scholarly journals Recent Developed Strategies for Enhancing Chondrogenic Differentiation of MSC: Impact on MSC-Based Therapy for Cartilage Regeneration

2021 ◽  
Vol 2021 ◽  
pp. 1-15
Author(s):  
Kangkang Zha ◽  
Zhiqiang Sun ◽  
Yu Yang ◽  
Mingxue Chen ◽  
Cangjiang Gao ◽  
...  

Articular cartilage is susceptible to damage, but its self-repair is hindered by its avascular nature. Traditional treatment methods are not able to achieve satisfactory repair effects, and the development of tissue engineering techniques has shed new light on cartilage regeneration. Mesenchymal stem cells (MSCs) are one of the most commonly used seed cells in cartilage tissue engineering. However, MSCs tend to lose their multipotency, and the composition and structure of cartilage-like tissues formed by MSCs are far from those of native cartilage. Thus, there is an urgent need to develop strategies that promote MSC chondrogenic differentiation to give rise to durable and phenotypically correct regenerated cartilage. This review provides an overview of recent advances in enhancement strategies for MSC chondrogenic differentiation, including optimization of bioactive factors, culture conditions, cell type selection, coculture, gene editing, scaffolds, and physical stimulation. This review will aid the further understanding of the MSC chondrogenic differentiation process and enable improvement of MSC-based cartilage tissue engineering.

Biomedicines ◽  
2021 ◽  
Vol 9 (7) ◽  
pp. 714
Author(s):  
Alvin Kai-Xing Lee ◽  
Yen-Hong Lin ◽  
Chun-Hao Tsai ◽  
Wan-Ting Chang ◽  
Tsung-Li Lin ◽  
...  

Cartilage injury is the main cause of disability in the United States, and it has been projected that cartilage injury caused by osteoarthritis will affect 30% of the entire United States population by the year 2030. In this study, we modified hyaluronic acid (HA) with γ-poly(glutamic) acid (γ-PGA), both of which are common biomaterials used in cartilage engineering, in an attempt to evaluate them for their potential in promoting cartilage regeneration. As seen from the results, γ-PGA-GMA and HA, with glycidyl methacrylate (GMA) as the photo-crosslinker, could be successfully fabricated while retaining the structural characteristics of γ-PGA and HA. In addition, the storage moduli and loss moduli of the hydrogels were consistent throughout the curing durations. However, it was noted that the modification enhanced the mechanical properties, the swelling equilibrium rate, and cellular proliferation, and significantly improved secretion of cartilage regeneration-related proteins such as glycosaminoglycan (GAG) and type II collagen (Col II). The cartilage tissue proof with Alcian blue further demonstrated that the modification of γ-PGA with HA exhibited suitability for cartilage tissue regeneration and displayed potential for future cartilage tissue engineering applications. This study built on the previous works involving HA and further showed that there are unlimited ways to modify various biomaterials in order to further bring cartilage tissue engineering to the next level.


2021 ◽  
Author(s):  
Anggraini Barlian ◽  
Dinda Hani’ah Arum Saputri ◽  
Adriel Hernando ◽  
Ekavianty Prajatelistia ◽  
Hutomo Tanoto

Abstract Cartilage tissue engineering, particularly micropattern, can influence the biophysical properties of mesenchymal stem cells (MSCs) leading to chondrogenesis. In this research, human Wharton’s jelly MSCs (hWJ-MSCs) were grown on a striped micropattern containing spider silk protein (spidroin) from Argiope appensa. This research aims to direct hWJ-MSCs chondrogenesis using micropattern made of spidroin bioink as opposed to fibronectin that often used as the gold standard. Cells were cultured on striped micropattern of 500 µm and 1000 µm width sizes without chondrogenic differentiation medium for 21 days. The immunocytochemistry result showed that spidroin contains RGD sequences and facilitates cell adhesion via integrin β1. Chondrogenesis was observed through the expression of glycosaminoglycan, type II collagen, and SOX9. The result on glycosaminoglycan content proved that 1000 µm was the optimal width to support chondrogenesis. Spidroin micropattern induced significantly higher expression of SOX9 mRNA on day-21 and SOX9 protein was located inside the nucleus starting from day-7. COL2A1 mRNA of spidroin micropattern groups was downregulated on day-21 and collagen type II protein was detected starting from day-14. These results showed that spidroin micropattern enhances chondrogenic markers while maintains long-term upregulation of SOX9, and therefore has the potential as a new method for cartilage tissue engineering.


