Veterinary Professionals Stem Cell Therapy

Mesenchymal stem cell (MSCs) based therapies in dogs have mainly been focused on bone and cartilage repair in inflammatory diseases such as osteoarthritis. MSCs can differentiate into a tissue specific cell line and/or improve tissue repair through secretion of immunomodulatory and bioactive factors. However, many aspects of the mechanism of action are still not fully understood. Published clinical studies have shown that MSCs offer a promising alternative treatment to current drug therapies [Black et al. Veterinary Therapeutics 8:272-284, 2007; Vilar et al. BMC Veterinary Research 9:131, 2013; Cuervo et al. Int J Mol Sci 15, 13373-13460, 2014].

From our experience with clinical cases we believe that canine MSCs exert an anti-inflammatory action by paracrine signalling. This is a form of cell-cell communication in which a cell produces a signal to induce changes in nearby cells. This is demonstrated in most cases by a remarkable improvement in lameness, within weeks of the injection of the stem cells into the affected joint, which lasts for many months. The long term effects of MSCs in OA are unknown and no information beyond 6 months follow-up is currently available. However, a study in experimental dogs with induced partial thickness cartilage defect showed significant recovery in both clinically and histologically with newly formed cartilage following intra-articular injection of autologous MSCs [Mokbel et al. Clin Exp Rheumatol. 29:275-284, 2011].

What is OrthoStemC™?

VTB’s OrthoStemC™ therapeutic strategy is designed to provide a guided approach to maximising the success of stem cell therapy to manage OA in dogs. The severity of the OA is initially accessed using a validated pre-treatment questionnaire (LOAD) and the improvement in lameness is monitored using the post-treatment questionnaire which is completed by the owner. Validation of LOAD in 222 dogs was described in the study by Walton [Walton MB, Cowderoy E, Lascelle D, Innes JF.  Evaluation of construct and criterion validity for the “Liverpool Osteoarthritis in Dogs” (LOAD) clinical metrology instrument and comparison to two other instruments. PLOS ONE 2013;8(3):e58125]. Novartis has kindly allowed VTB to use LOAD for stem cell therapy.

 

LOAD overview

OrthoStemC™ uses culture expanded autologous adipose-derived stem cells. In comparison with “the same day procedure” where stem cells are isolated from fat tissue (stromal vascular fraction- SVF) and injected into the patient on the same day, the OrthoStemC™ procedure takes around 2 weeks from fat harvest to injection. The SVF contains a heterogeneous pool of cells including adipose-derived stromal cells (ASCs), blood cells, pericytes, fibroblasts and endothelial cells.

Cell culture acts as a selection step to isolate those cells with stem cell-like characteristics. These cells adhere to the plastic of the culture flask and expand in number to form colonies. This cell expansion allows OrthoStemC™ to provide a minimum of 5 million MSCs for injection into each joint.  In SVF the adipose-derived stem cells were shown to represent only 17-18% [Neupane et al. Tissue Eng part A. 2008:4:1007-1015].

The OrthoStemC™ therapeutic scheme includes an assessment of the degree of OA by use of the LOAD questionnaire. LOAD scores the impact of OA on the dog and catagorises the degree of osteoarthritis ranging from mild, through to moderate, severe and extreme. MSCs may be given to reduce lameness in those dogs who have severe and extreme categories and to possibly slow down the progression of osteoarthritis in those dogs who have mild and moderate OA.

Stem cells pathway

OrthoStemC™ cell therapy service is run by veterinary surgeons and scientists. We continue to collect the post-injection clinical data whenever possible. We recognise that after the initial injection the improvement from the lameness lasts a few months and the lameness returns. At this stage, another injection is needed. It is believed that after the second injection the dog stays without lameness for a far longer period. We store the cells frozen for many years so that subsequent injections can be given without having to return to harvest the fat sample again. OrthoStemC™ package includes cells for the first injection and the second injection, including the storage of cells. 

  See our Stem Cell Flyer for Vets