Topics of Discussion

CURRENT STEM CELL RESEARCH

Andy Hoffman, D.V.M., D.V.Sc., D.A.C.V.I.M., Professor, Director, Lung Stem Cell Laboratory and Jose Garcia-Lopez, DVM, DACVS, Associate Professor.

Understanding Stem Cell Potency: Can the Veterinary Profession Do Better?

Stem cells have now captivated the veterinary profession and for good reason.  These cells produce a vast array of molecules that promote repair and regeneration of damaged tissue. The signals produced by stem cells are so numerous and complex that they cannot yet be reproduced in the laboratory.  Harnessing their potential is the central focus for many laboratories around the world. The hope is that stem cells will revitalize tissue in healing wounds, and reduce inflammation, fibrosis, and auto-immunity. It’s a tall order but there is good evidence from animal models that stem cells or their derivatives can accomplish these goals. 

It’s important to keep in mind that veterinary stem cell research is in the beginning phases, every new group of data is exciting and at times there are unforeseen circumstances that may change the anticipated outcome of the research.

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Image III: Equine mesenchymal stem cells in culture.

While the science of animal stem cells is in its early stages, stem cell purveyors have emerged. Thus, a veterinarian may procure a kit to harvest bone marrow or fat, and a company will isolate mesenchymal stem cells (MSCs) and send them back overnight, for delivery to the patient. To do so, the stem cell companies have to overcome several logistical barriers in order to deliver efficiently and reliably, a product which is also safe. Recent data supports the clinical benefits of commercially derived MSCs in clinical trials (e.g. superficial digital flexor injury). Although company websites quote that a majority of horses respond to their stem cell therapies, durable benefits directly attributable to stem cells have been very difficult to demonstrate, and trial design has been limited. Nevertheless, there is increasing evidence that MSCs improve healing, in ways that we do not completely understand.

In contrast to the tight regulation of human stem cell commerce, regulatory agencies (FDA, USDA) have not yet prioritized regulation of the development of animal stem cells, nor have they promulgated regulations that address interstate commerce of animal stem cells.  For emerging therapeutics, commercialization ordinarily speeds up progress.  Owing to the lack of regulation at present, incentives are lacking for commercial entities to evaluate potency, or the use of allogeneic (mismatched) versus autologous (patient specific, matched) cells. University and local laboratories are likely to play key roles in the design and development of more effective stem cell therapies, since veterinary development of these products follows that of human products in this class. For example, the National Institute of Health through PACT (Production Assistance to Cell Therapies, www.pactgroup.net) is becoming a preferred venue for human clinical trials.

Finally, as a veterinary profession, we need to better understand the mechanisms of action of stem cells, and thus how to define their potency.  Recent research shows that “whole cells may be inessential” to many of the therapeutic effects of stem cells, i.e., lysed cells or concentrates of conditioned media used to growth the cells perform just as well.  Stem cells release chemicals and exosomes’ (secreted biologically active packets of membrane bound proteins and nucleotides) into the surrounding media or tissues that contain much of the healing properties. Thus we need to consider potency of the cells and their secreted products equally.

In summary, when new and improved stem cell therapies with well-defined efficacy and potency endpoints are developed, the veterinary profession will enjoy an incredibly powerful tool to improve the health of animals.