Harnessing knee joint resident mesenchymal stem cells in cartilage tissue engineering

Xu, Xiao Gang; Xu, Limei; Xia, Jiang; Wen, Caining; Liang, Yujie; Zhang, Yuanmin

doi:10.1016/j.actbio.2023.07.024

Cited by 33 publications

(12 citation statements)

References 203 publications

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“…The mesenchymal stem cells-derived sEVs showed promising potential for novel treatments of osteoarthritis, given their high biocompatibility, low immunogenicity, and better ability to cross biological barriers compared to MSCs 43 . Infrapatellar fat pad (IPFP)-derived MSCs promoted the proliferation of chondrocytes and synthesis of extracellular matrix and reduced expression of catabolic factors to prevent cartilage damage and relieve walking disability 44 .…”

Section: Discussionmentioning

confidence: 99%

Small extracellular vesicles (sEVs)-based gene delivery platform for cell-specific CRISPR/Cas9 genome editing

Dubey,

Chen,

Jiang

et al. 2024

Theranostics

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Small extracellular vesicles (sEVs) are naturally occurring vesicles that have the potential to be manipulated to become promising drug delivery vehicles for on-demand in vitro and in vivo gene editing. Here, we developed the modular safeEXO platform, a prototype sEV delivery vehicle that is mostly devoid of endogenous RNA and can efficaciously deliver RNA and ribonucleoprotein (RNP) complexes to their intended intracellular targets manifested by downstream biologic activity. We also successfully engineered producer cells to produce safeEXO vehicles that contain endogenous Cas9 (safeEXO-CAS) to effectively deliver efficient ribonucleoprotein (RNP)-mediated CRISPR genome editing machinery to organs or diseased cells in vitro and in vivo . We confirmed that safeEXO-CAS sEVs could co-deliver ssDNA, sgRNA and siRNA, and efficaciously mediate gene insertion in a dose-dependent manner. We demonstrated the potential to target safeEXO-CAS sEVs by engineering sEVs to express a tissue-specific moiety, integrin alpha-6 (safeEXO-CAS-ITGA6), which increased their uptake to lung epithelial cells in vitro and in vivo . We tested the ability of safeEXO-CAS-ITGA6 loaded with EMX1 sgRNAs to induce lung-targeted editing in mice, which demonstrated significant gene editing in the lungs with no signs of morbidity or detectable changes in immune cell populations. Our results demonstrate that our modular safeEXO platform represents a targetable, safe, and efficacious vehicle to deliver nucleic acid-based therapeutics that successfully reach their intracellular targets. Furthermore, safeEXO producer cells can be genetically manipulated to produce safeEXO vehicles containing CRISPR machinery for more efficient RNP-mediated genome editing. This platform has the potential to improve current therapies and increase the landscape of treatment for various human diseases using RNAi and CRISPR approaches.

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Section: Discussionmentioning

confidence: 99%

Small extracellular vesicles (sEVs)-based gene delivery platform for cell-specific CRISPR/Cas9 genome editing

Dubey,

Chen,

Jiang

et al. 2024

Theranostics

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“…EVs derived from mesenchymal stem cells (MSC) are also widely used in gene therapy. 90 Wang et al investigated the effects of small-molecule modulators on the secretion of EVs in MSC, and found that the combination of N-methyldopamine and norepinephrine increased the production of EVs by three folds. 91 However, the introduction of exogenous drugs into cells may induce chemical and physical damages to proteins and alter the biophysical properties of EVs, including their size, loading capacity, molecular content and cytotoxicity.…”

