Point-of-care production and immediate delivery

Autologous Bone Marrow Aspirate Concentrate (BMAC) and Stromal Vascular Fraction (SVF) are methods of harvesting mesenchymal stem cells and growth factors from the patient’s own bone marrow or adipose tissue for immediate use, normally taking less than 30 minutes to prepare. The most common clinical application of stem cells in clinical veterinary medicine is the treatment of musculoskeletal problems in horses and dogs (Fortier & Travis 2011, Diekman and Guilak 2013) Both BMAC and SVF derived cells have a broad multipotency with differentiation into a number of cell lineages, including adipocytic, osteocytic and chondrocytic lineages (Parker and Katz, 2006).

The easy and repeatable access to subcutaneous adipose tissue in the dog makes harvesting adipose derived mesenchymal cells (AD-MSCs/SVF) a real option in the treatment of canine osteoarthritis. Approximately 500-fold greater numbers of fresh MSCs derived from equivalent amounts of adipose versus bone marrow provide a clear advantage for using AD-MSCs (Schaffler and Buchler 2007; Fraser et al 2006). MSCs are known to secrete cytokines and growth factors, and may stimulate recovery in a paracrine manner (Gimble et al 2007; Caplan and Dennis, 2006). BM-MSCs secrete interleukin-1 receptor antagonist (IL-1Ra) which was determined to be the specific mechanism reducing inflammation and fibrosis (Oritz et al 2007).

It is further postulated that MSCs may engraft in synovium or in cartilaginous lesions and either influence the local cells to differentiate into cartilage or AD-MSCs themselves may differentiate into cartilage (Nathan et al 2003; Black et al, 2007). A placebo-controlled, double-blind study in dogs with hip OA demonstrated intra-articular AD-MSc therapy resulted in improved subjective orthopaedic examination scores, with lameness, range of motion and pain on manipulation improved relative to control animals (Black et al 2007). Vilar et al (2014) demonstrated a single intra-articular administration of AD-MSC therapy decreased pain and lameness in dogs with hip OA based on objective force plate analysis.

In the horse, it has been shown that MSCs placed in an environment of injury express cytokines and growth factors that promote repair or activate compensatory mechanism and endogenous stem cells within the tissue, especially with regards to tendon or ligament injury (Chopp et al 2000; Crovace 20102). Administered intra-articularly, AD-MSC’s or BM-MSCs in an equine model of osteoarthritis (Frisbie et al 2009) has been shown to decrees levels of prostaglandin E2.

Advantages of patient-side harvesting and administration of AD-MSCs or BM-MSCs:
• Safer and more affordable than sending material to a laboratory for processing
• Clinically more effective on a cell-for-cell basis
• Higher cell viability
• Have greater cell numbers and can be delivered in greater numbers (BMAC Total monoucleated cells – 18 x106/ml, adipose can yield 500-fold greater)
• A single procedure for the patient, saving time, cost, anesthetic risk and speed to recovery.

Nupsala Veterinary Services supplies two of the leading systems on the market capable of processing either bone marrow or adipose tissue from dogs or horses. These are point-of-care, multifunctional systems for concentrating autologous cells and tissues (PRP, BMAC and Adipose Concentrate) each acting as a single device platform for the preparation of multiple biomaterials with a rapid 14 minute processing time. Both systems are available to purchase or via our affordable mobile lab service.

Further Reading

1) Effect of adipose-derived mesenchymal stem and regenerative cells on lameness in dogs with chronic osteoarthritis of the coxofemoral joints: a randomized, double-blinded, multicenter, controlled trial.
Black LL, Gaynor J, Gahring D, Adams C, Aron D, Harman S, Gingerich DA, Harman R.
Vet Ther. 2007 Winter;8(4):272-84.

2) Implantation of bone marrow-derived mesenchymal stem cells demonstrates improved outcome in horses with overstrain injury of the superficial digital flexor tendon.
Crovace A, Lacitignola L, Rossi G, Francioso E.
Vet Med Int. 2010;2010:250978. doi: 10.4061/2010/250978. Epub 2010 Mar 22.

3) Concentration of bone marrow total nucleated cells by a point-of-care device provides a high yield and preserves their functional activity.
Hermann PC, Huber SL, Herrler T, von Hesler C, Andrassy J, Kevy SV, Jacobson MS, Heeschen C.
Cell Transplant. 2008;16(10):1059-69.