Polymers ◽  
2021 ◽  
Vol 13 (23) ◽  
pp. 4199
Author(s):  
Mahshid Hafezi ◽  
Saied Nouri Khorasani ◽  
Mohadeseh Zare ◽  
Rasoul Esmaeely Neisiany ◽  
Pooya Davoodi

Cartilage is a tension- and load-bearing tissue and has a limited capacity for intrinsic self-healing. While microfracture and arthroplasty are the conventional methods for cartilage repair, these methods are unable to completely heal the damaged tissue. The need to overcome the restrictions of these therapies for cartilage regeneration has expanded the field of cartilage tissue engineering (CTE), in which novel engineering and biological approaches are introduced to accelerate the development of new biomimetic cartilage to replace the injured tissue. Until now, a wide range of hydrogels and cell sources have been employed for CTE to either recapitulate microenvironmental cues during a new tissue growth or to compel the recovery of cartilaginous structures via manipulating biochemical and biomechanical properties of the original tissue. Towards modifying current cartilage treatments, advanced hydrogels have been designed and synthesized in recent years to improve network crosslinking and self-recovery of implanted scaffolds after damage in vivo. This review focused on the recent advances in CTE, especially self-healing hydrogels. The article firstly presents the cartilage tissue, its defects, and treatments. Subsequently, introduces CTE and summarizes the polymeric hydrogels and their advances. Furthermore, characterizations, the advantages, and disadvantages of advanced hydrogels such as multi-materials, IPNs, nanomaterials, and supramolecular are discussed. Afterward, the self-healing hydrogels in CTE, mechanisms, and the physical and chemical methods for the synthesis of such hydrogels for improving the reformation of CTE are introduced. The article then briefly describes the fabrication methods in CTE. Finally, this review presents a conclusion of prevalent challenges and future outlooks for self-healing hydrogels in CTE applications.


2019 ◽  
Vol 13 (1) ◽  
Author(s):  
Azizeh Rahmani Del Bakhshayesh ◽  
Nahideh Asadi ◽  
Alireza Alihemmati ◽  
Hamid Tayefi Nasrabadi ◽  
Azadeh Montaseri ◽  
...  

Abstract Tissue engineering, as an interdisciplinary approach, is seeking to create tissues with optimal performance for clinical applications. Various factors, including cells, biomaterials, cell or tissue culture conditions and signaling molecules such as growth factors, play a vital role in the engineering of tissues. In vivo microenvironment of cells imposes complex and specific stimuli on the cells, and has a direct effect on cellular behavior, including proliferation, differentiation and extracellular matrix (ECM) assembly. Therefore, to create appropriate tissues, the conditions of the natural environment around the cells should be well imitated. Therefore, researchers are trying to develop biomimetic scaffolds that can produce appropriate cellular responses. To achieve this, we need to know enough about biomimetic materials. Scaffolds made of biomaterials in musculoskeletal tissue engineering should also be multifunctional in order to be able to function better in mechanical properties, cell signaling and cell adhesion. Multiple combinations of different biomaterials are used to improve above-mentioned properties of various biomaterials and to better imitate the natural features of musculoskeletal tissue in the culture medium. These improvements ultimately lead to the creation of replacement structures in the musculoskeletal system, which are closer to natural tissues in terms of appearance and function. The present review article is focused on biocompatible and biomimetic materials, which are used in musculoskeletal tissue engineering, in particular, cartilage tissue engineering.


RSC Advances ◽  
2015 ◽  
Vol 5 (117) ◽  
pp. 96725-96732 ◽  
Author(s):  
Zongliang Wang ◽  
Yu Wang ◽  
Peibiao Zhang ◽  
Xuesi Chen

The electrospun MSM-loaded PLGA mat is a promising candidate for cartilage regeneration.


2020 ◽  
Author(s):  
pengcheng xiao ◽  
Zhenglin Zhu ◽  
Chengcheng Du ◽  
Yongsheng Zeng ◽  
junyi Liao ◽  
...  

Abstract Background: Cartilage injuries pose formidable challenges for effective clinical management. Autologous stem cell-based therapies and transgene-enhanced cartilage tissue engineering may open new avenues for the treatment of cartilage injuries. Bone morphogenetic protein 2 (BMP2) is a promising chondrogenic growth factors for transgene-enhanced cartilage tissue engineering. However the BMP2 is failed to maintain a stable chondrogenic phenotype as it also induces robust endochondral ossification. Recently, human synovial derived mesenchymal stem cells (hSMSCs) arouse interested through the poor differentiation potential into osteogenic lineage. Smad7, a protein to antagonizes TGF-β/BMP signaling pathway has been discovered significant in the endochondral ossification. In the present study ,we further explore the effect of downregulate Smad7 in BMP2-induced chondrogenic differentiation of hSMSCs. Methods: hSMSCs were isolated from synovium of human knee joint through adhesion growth. In vitro and in vivo chondrogenic differentiation models of hSMSCs were constructed . Transgenes of BMP2, silencing Smad7 and Smad7 were expressed by adenoviral vectors. The osteogenic differentiation was detected by alkaline phosphatase staining, alizarin red staining. The chondrogenic differentiation was detected by alcian blue staining. Gene expression was determined by reverse transcription and quantitative real-time PCR (RT-qPCR), Immunofluorescence and immunohistochemistry. The subcutaneous stem cell implantation model was established and evaluated by micro-CT , h&e staining, alcian blue staining and immunohistochemistry assay.Results: Compared to other MSCs, hSMSCs performed less of capability to osteogenic differentiation. But the occurrence of endochondral ossification is still inevasible during BMP2 induced cartilage formation. We found that silencing Smad7 enhanced the BMP2-induced chondrogenic differentiation of hSMSCs in vitro. Also, it leading to much less of hypertrophic differentiation. The subcutaneous stem cells implantation assays demonstrated silencing Smad7 potentiates BMP2-induced cartilage formation and inhibits endochondral ossification. Conclusion: This study strongly suggests that application of hSMSCs , cell scaffolds and silencing Smad7 can potentiate BMP2-induced chondrogenic differentiation and inhibit endochondral ossification. Thus, inhibit the expression of Smad7 in BMP2-induced hSMSCs differentiation may be a new strategy for cartilage tissue engineering.


