The recent interest in advanced biologic therapies in veterinary medicine has opened up opportunities for new treatment modalities with considerable clinical potential. Studies with mesenchymal stromal cells (MSCs) from animal species have focused on in vitro characterization (mostly following protocols developed for human application), experimental testing in controlled studies and clinical use in veterinary patients. The ability of MSCs to interact with the inflammatory environment through immunomodulatory and paracrine mechanisms makes them a good candidate for treatment of inflammatory musculoskeletal conditions in canine species. Analysis of existing data shows promising results in the treatment of canine hip dysplasia, osteoarthritis and rupture of the cranial cruciate ligament in both sport and companion animals. Despite the absence of clear regulatory frameworks for veterinary advanced therapy medicinal products, there has been an increase in the number of commercial cell-based products that are available for clinical applications, and currently the commercial use of veterinary MSC products has outpaced basic research on characterization of the cell product. In the absence of quality standards for MSCs for use in canine patients, their safety, clinical efficacy and production standards are uncertain, leading to a risk of poor product consistency. To deliver high-quality MSC products for veterinary use in the future, there are critical issues that need to be addressed. By translating standards and strategies applied in human MSC manufacturing to products for veterinary use, in a collaborative effort between stem cell scientists and veterinary researchers and surgeons, we hope to facilitate the development of quality standards. We point out critical issues that need to be addressed, including a much higher level of attention to cell characterization, manufacturing standards and release criteria. We provide a set of recommendations that will contribute to the standardization of cell manufacturing methods and better quality assurance.
Mesenchymal stem cells (MSCs) are multipotent stem cells with wide-ranging clinical applications
due to their ability to regenerate tissue from mesenchymal origin and their capability of suppressing
immune responses, thus reducing the likelihood of graft versus host disease after transplantation.
MSCs can be isolated from a variety of sources including bone marrow, adipose tissue, umbilical
cord blood, and immature teeth. Dental stem cells (DSCs) possess progenitor and immunomodulatory
abilities as the other MSC types and because they can be easily isolated, are considered as attractive
therapeutic agents in regenerative dentistry. Recently, it has been shown that DSCs seeded onto newly
developed synthetic biomaterial scaffolds have retained their potential for proliferation and at the same
time have enhanced capabilities for differentiation and immunosuppression. The scaffolds are becoming
more efficient at MSC priming as researchers learn how short peptide sequences alter the adhesive
and proliferative capabilities of the scaffolds by stimulating or inhibiting classical osteogenic pathways.
New findings on how to modulate the inflammatory microenvironment, which can prime DSCs
for differentiation, combined with the use of next generation scaffolds may significantly improve their
therapeutic potential. In this review, we summarize current findings regarding DSCs as a potential
regenerative therapy, including stem cell priming with inflammatory cytokines, types of scaffolds currently
being explored and the modulation of scaffolds to regulate immune response and promote
growth.
To investigate whether the pig could be considered a suitable model to study lower urinary tract function and dysfunction, the pelvic urethra of 24 slaughtered male pigs were collected, and the associated muscles were macroscopically, histologically and histochemically analyzed. In cross-sections of the urethra, a muscular complex composed of an inner layer of smooth muscle and an outer layer of striated muscle that are not separated by fascial planes was observed. A tunica muscularis, composed of differently oriented smooth muscle bundles, is only evident in the proximal part of the pelvic urethra while, in the remaining part, it contributes to form the prostatic fibromuscular stroma. The striated urethral muscle surrounds the pelvic urethra in a horseshoe-like configuration with a dorsal longitudinal raphe, extending from the bladder neck to the central tendon of perineum. Proximally to the bladder, it is constituted of slow-twitch and fast-twitch myofibers of very small diameter, and embedded in an abundant collagen and elastic fiber net. Moving caudally it is gradually encircled and then completely substituted by larger and compact myofibers, principally presenting circular orientation and fast-twitch histochemical characteristics. So, like in humans, the cranial tract of the muscular system surrounding the pelvic urethra is principally composed of smooth musculature. The striated component cranially may have a role in blocking retrograde ejaculation, while the middle and caudal tracts may facilitate urine and semen flow, and seem especially concerned with the rapid and forceful urethral closure during active continence. Some differences in the morphology and structure between pigs and humans seem due to the different morphology of the 'secondary' sexual organs that develop from the urethral wall and to the different effect of gravity on the mechanics of the urinary system in quadruped and bipedal mammals.
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