SOX-6, 9-Transfected Adipose Stem Cells to Treat Surgically-Induced Osteoarthritis in Goats

Ko, Ji‐Yun; Lee, Jimin; Lee, Jung Sun; Ryu, Yang-Hwan; Im, Gun‐Il

doi:10.1089/ten.tea.2018.0189

Cited by 22 publications

(20 citation statements)

References 38 publications

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“…In vivo tracking of injected SOX ‐ 6 , 9 ASCs in rats demonstrated that these cells disappeared from the joint cavity within 2 weeks, suggesting a paracrine mode of action. In a surgically induced goat model of OA, IA SOX ‐ 6 , 9 ASCs at a dose of 0.6 × 10 7 best preserved AC and produced significantly better macroscopic and microscopic scores than negative controls in femoral and tibial articular surfaces …”

Section: Gene‐enhanced Cartilage Regenerationmentioning

confidence: 97%

“…Quality control issues that inevitably follow cell therapeutics can be made more complicated with the addition of genes to cells. Also, IA injected cells were shown to undergo death within a short period of time (2–3 weeks) without engraftment into cartilage defects . In those circumstances, a brief paracrine effect before cell death will be all that can be expected from a gene‐cell therapeutics.…”

Section: Summary and Future Perspectivesmentioning

confidence: 99%

“…In a surgically induced goat model of OA, IA SOX-6, 9 ASCs at a dose of 0.6 × 10 7 best preserved AC and produced significantly better macroscopic and microscopic scores than negative controls in femoral and tibial articular surfaces. 57 Reprogramming Direct reprogramming or direct conversion means converting cells into other lineages without undergoing full reprogramming into pluripotent stem cells (PSCs). It has the potential advantage of skipping complicated differentiation processes needed for PSC conversion into the desired lineage.…”

Section: Overexpression Of Transcription Factors (Tfs) For Cartilage mentioning

confidence: 99%

“…Also, IA injected cells were shown to undergo death within a short period of time (2-3 weeks) without engraftment into cartilage defects. 57 In those circumstances, a brief paracrine effect before cell death will be all that can be expected from a gene-cell therapeutics. It should be considered whether gene transfer is still necessary when injected cells survive for such a short period of time and limited effects are expected from the transgene.…”

Section: Summary and Future Perspectivesmentioning

confidence: 99%

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Multi‐Disciplinary Approaches for Cell‐Based Cartilage Regeneration

Johnstone

Stoddart

2019

Journal Orthopaedic Research

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Articular cartilage does not regenerate in adults. A lot of time and resources have been dedicated to cartilage regeneration research. The current understanding suggests that multi‐disciplinary approach including biologic, genetic, and mechanical stimulations may be needed for cell‐based cartilage regeneration. This review summarizes contents of a workshop sponsored by International Combined Orthopaedic Societies during the 2019 annual meeting of the Orthopaedic Research Society held in Austin, Texas. Three approaches for cell‐based cartilage regeneration were introduced, including cellular basis of chondrogenesis, gene‐enhanced cartilage regeneration, and physical modulation to divert stem cells to chondrogenic cell fate. While the complicated nature of cartilage regeneration has not allowed us to achieve successful regeneration of hyaline articular cartilage so far, the utilization of multi‐disciplinary approaches in various fields of biomedical engineering will provide means to achieve this goal faster. © 2019 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 38:463–472, 2020

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Section: Gene‐enhanced Cartilage Regenerationmentioning

confidence: 97%

Section: Summary and Future Perspectivesmentioning

confidence: 99%

Section: Overexpression Of Transcription Factors (Tfs) For Cartilage mentioning

confidence: 99%

Section: Summary and Future Perspectivesmentioning

confidence: 99%

See 2 more Smart Citations

Multi‐Disciplinary Approaches for Cell‐Based Cartilage Regeneration

Johnstone

Stoddart

2019

Journal Orthopaedic Research

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“…Aside from the use of differentiation signaling growth factors, some studies have induced differentiation through overexpression of SOX transcription factors in stem cells, which are known to be heavily involved in chondrogenesis. 126,127 Although SOX9 is known as the main chondrogenic transcription factor, in vivo delivery of cells has involved cells overexpressing both SOX9 and SOX6, as SOX6 enhances SOX9 activity. 128 One of the two studies, referenced in Table 5, uses ANGPTL4 shRNA along with SOX6 and SOX9 overexpression, as ANGPT4 has been shown to be higher in OA chondrocytes and induces MMP expression within them and stem cells.…”

