Why the hype - What are microRNAs and why do they provide unique investigative, diagnostic, and therapeutic opportunities in veterinary medicine?

MicroRNAs (miRNAs) are small, non-coding RNAs that regulate gene expression by inhibiting translation or inducing transcript degradation. MiRNAs act as fine-tuning factors that affect the expression of up to 60% of all mammalian protein coding genes. In contrast to proteins, there is widespread conservation of miRNA sequences across species. This conservation strongly suggests that miRNAs appeared early in evolution and have retained their functional importance. Cross-species conservation provides advantages when compiling candidate markers for health and disease compared to protein-based discoveries. This broad utility is accompanied by the emergence of inexpensive sequencing protocols for the identification of all RNAs in a sample (including miRNAs). With the use of miRNA mimics and antagonists, unique research questions can be answered in biological systems with 'cause and effect' methodology. MiRNAs are readily detectable in blood making them attractive candidates as biomarkers for disease. Here, we review their utility as biomarkers and their potential as therapeutic agents or targets to combat disease.

Pourquoi la frénésie ­ Que sont les microRNAs et pourquoi fournissent-ils des opportunités uniques pour investiguer, diagnostiquer et traiter en médecine vétérinaire? Les microRNAs (MiRNAs) sont de petits segments non-codants d'ARN qui régulent l'expression des gènes en inhibant la traduction ou en induisant la dégradation du transcript. Les MiRNAs agissent comme des facteurs d'ajustement fin qui affectent l'expression pouvant aller jusqu'à 60 % de tous les gènes mammaliens codant pour des protéines. Contrairement aux protéines, il y a un conservatisme étendu des séquences des miRNA à travers les espèces. Ce conservatisme suggère fortement que les miRNAs sont apparus tôt dans l'évolution et ont conservé leur importance fonctionnelle. La conservation inter-espèces fournie des avantages lors de la compilation de candidats marqueurs pour la santé et la maladie comparativement aux découvertes basées sur les protéines. Cette large utilité est accompagnée par l'émergence de protocoles de séquençage peu dispendieux pour l'identification de tous les ARNs dans un échantillon (incluant miRNAs). Avec l'utilisation d'imitations et d'antagonistes de miRNA, des questionnements rares en recherche peuvent être répondus dans des systèmes biologiques avec des méthodologies « cause et effet ¼. Les miRNAs sont facilement détectables dans le sang ce qui les rend des candidats attirants comme biomarqueurs de maladies. Ici, nous faisons une revue de leur utilité comme biomarqueurs et leur potentiel comme agents thérapeutiques ou cibles pour combattre des maladies.(Traduit par Dr Serge Messier).

Improved expansion of equine cord blood derived mesenchymal stromal cells by using microcarriers in stirred suspension bioreactors.

Equine mesenchymal stromal cells (MSCs) are increasingly investigated for their clinical therapeutic utility. Such cell-based treatments can require cell numbers in the millions or billions, with conventional expansion methods using static T-flasks typically inefficient in achieving these cell numbers. Equine cord blood-derived MSCs (eCB-MSCs), are promising cell candidates owing to their capacity for chondrogenic differentiation and immunomodulation. Expansion of eCB-MSCs in stirred suspension bioreactors with microcarriers as an attachment surface has the potential to generate clinically relevant numbers of cells while decreasing cost, time and labour requirements and increasing reproducibility and yield when compared to static expansion. As eCB-MSCs have not yet been expanded in stirred suspension bioreactors, a robust protocol was required to expand these cells using this method. This study outlines the development of an expansion bioprocess, detailing the inoculation phase, expansion phase, and harvesting phase, followed by phenotypic and trilineage differentiation characterization of two eCB-MSC donors. The process achieved maximum cell densities up to 75,000 cells/cm2 corresponding to 40 million cells in a 100 mL bioreactor, with a harvesting efficiency of up to 80%, corresponding to a yield of 32 million cells from a 100 mL bioreactor. When compared to cells grown in static T-flasks, bioreactor-expanded eCB-MSC cultures did not change in surface marker expression or trilineage differentiation capacity. This indicates that the bioreactor expansion process yields large quantities of eCB-MSCs with similar characteristics to conventionally grown eCB-MSCs.