Role of dexamethasone in the long‐term functional maturation of MSC‐laden hyaluronic acid hydrogels for cartilage tissue engineering

Kim, Minwook; Garrity, Sean T.; Steinberg, David R.; Dodge, George R.; Mauck, Robert L.

doi:10.1002/jor.23815

Cited by 7 publications

(8 citation statements)

References 48 publications

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“…It will also be important to assess the role of EVs in an in vivo scenario. Here, we used a chemically defined medium that provides a supportive growth environment, but "conflict" signals in the native joint environment may pose additional challenges (39). Our data support that DP AMSCs have higher expression of antiinflammatory/apoptotic and proliferation/mitosis-related factors (SI Appendix, Tables S1-S11), and therefore EV-mediated factors may help in the transition MSC-based cartilage to the in vivo space.…”

Section: Discussionsupporting

confidence: 54%

“…MSCs were isolated from juvenile (JMSC) or adult (AMSC) bone marrow as described previously (6). These zonal CHs and MSCs were separately maintained in serum-containing medium (10% FBS) (39). Cells of both types were expanded in culture through passage 3.…”

Section: Methodsmentioning

confidence: 99%

“…Cylindrical cores (Ø4 mm × 2.25 mm) were removed from the resulting HA gel sheets using a sterile biopsy punch. These constructs were then cultured in chemically defined media (CM) with 10 ng/mL TGF-β3 (CM+; R&D Systems) (39). Media was changed thrice weekly for up to 8 wk.…”

Section: Methodsmentioning

confidence: 99%

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Extracellular vesicles mediate improved functional outcomes in engineered cartilage produced from MSC/chondrocyte cocultures

Kim

Steinberg

Burdick

et al. 2019

Proc. Natl. Acad. Sci. U.S.A.

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Several recent studies have demonstrated that coculture of chondrocytes (CHs) with bone marrow-derived mesenchymal stem cells (MSCs) improves their chondrogenesis. This implies that intercellular communication dictates fate decisions in recipient cells and/or reprograms their metabolic state to support a differentiated function. While this coculture phenomenon is compelling, the differential chondroinductivity of zonal CHs on MSC cocultures, the nature of the molecular cargo, and their transport mechanisms remains undetermined. Here, we demonstrate that juvenile CHs in coculture with adult MSCs promote functional differentiation and improved matrix production. We further demonstrate that close proximity between the two cell types is a prerequisite for this response and that the outcome of this interaction improves viability, chondrogenesis, matrix formation, and homeostasis in the recipient MSCs. Furthermore, we visualized the transfer of intracellular contents from CHs to nearby MSCs and showed that inhibition of extracellular vesicle (EV) transfer blocks the synergistic effect of coculture, identifying EVs as the primary mode of communication in these cocultures. These findings will forward the development of therapeutic agents and more effective delivery systems to promote cartilage repair.

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Section: Discussionsupporting

confidence: 54%

Section: Methodsmentioning

confidence: 99%

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Extracellular vesicles mediate improved functional outcomes in engineered cartilage produced from MSC/chondrocyte cocultures

Kim

Steinberg

Burdick

et al. 2019

Proc. Natl. Acad. Sci. U.S.A.

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“…Dexamethasone is usually used as a supplement of TGF or BMP to further promote cell proliferation and maximize chondrogenesis or osteogenic induction, so as to achieve optimal chondrogenesis or osteogenic effect. [80]…”

Section: Dexamethasonementioning

confidence: 99%

The role of growth factor in the repair of articular cartilage

Chai

et al. 2019

Preprint

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Background: Natural degeneration or trauma of articular cartilage all can lead to its structural and functional damage. Because of its lack of blood supply and innervation, it has low metabolic activity and difficulty in self-repair after injury. Growth factors provide a new direction for the repair of articular cartilage damage and play an important role. This article will systematically summarize the research progress of traditional growth factors, mainly introduce the newly found growth factors and other synthetic compounds and inorganic particles that can induce stem cells to differentiate into cartilage.Methods: English literatures published in PubMed and SCI databases from August 2000 to August 2019 were searched, Review the relevant literature, The two authors evaluated and screened the quality of the literatures respectively, and senior authors further evaluated them to resolve the disagreement on the inclusion of literatures.Results: Growth factors can significantly promote stem cell proliferation and differentiation. A variety of growth factors can exert synergistically to promote the differentiation of stem cells into cartilage, so as to promote the regeneration of cartilage tissue and repair the damage of articular cartilage. Traditional growth factors that promote articular cartilage repair are bone morphogenetic proteins, cartilage derived morphogenetic protein, transcription growth factor β, fibroblast growth factors and insulin⁃like growth factors. Recent studies have found that kartogenin, platelet-rich plasma, platelet-rich fibrin, force growth factor, etc. can also effectively induce stem cells to differentiate into cartilage and maintain chondrocyte phenotype, synthetic compounds such as dexamethasone and some inorganic particles also promote chondrogenic differentiation.Conclusions: The newly discovered growth factors promote the development of articular cartilage repair, but its mechanism of action is not clear. There are no in vivo experimental studies on dexamethasone and inorganic particles, and its repairing effect and safety are for further study. The synergistic or antagonistic effects between different growth factors, the optimal concentration ratio, and the differences in in vivo and in vitro roles need further study. At present, the research on growth factors mostly stays at the basic stage, and there are few clinical studies, which will be an important direction for further research.