Section: Generation Isolation and Purification Of Evsmentioning

confidence: 99%

Extracellular Vesicles: A New Star for Gene Drug Delivery

Sun,

Zhang,

Liu

et al. 2024

IJN

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Recently, gene therapy has become a subject of considerable research and has been widely evaluated in various disease models. Though it is considered as a stand-alone agent for COVID-19 vaccination, gene therapy is still suffering from the following drawbacks during its translation from the bench to the bedside: the high sensitivity of exogenous nucleic acids to enzymatic degradation; the severe side effects induced either by exogenous nucleic acids or components in the formulation; and the difficulty to cross the barriers before reaching the therapeutic target. Therefore, for the successful application of gene therapy, a safe and reliable transport vector is urgently needed. Extracellular vesicles (EVs) are the ideal candidate for the delivery of gene drugs owing to their low immunogenicity, good biocompatibility and low toxicity. To better understand the properties of EVs and their advantages as gene drug delivery vehicles, this review covers from the origin of EVs to the methods of EVs generation, as well as the common methods of isolation and purification in research, with their pros and cons discussed. Meanwhile, the engineering of EVs for gene drugs is also highlighted. In addition, this paper also presents the progress in the EVs-mediated delivery of microRNAs, small interfering RNAs, messenger RNAs, plasmids, and antisense oligonucleotides. We believe this review will provide a theoretical basis for the development of gene drugs.

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“…We counsel these patients that at present there are no clinically available injection treatments which can recreate their native cartilage and, although at times various biologic treatments are referred to as stem cell treatments, the currently available treatments (PRP, bone marrow aspirate, adipose preparations) contain such low concentrations of stem cells that the practice of referring to them in this manner at all has been discouraged. This point notwithstanding, there is great interest in harnessing the potential of stem cells [ 44 ]. This includes utilizing them as cell based therapies or as similarly derived exosomes with signaling factors to halt the progression of degeneration and even potentially reverse it [ 45 , 46 , 47 , 48 , 49 , 50 ].…”

Section: Non-surgical Managementmentioning

confidence: 99%

Knee Joint Preservation in Tactical Athletes: A Comprehensive Approach Based upon Lesion Location and Restoration of the Osteochondral Unit

Cognetti,

Defoor,

Yuan

et al. 2024

Bioengineering

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The unique physical demands of tactical athletes put immense stress on the knee joint, making these individuals susceptible to injury. In order to ensure operational readiness, management options must restore and preserve the native architecture and minimize downtime, while optimizing functionality. Osteochondral lesions (OCL) of the knee have long been acknowledged as significant sources of knee pain and functional deficits. The management of OCL is predicated on certain injury characteristics, including lesion location and the extent of subchondral disease. Techniques such as marrow stimulation, allograft and autologous chondrocyte implantation are examined in detail, with a focus on their application and suitability in tactical athlete populations. Moreover, the restoration of the osteochondral unit (OCU) is highlighted as a central aspect of knee joint preservation. The discussion encompasses the biomechanical considerations and outcomes associated with various cartilage restoration techniques. Factors influencing procedure selection, including lesion size, location, and patient-specific variables, are thoroughly examined. Additionally, the review underscores the critical role of post-operative rehabilitation and conditioning programs in optimizing outcomes. Strengthening the surrounding musculature, enhancing joint stability, and refining movement patterns are paramount in facilitating the successful integration of preservation procedures. This narrative review aims to provide a comprehensive resource for surgeons, engineers, and sports medicine practitioners engaged in the care of tactical athletes and the field of cartilage restoration. The integration of advanced preservation techniques and tailored rehabilitation protocols offers a promising avenue for sustaining knee joint health and function in this demanding population.

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Harnessing knee joint resident mesenchymal stem cells in cartilage tissue engineering

Cited by 33 publications

References 203 publications

Small extracellular vesicles (sEVs)-based gene delivery platform for cell-specific CRISPR/Cas9 genome editing

Small extracellular vesicles (sEVs)-based gene delivery platform for cell-specific CRISPR/Cas9 genome editing

Extracellular Vesicles: A New Star for Gene Drug Delivery

Knee Joint Preservation in Tactical Athletes: A Comprehensive Approach Based upon Lesion Location and Restoration of the Osteochondral Unit

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