Department of Large Animal Clinical Sciences

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https://hdl.handle.net/10919/24261

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Browsing Department of Large Animal Clinical Sciences by Author "Barrett, Jennifer G."

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    Multi-differentiation potential is necessary for optimal tenogenesis of tendon stem cells
    Rajpar, Ibtesam; Barrett, Jennifer G. (2020-04-09)
    Background Tendon injury is a significant clinical problem due to poor healing and a high reinjury rate; successful treatment is limited by our poor understanding of endogenous tendon stem cells. Recent evidence suggests that adult stem cells are phenotypically diverse, even when comparing stem cells isolated from the same tissue from the same individual, and may in fact exist on a spectrum of proliferation and differentiation capacities. Additionally, the relationships between and clinical relevance of this phenotypic variation are poorly understood. In particular, tenogenic capacity has not been studied in comparison to tenogenic differentiation and cell proliferation. Toward this end, we performed a comprehensive assessment of cell proliferation and differentiation capacity toward four connective tissue lineages (tendon, cartilage, bone, and adipose) using tendon stem cell lines derived from single cells released directly from tendon tissue to (1) evaluate the differences, if any, in tenogenic potential, and (2) identify the relationships between differentiation phenotypes and proliferation capacity. Methods Tendon stem cells were derived from the endotenon of superficial digital flexor tendon from 3 horses. The cell suspension from each horse was separately plated simultaneously (1) at moderate density to generate a heterogenous population of cells—parent tendon cell line—and (2) at low density to separate single cells from each other to allow isolation of colonies that derive from single mother cells—clonal tendon stem cell lines. Thirty clonal tendon stem cell lines—10 from each horse—and each parent tendon cell line were assessed for tenogenesis, tri-lineage differentiation, and cell proliferation. Differentiation was confirmed by lineage-specific cell staining and quantified by the relative gene expression of lineage-specific markers. Statistical significance was determined using analysis of variance and post hoc Tukey’s tests. Results Three distinct differentiation phenotypes—differentiation potency toward all 4 tissue lineages and two tri-lineage differentiation potencies—were identified in tendon clonal stem cell lines. These phenotypes were differentiation toward (1) tendon, cartilage, bone, and adipose (TCOA); (2) tendon, cartilage, and bone (TCO); and (3) tendon, cartilage, and adipose (TCA). Further, clonal cell lines that differentiated toward all four lineages had the highest expression of scleraxis and mohawk upon tenogenesis. Moreover, cell proliferation was significantly different between phenotypic groups, as evidenced by increased numbers of cumulative cell population doublings in clonal cell lines that did not differentiate toward adipose. Conclusions Our study provides evidence of the heterogenous character of adult stem cells and identifies key differences in tendon stem cell differentiation and proliferative potentials from the same individual and from the same tendon. Isolation of tendon stem cell lines with the capacity to differentiate into all four connective tissue lineages may yield improved therapeutic benefits in clinical models of repair and promote a native, regenerative phenotype in engineered tendons. Future studies may be targeted to understanding the functional contributions of each tendon stem cell phenotype in vivo and identifying additional cell phenotypes.
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    A Set of Grand Challenges for Veterinary Regenerative Medicine
    Barrett, Jennifer G. (Frontiers in Veterinary Science, 2016-03-04)
    “Regenerative medicine” refers to therapies that aim to restore normal form and function using the body’s own biological machinery, such as stem cells and biologics. The use of regenerative medicine to treat injury and disease offers new hope to cure previously frustrating diseases and conditions. However, commercialization of biologic therapies in veterinary medicine has outpaced the speed of clinical research, and we are at risk of harming the reputation and standing of regenerative medicine before it has been fully optimized and developed. In response to this, international regulation of Veterinary Regenerative Medicine is underway... The open access format for Veterinary Regenerative Medicine offers a venue for dissemination of information about veterinary therapeutics that can accelerate translational medicine and the concept of “One Health.”