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“…This could include mild hypothermia, serum starvation, hypoxic culture or other strategies that are applied for a period of time prior to implantation . The design of engineered discs could also be modified to include material inclusions that provide the sustained release of small molecules (ie, IL‐1Ra, dexamethasone, glucose, TGF‐β) from within the construct to mitigate the inflammatory and nutrient‐poor environment of the degenerative spine and assist in maintaining engineered disc phenotype …”

Section: Challenges For In Vivo Translation Of An Engineered Discmentioning

confidence: 99%

Promise, progress, and problems in whole disc tissue engineering

Gullbrand

Smith

et al. 2018

JOR Spine

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Intervertebral disc degeneration is frequently implicated as a cause of back and neck pain, which are pervasive musculoskeletal complaints in modern society. For the treatment of end stage disc degeneration, replacement of the disc with a viable, tissue-engineered construct that mimics native disc structure and function is a promising alternative to fusion or mechanical arthroplasty techniques. Substantial progress has been made in the field of whole disc tissue engineering over the past decade, with a variety of innovative designs characterized both in vitro and in vivo in animal models. However, significant barriers to clinical translation remain, including construct size, cell source, culture technique, and the identification of appropriate animal models for preclinical evaluation. Here we review the clinical need for disc tissue engineering, the current state of the field, and the outstanding challenges that will need to be addressed by future work in this area. K E Y W O R D Sanimal models, biomaterials, biomechanics, disc degeneration, mesenchymal stem cells | INTRODUCTIONBack and neck pain place a significant social and economic burden on modern society, affecting nearly 1 in 2 individuals annually. In the United States alone, these conditions are associated with an estimated $194 billion in yearly medical costs and lost wages. Back pain is commonly associated with degenerative disc disease, a progressive condition with complex underlying etiology, during which component tissues undergo an array of cellular and structural changes that ultimately compromises biomechanical function.Although the pathological manifestations of disc degeneration are well characterized, the underlying causes and the origins of discogenic pain are still not well understood, impeding the development of effective therapies. Current treatments for disc degeneration do not restore native disc structure and function, and thus exhibit limited long-term efficacy. Tissue engineering offers the promise of generating de novo, living structures that recapitulate the form, function, and biology of healthy host tissues with the potential to treat a variety musculoskeletal disorders, including disc degeneration. Here, we review recent progress in the field of whole disc tissue engineering as well as the barriers that will need to be addressed for the successful clinical translation of engineered discs. | INTERVERTEBRAL DISC STRUCTURE AND MECHANICAL FUNCTIONThe intervertebral discs of the spine are composite structures composed of the central nucleus pulposus (NP), the peripheral annulus fibrosus (AF), and the superior and inferior cartilaginous end plates.The extracellular matrix (ECM) of the NP is composed primarily of proteoglycans and type II collagen; the high proteoglycan content of | INTERVERTEBRAL DISC DEGENERATION AND TREATMENTDegeneration of the intervertebral discs may occur with aging or following injury. While the exact pathophysiology of disc degeneration remains unclear, it is known to involve a progressive cascade of cellular,...

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Role of dexamethasone in the long‐term functional maturation of MSC‐laden hyaluronic acid hydrogels for cartilage tissue engineering

Cited by 7 publications

References 48 publications

Extracellular vesicles mediate improved functional outcomes in engineered cartilage produced from MSC/chondrocyte cocultures

Extracellular vesicles mediate improved functional outcomes in engineered cartilage produced from MSC/chondrocyte cocultures

The role of growth factor in the repair of articular cartilage

Promise, progress, and problems in whole disc tissue engineering

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