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Culture-expanded articular chondrocytes: a potential cellular therapeutic for osteoarthritis with MSC-like properties

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dc.contributor.authorLiebig, Bethany Ellen, author
dc.contributor.authorGoodrich, Laurie, advisor
dc.contributor.authorKisiday, John, advisor
dc.contributor.authorRegan, Daniel, committee member
dc.contributor.authorSantangelo, Kelly, committee member
dc.contributor.authorMcGilvray, Kirk, committee member
dc.contributor.authorBahney, Chelsea, committee member
dc.date.accessioned2023-01-21T01:24:52Z
dc.date.available2025-01-09T01:24:52Z
dc.date.issued2022
dc.description.abstractOsteoarthritis (OA) is a highly prevalent and debilitating joint disease in horses, dogs, and humans. OA affects more than 303 million people globally with an annual economic loss to Americans approaching $200 billion. It has a considerable impact on the patient, resulting in pain and disability and more than 1 million people undergo knee arthroscopy or joint replacement surgery each year due to end-stage OA in the United States. Therefore, OA therapies that produce lasting symptom- and disease-modifying effects are a medical priority. Mesenchymal stromal cells (MSCs) are considered 'medicinal signaling cells' that have been postulated to treat OA by reducing inflammation and restoring joint function. However, IA injection of MSCs into diseased human or companion animal joints has demonstrated only a modest benefit to date, as symptom-modifying effects are often temporary, and evidence of disease-modification has been minimal. It has been reported that culture-expanded chondrocytes (CECs) can assume many of the hallmark properties of MSCs, such as immunomodulation and immunophenotype. However, unlike MSCs, chondrocytes are known to thrive in suspension, which is important as IA injections release cells into synovial fluid. The goal of this research aims to characterize the growth, immunomodulatory properties, and gene expression of equine CECs as a function of expansion in vitro as well as CEC persistence in the joint after intra-articular injection using a validated model of OA in rats. Additional goals of this research are to 1) determine how CECs may (persistence) or may not (immunomodulation and molecular fingerprint) differ from bone marrow derived MSCs, and 2) compare cellular properties of CECs across age to determine an ideal donor for generating allogeneic therapies. The results shown in chapters 2 and 3 indicate that chondrocytes retain a strong propensity for immunomodulation, that increases with expansion and dedifferentiation does not coincide with other temporal changes in gene expression. Further, these data do not indicate a benefit of neonatal donors. Future in vitro studies should further characterize the immunomodulatory, redifferentiation (chondrogenic) and angiogenic potential of CECs. The preliminary results described in chapter 4 indicate that CECs may have greater persistence than MSCs in the first 3 days post IA injection. Future in vivo studies should focus on determining the symptom- and disease-modifying effects following IA injection of CECs in relevant preclinical models, such as the rodent, horse, and dog.
dc.format.mediumborn digital
dc.format.mediumdoctoral dissertations
dc.identifierLiebig_colostate_0053A_17309.pdf
dc.identifier.urihttps://hdl.handle.net/10217/236000
dc.languageEnglish
dc.language.isoeng
dc.publisherColorado State University. Libraries
dc.relation.ispartof2020-
dc.rightsCopyright and other restrictions may apply. User is responsible for compliance with all applicable laws. For information about copyright law, please see https://libguides.colostate.edu/copyright.
dc.rights.accessEmbargo Expires: 01/09/2025
dc.subjectchondrocytes
dc.subjectosteoarthritis
dc.subjectmesenchymal stromal cells
dc.subjectcellular therapies
dc.titleCulture-expanded articular chondrocytes: a potential cellular therapeutic for osteoarthritis with MSC-like properties
dc.typeText
dc.typeImage
dcterms.embargo.expires2025-01-09
dcterms.embargo.terms2025-01-09
dcterms.rights.dplaThis Item is protected by copyright and/or related rights (https://rightsstatements.org/vocab/InC/1.0/). You are free to use this Item in any way that is permitted by the copyright and related rights legislation that applies to your use. For other uses you need to obtain permission from the rights-holder(s).
thesis.degree.disciplineClinical Sciences
thesis.degree.grantorColorado State University
thesis.degree.levelDoctoral
thesis.degree.nameDoctor of Philosophy (Ph.D.)

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