Section: Gene-engineered Stem Cellsmentioning

confidence: 99%

Improving Cell Therapy Survival and Anabolism in Harsh Musculoskeletal Disease Environments

Farhang

Silverman²,

Bowles

2020

Tissue Engineering Part B: Reviews

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Cell therapies are an up and coming technology in orthopedic medicine that has the potential to provide regenerative treatments for musculoskeletal disease. Despite numerous cell therapies showing preclinical success for common musculoskeletal indications of disc degeneration and osteoarthritis, there have been mixed results when testing these therapies in humans during clinical trials. A theory behind the mixed success of these cell therapies is that the harsh microenvironments of the disc and knee they are entering inhibit their anabolism and survival. Therefore, there is much ongoing research looking into how to improve the survival and anabolism of cell therapies within these musculoskeletal disease environments. This includes research into improving cell function under specific microenvironmental conditions known to exist in the intervertebral disc (IVD) and knee environment such as hypoxia, low-nutrient conditions, hyperosmolarity, acidity, and inflammation. This research also includes improving differentiation of cells into desired native cell phenotypes to better enhance their survival and anabolism in the knee and IVD. This review highlights the effects of specific musculoskeletal microenvironmental challenges on cell therapies and what research is being done to overcome these challenges.

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Characterization of adipose‐derived stromal/stem cell spheroids versus single‐cell suspension in cell survival and arrest of osteoarthritis progression

Park

Kim

et al. 2020

J Biomedical Materials Res

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The current study evaluated the hypothesis that the administration of spheroidal adipose‐derived stromal/stem cells (ASCs) promotes cell survival and arrests the progression of surgically induced osteoarthritis (OA) in a rat model. We also tested the optimal conditions for spheroid production from ASCs using microwell methods. The formation of ASC spheroids was optimized at a well diameter of 600 μm under cell concentrations of 106cell/ml. When ASC spheroids cultured in 3D were compared with ASCs cultured in 2D monolayer, the cell survival and chondrogenic potential were enhanced while the apoptosis was reduced in ASC spheroids compared with ASCs in 2D monolayer culture. In vivo tracking of fluorescently labeled ASCs in the knee joints of rats with surgically induced OA showed longer fluorescent activity at a higher intensity in ASC spheroids than in ASC single‐cell suspension. When OA‐induced rats treated with ASC injection were sacrificed after 8 weeks, the OARSI score was enhanced in both ASC single‐cell suspension and ASC spheroids compared with negative control, spheroid treatment resulting in a better score than single‐cell treatment. However, injected cells were not detectable from the joints. These finding altogether suggests that ASC spheroids have better in vitro and in vivo survival and chondrogenic potential and exert greater regenerative effects for articular cartilage and arrest the progression of surgically induced OA better than ASCs in single‐cell suspension by the paracrine mode of action. The study findings support the notion of developing cell therapeutics to treat OA based on ASC spheroid forms.

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SOX-6, 9-Transfected Adipose Stem Cells to Treat Surgically-Induced Osteoarthritis in Goats

Cited by 22 publications

References 38 publications

Multi‐Disciplinary Approaches for Cell‐Based Cartilage Regeneration

Multi‐Disciplinary Approaches for Cell‐Based Cartilage Regeneration

Improving Cell Therapy Survival and Anabolism in Harsh Musculoskeletal Disease Environments

Characterization of adipose‐derived stromal/stem cell spheroids versus single‐cell suspension in cell survival and arrest of osteoarthritis progression

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