Chondrogenic differentiation potential of adult and fetal equine cell types

Adam, Emma; Janes, Jennifer; Lowney, Rachael; Lambert, Joshua; Thampi, Parvathy; Stromberg, Arnold J.; MacLeod, James N.

doi:10.1111/vsu.13183

Cited by 8 publications

(22 citation statements)

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“…Cellular proliferation has been shown to be positively correlated with regenerative potential (4). Bone marrow (BM)-and adipose tissue (AT)-derived MSCs are currently the choice of therapy, where BM-MSCs have shown higher potential to treat cartilage and bone injuries (5,6). For successful therapies, a substantial number of cells are needed, which often requires extensive ex vivo cell expansion prior to implantation.…”

Section: Introductionmentioning

confidence: 99%

Cellular Proliferation of Equine Bone Marrow- and Adipose Tissue-Derived Mesenchymal Stem Cells Decline With Increasing Donor Age

2020

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Background: Bone marrow (BM)- and adipose tissue (AT)-derived mesenchymal stem cells (MSCs) are used increasingly for autologous cell therapy in equine practice to treat musculoskeletal and other injuries. Current recommendations often call for 10–100 million MSCs per treatment, necessitating the expansion of primary cells in culture prior to therapeutic use. Of concern, human and rodent studies have shown a decline of both MSC recovery from sampled tissue and in vitro proliferative capacity with increasing donor age. This may be problematic for applications of autologous cell-based therapies in the important equine demographic of older patients.Objectives: To investigate the effect of donor age on the cellular proliferation of equine BM- and AT-MSCs.Study Design:In vitro study.Methods: BM- and AT-MSCs and dermal fibroblasts (biological control) were harvested from horses in five different age groups (n = 4, N = 60); newborn (0 days), yearling (15–17 months), adult (5–8 years), middle-aged (12–18 years), and geriatric (≥22 years). Proliferation of the cells was tested using an EdU incorporation assay and steady state mRNA levels measured for targeted proliferation, aging, and senescence biomarkers.Results: The cellular proliferation of equine BM- and AT-MSCs declined significantly in the geriatric cohort relative to the younger age groups. Proliferation levels in the two MSC types were equally affected by donor age. Analysis of steady state mRNA levels showed an up-regulation in tumor suppressors, apoptotic genes, and multiple growth factors in MSCs from old horses, and a down-regulation of some pro-cycling genes with a few differences between cell types.Main Limitations: Potential age-dependent differences in cell function parameters relevant to cell-therapy application were not investigated.Conclusions: The cellular proliferation of equine BM- and AT-MSCs declined at advanced donor ages. High levels of in vitro proliferation were observed in both MSC types from horses in the age groups below 18 years of age.

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Section: Introductionmentioning

confidence: 99%

Cellular Proliferation of Equine Bone Marrow- and Adipose Tissue-Derived Mesenchymal Stem Cells Decline With Increasing Donor Age

2020

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“…In comparing GOcats' inclusion of re-evaluated has_part relations to the traditional method of ignoring has_part relations altogether and to the erroneous method of misinterpreting native has_part directionality, we illuminate the theoretical extent of information loss or potential for misinterpretation of has_part relations, respectively. Furthermore, in two independent enrichment analyses of real data-from a publicly available breast cancer dataset [13] and from preliminary data investigating horse cartilage development [14], we demonstrate that GOcats'…”

Section: Go Categorization Suite (Gocats)mentioning

confidence: 91%

Advances in Gene Ontology Utilization Improve Statistical Power of Annotation Enrichment