Osteology ◽  
2021 ◽  
Vol 1 (3) ◽  
pp. 149-174
Author(s):  
Naveen Jeyaraman ◽  
Gollahalli Shivashankar Prajwal ◽  
Madhan Jeyaraman ◽  
Sathish Muthu ◽  
Manish Khanna

The field of tissue engineering has revolutionized the world in organ and tissue regeneration. With the robust research among regenerative medicine experts and researchers, the plausibility of regenerating cartilage has come into the limelight. For cartilage tissue engineering, orthopedic surgeons and orthobiologists use the mesenchymal stromal cells (MSCs) of various origins along with the cytokines, growth factors, and scaffolds. The least utilized MSCs are of dental origin, which are the richest sources of stromal and progenitor cells. There is a paradigm shift towards the utilization of dental source MSCs in chondrogenesis and cartilage regeneration. Dental-derived MSCs possess similar phenotypes and genotypes like other sources of MSCs along with specific markers such as dentin matrix acidic phosphoprotein (DMP) -1, dentin sialophosphoprotein (DSPP), alkaline phosphatase (ALP), osteopontin (OPN), bone sialoprotein (BSP), and STRO-1. Concerning chondrogenicity, there is literature with marginal use of dental-derived MSCs. Various studies provide evidence for in-vitro and in-vivo chondrogenesis by dental-derived MSCs. With such evidence, clinical trials must be taken up to support or refute the evidence for regenerating cartilage tissues by dental-derived MSCs. This article highlights the significance of dental-derived MSCs for cartilage tissue regeneration.


2021 ◽  
Vol 2021 ◽  
pp. 1-13
Author(s):  
Liwei Fu ◽  
Pinxue Li ◽  
Hao Li ◽  
Cangjian Gao ◽  
Zhen Yang ◽  
...  

Tissue engineering (TE) has brought new hope for articular cartilage regeneration, as TE can provide structural and functional substitutes for native tissues. The basic elements of TE involve scaffolds, seeded cells, and biochemical and biomechanical stimuli. However, there are some limitations of TE; what most important is that static cell culture on scaffolds cannot simulate the physiological environment required for the development of natural cartilage. Recently, bioreactors have been used to simulate the physical and mechanical environment during the development of articular cartilage. This review aims to provide an overview of the concepts, categories, and applications of bioreactors for cartilage TE with emphasis on the design of various bioreactor systems.


2020 ◽  
Vol 21 (3) ◽  
pp. 1004 ◽  
Author(s):  
Veronica Zubillaga ◽  
Ana Alonso-Varona ◽  
Susana C. M. Fernandes ◽  
Asier M. Salaberria ◽  
Teodoro Palomares

Articular cartilage degeneration is one of the most common causes of pain and disability in middle-aged and older people. Tissue engineering (TE) has shown great therapeutic promise for this condition. The design of cartilage regeneration constructs must take into account the specific characteristics of the cartilaginous matrix, as well as the avascular nature of cartilage and its cells’ peculiar arrangement in isogenic groups. Keeping these factors in mind, we have designed a 3D porous scaffold based on genipin-crosslinked chitosan/chitin nanocrystals for spheroid chondral differentiation of human adipose tissue-derived mesenchymal stem cells (hASCs) induced in hypoxic conditions. First, we demonstrated that, under low oxygen conditions, the chondrospheroids obtained express cartilage-specific markers including collagen type II (COL2A1) and aggrecan, lacking expression of osteogenic differentiation marker collagen type I (COL1A2). These results were associated with an increased expression of hypoxia-inducible factor 1α, which positively directs COL2A1 and aggrecan expression. Finally, we determined the most suitable chondrogenic differentiation pattern when hASC spheroids were seeded in the 3D porous scaffold under hypoxia and obtained a chondral extracellular matrix with a high sulphated glycosaminoglycan content, which is characteristic of articular cartilage. These findings highlight the potential use of such templates in cartilage tissue engineering.


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