Stepwise preconditioning enhances mesenchymal stem cell-based cartilage regeneration through epigenetic modification

Lin, Sien; Lee, Wayne; Xu, Liangliang; Wang, Yujia; Chen, Yong; Ho, Kwok W.; Qin, Ling; Jiang, Xiaohua; Cui, Liao; Li, Gang

doi:10.1016/j.joca.2017.05.008

Cited by 21 publications

(17 citation statements)

References 33 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Until now, the etiology and pathophysiology of OA have not been well documented. Various treatments, such as cellular therapies (Fu et al, 2014;Lee and Wang, 2017;Lin et al, 2017;Teo et al, 2019;Xu et al, 2019), administration of certain drugs or chemicals (Zhang et al, 2016(Zhang et al, , 2019Yao et al, 2019), therapeutic surgeries (Chen Y. et al, 2015), and biofabrication approach (Tatman et al, 2015;Onofrillo et al, 2018;Lee et al, 2019), have been intensely studied and tested in various preclinical studies and clinical trials during recent decades (Lee and Wang, 2017;Zhang et al, 2019). However, several hurdles are required to be addressed for therapeutic optimization before clinical translation.…”

Section: Introductionmentioning

confidence: 99%

Molecular Insights Into Lysyl Oxidases in Cartilage Regeneration and Rejuvenation

Lin

2020

Front. Bioeng. Biotechnol.

View full text Add to dashboard Cite

Articular cartilage remains among the most difficult tissues to regenerate due to its poor self-repair capacity. The lysyl oxidase family (LOX; also termed as protein-lysine 6oxidase), mainly consists of lysyl oxidase (LO) and lysyl oxidase-like 1-4 (LOXL1-LOXL4), has been traditionally defined as cuproenzymes that are essential for stabilization of extracellular matrix, particularly cross-linking of collagen and elastin. LOX is essential in the musculoskeletal system, particularly cartilage. LOXs-mediated collagen cross-links are essential for the functional integrity of articular cartilage. Appropriate modulation of the expression or activity of certain LOX members selectively may become potential promising strategy for cartilage repair. In the current review, we summarized the advances of LOX in cartilage homeostasis and functioning, as well as copper-mediated activation of LOX through hypoxia-responsive signaling axis during recent decades. Also, the molecular signaling network governing LOX expression has been summarized, indicating that appropriate modulation of hypoxia-responsive-signaling-directed LOX expression through manipulation of bioavailability of copper and oxygen is promising for further clinical implications of cartilage regeneration, which has emerged as a potential therapeutic approach for cartilage rejuvenation in tissue engineering and regenerative medicine. Therefore, targeted regulation of copper-mediated hypoxiaresponsive signalling axis for selective modulation of LOX expression may become potential effective therapeutics for enhanced cartilage regeneration and rejuvenation in future clinical implications.

show abstract

Section: Introductionmentioning

confidence: 99%

Molecular Insights Into Lysyl Oxidases in Cartilage Regeneration and Rejuvenation

Lin

2020

Front. Bioeng. Biotechnol.

View full text Add to dashboard Cite

show abstract

“…Interestingly, the dedifferentiation-reprogramming method was also effective in chondrogenesis. According to Li et al 129 , rat MSCs in vitro that are incubated in chondrogenic induction medium undergo chondrogenesis and then are allowed to grow and subculture in growth medium to expand and dedifferentiate (Fig. 4b).…”

Section: Dedifferentiation In Diseases (As a Pathological Factor)mentioning

confidence: 99%

“… a Immunofluorescence staining revealed the preferential neuronal differentiation of De-MSCs, as evidenced by the higher expression of neuronal markers, including neurofilament-M (NF-M) and microtubule-associated protein 2 (MAP2) (used with permission from John Wiley and Sons/Hsiao et al 127 ). b Histology and immunohistochemistry revealed that the M-MSC group exhibited a greater therapeutic effect on OA, as evidenced by the increased ECM deposition, increased number of GFP-positive cells, and reduction in MMP-13 expression 129 (Copyright 2017, with permission from Elsevier). …”

