Canine atopic dermatitis (AD) is a common skin disease with a 10–15 per cent prevalence. Current treatments vary in their efficacy and safety. The immunomodulatory properties of mesenchymal stem cells (MSCs) make them a promising alternative treatment. The aim of this study was to evaluate the therapeutic efficacy and safety of allogeneic canine adipose MSCs (cAd‐MSCs) in dogs with refractory AD. Twenty‐six dogs, suffering from AD for at least 12 months, not responding to conventional therapy, received an intravenous dose of 1.5×10 6 cAd‐MSCs/kg bodyweight. Clinical signs, haematological and biochemistry profiles, and AD severity were assessed in a six‐month follow‐up using a validated scoring system (Canine Atopic Dermatitis Extent and Severity Index, version 4 (CADESI‐04)). The degree of pruritus was quantified using a validated visual analogue scale, and also owner's global assessment of treatment efficacy. Twenty‐two animals completed the study. Pruritus and CADESI‐04 scores decreased significantly after one week or month of treatment, respectively, and remained stable for six months. Owner's global assessment score was 2.15±1.15 for all the animals in the study. In conclusion, systemic administration of allogeneic cAd‐MSCs appeared to be a simple therapy with positive outcome in the remission of clinical signs for AD refractory to conventional medications, for at least six months and with no adverse events.
Background: Mesenchymal stem cells may offer therapeutic potential for asthma due to their immunomodulatory properties and host tolerability, yet prior evidence suggests that bloodborne progenitor cells may participate in airway remodeling. Here, we tested whether mesenchymal stem cells administered as anti‐inflammatory therapy may favor airway remodeling and therefore be detrimental.Methods: Adipose tissue‐derived mesenchymal stem cells were retrovirally transduced to express green fluorescent protein and intravenously injected into mice with established experimental asthma induced by repeat intranasal house dust mite extract. Controls were house dust mite‐instilled animals receiving intravenous vehicle or phosphate‐buffered saline‐instilled animals receiving mesenchymal stem cells. Data on lung function, airway inflammation, and remodeling were collected at 72 h after injection or after 2 weeks of additional intranasal challenge.Results: The mesenchymal stem cells homed to the lungs and rapidly downregulated airway inflammation in association with raised T‐helper‐1 lung cytokines, but such effect declined under sustained allergen challenge despite a persistent presence of mesenchymal stem cells. Conversely, airway hyperresponsiveness and contractile tissue underwent a late reduction regardless of continuous pathogenic stimuli and inflammatory rebound. Tracking of green fluorescent protein did not show mesenchymal stem cell integration or differentiation in airway wall tissues.Conclusions: Therapeutic mesenchymal stem cell infusion in murine experimental asthma is free of unwanted pro‐remodeling effects and ameliorates airway hyper‐responsiveness and contractile tissue remodeling. These outcomes support furthering the development of mesenchymal stem cell‐based asthma therapies, although caution and solid preclinical data building are warranted.
Osteoarthritis (OA) commonly causes lameness in the horse and has a great impact in performance animals. Due to the limitations of current medical therapies, allogenic mesenchymal stem cells (MSCs) may become an alternative method to control inflammation, reduce tissue damage and pain, and therefore improve lameness. We present the results of a regulatory clinical trial testing adipose derived MSCs (Horse Allo 20) in veterinary (Agencia Española del Medicamento y Productos Sanitarios, AEMPS, Spanish Medicines Agency, Reference number 325/ECV) involving a total number of 80 participants and with 90 days of follow-up period. The manufacturing process of Horse Allo 20 was robust with no influence of the adipose tissue donor (gender, age or breed), sample origin (intraperitoneal or subcutaneous) or storage conditions (fresh versus frozen product presentations) on the quality, safety and efficacy of the drug product. An in vivo safety study showed that local and systemic tolerance was safe even after repeated intra-articular (IA) administration (three injections). An in vivo efficacy study demonstrated the efficacy of the treatment after one or two injections by a reduction in lameness (P<0.05) for an extended period of time (90 days), decreasing the need for prolonged local and/or systemic anti-inflammatory therapies and their well-known deleterious effects and toxicities.
1 February 2020 in Environmental Health Perspectives
Environmental Health Perspectives is an Open Access journal published by the National Institute of Environmental Health Sciences. Environmental Health Perspectives is an Open Access journal published by the National Institute of Environmental Health Sciences.