Hinderer

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MacLeod

et al. 2018

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Gene-annotation enrichment is a common method for utilizing ontology-based annotations in these gene and gene-product centric knowledgebases. Effective utilization of these annotations requires inferring semantic linkages by tracing paths through the ontology through edges in the ontological graph, referred to as relations.However, some relations are semantically problematic with respect to scope, necessitating their omission lest erroneous term mappings occur. To address these issues, we present GOcats, a novel tool that organizes the Gene Ontology (GO) into subgraphs representing user-defined concepts, while ensuring that all appropriate relations are congruent with respect to scoping semantics. Here, we demonstrate the improvements in annotation enrichment by re-interpreting edges that would otherwise be omitted by traditional ancestor path-tracing methods.We demonstrate that GOcats' unique handling of relations improves enrichment over conventional methods in the analysis of two different gene-expression datasets: a breast cancer microarray dataset and several horse cartilage development RNAseq datasets. With the breast cancer microarray dataset, we observed significant improvement (one-sided binomial test p-value=1.86E-25) in 182 of 217 significantly enriched GO terms identified from the conventional path traversal method when GOcats' path traversal was used. We also found new significantly enriched terms using GOcats, whose biological relevancy has been experimentally demonstrated elsewhere. Likewise, on the horse RNAseq datasets, we observed a significant improvement in GO term enrichment when using GOcat's path traversal: one-sided binomial test p-values range from 1.32E-03 to 2.58E-44.* IA_PO refers to a graph created with only is_a and part_of relationship edges.

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“…Tissue samples were collected across six experimental groups (Table 7) and compared for differential gene expression at a transcriptome level using mRNA sequencing. Sample collection methods have been described previously [10,25] and were conducted in accordance with an approved University of Kentucky Institutional Animal Care and Use Committee protocol (# 2014–1215). Total RNA was isolated using a commercial kit (Qiagen RNeasy Micro Kit, cat# 74004) after homogenization on ice as previously described [26].…”

Section: Methodsmentioning

confidence: 99%

“…In comparing GOcats’ inclusion of re-evaluated has_part relations to the traditional method of ignoring has_part relations altogether and to the erroneous method of misinterpreting native has_part directionality, we illuminate the theoretical extent of information loss or potential for misinterpretation of has_part relations, respectively. Furthermore, in two independent enrichment analyses of real data—from a publicly available breast cancer dataset [9] and from samples investigating horse cartilage development [10], we demonstrate that GOcats’ reinterpretation of has_part can retain all information from GO while drawing appropriate categorical inferences in the context of annotation enrichment. Finally, we show that this reinterpretation has the added benefit of improving the statistical power of annotation enrichment analyses.…”

Section: Introductionmentioning

confidence: 98%

Advances in gene ontology utilization improve statistical power of annotation enrichment

et al. 2019

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Gene-annotation enrichment is a common method for utilizing ontology-based annotations in gene and gene-product centric knowledgebases. Effective utilization of these annotations requires inferring semantic linkages by tracing paths through edges in the ontological graph, referred to as relations. However, some relations are semantically problematic with respect to scope, necessitating their omission or modification lest erroneous term mappings occur. To address these issues, we created the Gene Ontology Categorization Suite, or GOcats—a novel tool that organizes the Gene Ontology into subgraphs representing user-defined concepts, while ensuring that all appropriate relations are congruent with respect to scoping semantics. Here, we demonstrate the improvements in annotation enrichment by re-interpreting edges that would otherwise be omitted by traditional ancestor path-tracing methods. Specifically, we show that GOcats’ unique handling of relations improves enrichment over conventional methods in the analysis of two different gene-expression datasets: a breast cancer microarray dataset and several horse cartilage development RNAseq datasets. With the breast cancer microarray dataset, we observed significant improvement (one-sided binomial test p-value = 1.86E-25) in 182 of 217 significantly enriched GO terms identified from the conventional path traversal method when GOcats’ path traversal was used. We also found new significantly enriched terms using GOcats, whose biological relevancy has been experimentally demonstrated elsewhere. Likewise, on the horse RNAseq datasets, we observed a significant improvement in GO term enrichment when using GOcat’s path traversal: one-sided binomial test p-values range from 1.32E-03 to 2.58E-44.

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Chondrogenic differentiation potential of adult and fetal equine cell types

Cited by 8 publications

References 54 publications

Cellular Proliferation of Equine Bone Marrow- and Adipose Tissue-Derived Mesenchymal Stem Cells Decline With Increasing Donor Age

Cellular Proliferation of Equine Bone Marrow- and Adipose Tissue-Derived Mesenchymal Stem Cells Decline With Increasing Donor Age

Advances in Gene Ontology Utilization Improve Statistical Power of Annotation Enrichment

Advances in gene ontology utilization improve statistical power of annotation enrichment

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