Section: Introductionmentioning

confidence: 99%

Dedifferentiation: inspiration for devising engineering strategies for regenerative medicine

Yao

Wang

2020

npj Regen Med

View full text Add to dashboard Cite

Cell dedifferentiation is the process by which cells grow reversely from a partially or terminally differentiated stage to a less differentiated stage within their own lineage. This extraordinary phenomenon, observed in many physiological processes, inspires the possibility of developing new therapeutic approaches to regenerate damaged tissue and organs. Meanwhile, studies also indicate that dedifferentiation can cause pathological changes. In this review, we compile the literature describing recent advances in research on dedifferentiation, with an emphasis on tissue-specific findings, cellular mechanisms, and potential therapeutic applications from an engineering perspective. A critical understanding of such knowledge may provide fresh insights for designing new therapeutic strategies for regenerative medicine based on the principle of cell dedifferentiation.

show abstract

“…These results implied that the regenerated cartilages seem to have a memory of their original form. Although the underlying mechanisms were still unclear, it could be speculated that the epigenetic regulation might play an important role in determining the ultimate fate of regenerated cartilage type (Carlson et al, ; Duan, Liang, Ma, Zhu, & Wang, ; Lin et al, ). Nevertheless, all of the in vivo regenerated cartilage expressed noncartilage‐specific ECM, such as collagen type I, which might be a result of the dedifferentiation status of expanded chondrocytes before used for cartilage regeneration, transforming growth factor‐beta in the culture medium, and the regulation of the subcutaneous micro‐environment.…”

Section: Discussionmentioning

confidence: 99%

Cell yield, chondrogenic potential, and regenerated cartilage type of chondrocytes derived from ear, nasoseptal, and costal cartilage

Xia

Xiao

et al. 2017

J Tissue Eng Regen Med

View full text Add to dashboard Cite

Functional reconstruction of large cartilage defects in subcutaneous sites remains clinically challenging because of limited donor cartilage. Tissue engineering is a promising and widely accepted strategy for cartilage regeneration. To date, however, this strategy has not achieved a significant breakthrough in clinical translation owing to a lack of detailed preclinical data on cell yield and functionality of clinically applicable chondrocytes. To address this issue, the current study investigated the initial cell yield, proliferative potential, chondrogenic capacity, and regenerated cartilage type of human chondrocytes derived from auricular, nasoseptal, and costal cartilage using a scaffold-free cartilage regeneration model (cartilage sheet). Chondrocytes from all sources exhibited high sensitivity to basic fibroblast growth factor within 8 passages. Nasoseptal chondrocytes presented the strongest proliferation rate, whereas auricular chondrocytes obtained the highest total cell amount using comparable cartilage sample weights. Importantly, all chondrocytes at fifth passage showed strong chondrogenic capacity both in vitro and in the subcutaneous environment of nude mice. Although some significant differences in histological structure, cartilage matrix content and cartilage type specific proteins were observed between the in vitro engineered cartilage and original tissue; the in vivo regenerated cartilage showed mature cartilage features with high similarity to their original native tissue, except for minor matrix changes influenced by the in vivo environment. The current study provides detailed preclinical data for choice of chondrocyte source and thus promotes the clinical translation of cartilage regeneration approach.

show abstract

Stepwise preconditioning enhances mesenchymal stem cell-based cartilage regeneration through epigenetic modification

Abstract: These findings indicated a feasible method to obtain a cell population with high survivability and chondrogenic commitment for the treatment of OA.

Cited by 21 publications

References 33 publications

Molecular Insights Into Lysyl Oxidases in Cartilage Regeneration and Rejuvenation

Molecular Insights Into Lysyl Oxidases in Cartilage Regeneration and Rejuvenation

Dedifferentiation: inspiration for devising engineering strategies for regenerative medicine

Cell yield, chondrogenic potential, and regenerated cartilage type of chondrocytes derived from ear, nasoseptal, and costal cartilage

Contact Info

Product

Resources

About