scholarly journals Derivation of Isogenic Mesodermal and Ectomesodermal Chondrocytes from Human Induced Pluripotent Stem Cells for Articular Cartilage Regeneration

2020 ◽  
Author(s):  
Ming-Song Lee ◽  
Matthew J. Stebbins ◽  
Hongli Jiao ◽  
Hui-Ching Huang ◽  
Brian E. Walzack ◽  
...  

AbstractGenerating phenotypic chondrocytes from human pluripotent stem cells through driving developmental lineage-specific differentiation remains to be of great interest in the field of cartilage regeneration. In this study, we derived chondrocytes from human induced pluripotent stem cells (hiPSCs) along the mesodermal or ectomesodermal lineages to prepare isogenic mesodermal cell-derived chondrocytes (MC-Chs) or neural crest cell-derived chondrocytes (NCC-Chs), respectively, and further evaluated differences in their cellular and molecular characteristics and cartilage repair capabilities. Our results showed that both lineage-derived chondrocytes expressed hyaline cartilage-associated markers and were capable of forming hyaline cartilage-like tissue ectopically and at joint defects. Moreover, NCC-Chs showed the absence of markers of hypertrophic chondrocytes and revealed a closer morphological resemblance to articular chondrocytes and a greater capability of producing glycosaminoglycans and collagen type 2 at cartilage defects compared to MC-Chs. It was found that the profile of global transcript expression of NCC-Chs more closely resembled that of native chondrocytes (NCs) than that of MC-Chs. Induced by additional growth factors identified through the analysis of transcriptome comparison to NCs, both MC-Chs and NCC-Chs showed a further increase in the phenotype of hyaline cartilage chondrocytes. Results of this study reveal differences in cellular and molecular characteristics and cartilage repair capabilities between isogenic hiPSC-derived MC-Chs and NCC-Chs and demonstrate that chondrocytes derived from hiPSCs along the ectomesodermal lineage are a potential cell source for articular cartilage regeneration.

2017 ◽  
Vol 2017 ◽  
pp. 1-7 ◽  
Author(s):  
Shinji Kotaka ◽  
Shigeyuki Wakitani ◽  
Akira Shimamoto ◽  
Naosuke Kamei ◽  
Mikiya Sawa ◽  
...  

Cartilage regeneration treatments using stem cells are associated with problems due to the cell source and the difficulty of delivering the cells to the cartilage defect. We consider labeled induced pluripotent stem (iPS) cells to be an ideal source of cells for tissue regeneration, and if iPS cells could be delivered only into cartilage defects, it would be possible to repair articular cartilage. Consequently, we investigated the effect of magnetically labeled iPS (m-iPS) cells delivered into an osteochondral defect by magnetic field on the repair of articular cartilage. iPS cells were labeled magnetically and assessed for maintenance of pluripotency by their ability to form embryoid bodies in vitro and to form teratomas when injected subcutaneously into nude rats. These cells were delivered specifically into cartilage defects in nude rats using a magnetic field. The samples were graded according to the histologic grading score for cartilage regeneration. m-iPS cells differentiated into three embryonic germ layers and formed teratomas in the subcutaneous tissue. The histologic grading score was significantly better in the treatment group compared to the control group. m-iPS cells maintained pluripotency, and the magnetic delivery system proved useful and safe for cartilage repair using iPS cells.


2018 ◽  
Vol 28 (5) ◽  
pp. 529-537 ◽  
Author(s):  
Yeri Alice Rim ◽  
Yoojun Nam ◽  
Ji Hyeon Ju

Regeneration of articular cartilage is of great interest in cartilage tissue engineering since articular cartilage has a low regenerative capacity. Due to the difficulty in obtaining healthy cartilage for transplantation, there is a need to develop an alternative and effective regeneration therapy to treat degenerative or damaged joint diseases. Stem cells including various adult stem cells and pluripotent stem cells are now actively used in tissue engineering. Here, we provide an overview of the current status of cord blood cells and induced pluripotent stem cells derived from these cells in cartilage regeneration. The abilities of these cells to undergo chondrogenic differentiation are also described. Finally, the technical challenges of articular cartilage regeneration and future directions are discussed.


2013 ◽  
Vol 34 (6) ◽  
pp. 281-288 ◽  
Author(s):  
Sakura UTO ◽  
Satoru NISHIZAWA ◽  
Yutaka TAKASAWA ◽  
Yukiyo ASAWA ◽  
Yuko FUJIHARA ◽  
...  

2021 ◽  
Vol 7 (21) ◽  
pp. eabf0907
Author(s):  
Ming-Song Lee ◽  
Matthew J. Stebbins ◽  
Hongli Jiao ◽  
Hui-Ching Huang ◽  
Ellen M. Leiferman ◽  
...  

Generating phenotypic chondrocytes from pluripotent stem cells is of great interest in the field of cartilage regeneration. In this study, we differentiated human induced pluripotent stem cells into the mesodermal and ectomesodermal lineages to prepare isogenic mesodermal cell–derived chondrocytes (MC-Chs) and neural crest cell–derived chondrocytes (NCC-Chs), respectively, for comparative evaluation. Our results showed that both MC-Chs and NCC-Chs expressed hyaline cartilage–associated markers and were capable of generating hyaline cartilage–like tissue ectopically and at joint defects. Moreover, NCC-Chs revealed closer morphological and transcriptional similarities to native articular chondrocytes than MC-Chs. NCC-Ch implants induced by our growth factor mixture demonstrated increased matrix production and stiffness compared to MC-Ch implants. Our findings address how chondrocytes derived from pluripotent stem cells through mesodermal and ectomesodermal differentiation are different in activities and functions, providing the crucial information that helps make appropriate cell choices for effective regeneration of articular cartilage.


2021 ◽  
Vol 6 (1) ◽  
Author(s):  
Kangkang Zha ◽  
Xu Li ◽  
Zhen Yang ◽  
Guangzhao Tian ◽  
Zhiqiang Sun ◽  
...  

AbstractArticular cartilage is susceptible to damage but hard to self-repair due to its avascular nature. Traditional treatment methods are not able to produce satisfactory effects. Mesenchymal stem cells (MSCs) have shown great promise in cartilage repair. However, the therapeutic effect of MSCs is often unstable partly due to their heterogeneity. Understanding the heterogeneity of MSCs and the potential of different types of MSCs for cartilage regeneration will facilitate the selection of superior MSCs for treating cartilage damage. This review provides an overview of the heterogeneity of MSCs at the donor, tissue source and cell immunophenotype levels, including their cytological properties, such as their ability for proliferation, chondrogenic differentiation and immunoregulation, as well as their current applications in cartilage regeneration. This information will improve the precision of MSC-based therapeutic strategies, thus maximizing the efficiency of articular cartilage repair.


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