individually cultured controls (monocultures). There was a decrease in BM-MSCs cell count in coculture with OA-chondrocytes when compared to BM-MSCs alone. In monoculture, BM-MSCs produced higher amounts of hyaluronan than OA-chondrocytes and coculture of BM-MSCs with OA-chondrocytes increased hyaluronan production per cell. Hyaluronan synthase-1 mRNA expression was upregulated in BM-MSCs after coculture with OA-chondrocytes, whereas hyaluronidase-1 was downregulated. After coculture, lower IL-6 levels were detected in BM-MSCs compared with OA-chondrocytes. These results indicate that, in response to coculture with OA-chondrocytes, BM-MSCs change their behavior by increasing production of hyaluronan and decreasing inflammatory cytokines. Our results indicate that BM-MSCs per se could be a potential tool for OA regenerative therapy, exerting short-term effects on the local microenvironment even when cell:cell contact is not occurring.
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Uth K, Trifonov D. Stem cell application for osteoarthritis in the knee joint: A minireview. World J Stem Cells 2014; 6:629-636. [PMID: 25426260 PMCID: PMC4178263 DOI: 10.4252/wjsc.v6.i5.629] [Citation(s) in RCA: 30] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/27/2014] [Revised: 08/31/2014] [Accepted: 09/17/2014] [Indexed: 02/06/2023] Open
Abstract
Knee osteoarthritis is a chronic, indolent disease that will affect an ever increasing number of patients, especially the elderly and the obese. It is characterized by degeneration of the cartilage substance inside the knee which leads to pain, stiffness and tenderness. By some estimations in 2030, only in the United States, this medical condition will burden 67 million people. While conventional treatments like physiotherapy or drugs offer temporary relief of clinical symptoms, restoration of normal cartilage function has been difficult to achieve. Moreover, in severe cases of knee osteoarthritis total knee replacement may be required. Total knee replacements come together with high effort and costs and are not always successful. The aim of this review is to outline the latest advances in stem cell therapy for knee osteoarthritis as well as highlight some of the advantages of stem cell therapy over traditional approaches aimed at restoration of cartilage function in the knee. In addition to the latest advances in the field, challenges associated with stem cell therapy regarding knee cartilage regeneration and chondrogenesis in vitro and in vivo are also outlined and analyzed. Furthermore, based on their critical assessment of the present academic literature the authors of this review share their vision about the future of stem cell applications in the treatment of knee osteoarthritis.
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