Cytotherapeutics in Veterinary Medicine

Rick Vulliet, DVM, PhD; University of California, Davis

 

This presentation will describe the various types of stem cells, the fundamentals of isolation and preparation of stem cells and discuss the types of diseases that might benefit from stem cell therapy. This will include some of the recently discovered basic mechanisms- of how stem cells might improve a disease for which veterinary medicine currently lacks an effective cure. In general, any disease that results from a premature loss of cells has the potential for treatment with autologous (from the patient) or allogeneic (donations from closely related donors) adult stem cells. He will compare currently approved clinical trials in human patients with what is doing in canine patients. Specific diseases that will be discussed include degenerative myelopathy, dilated cardiomyopathy, and selected inborn errors of metabolism. Dr. Vulliet will then discuss future applications of stem cells in both human and veterinary medicine.

 

Biographical Profile

 

Dr. Richard Vulliet grew up in southern California and, after Army service, graduated from University of California-Irvine. He attended graduate school and veterinary school in Colorado, receiving his PhD in Pharmacology from the University of Colorado Health Sciences Center and his DVM from Colorado State University. After serving on the faculty of Texas A&M University for five years, he returned to Davis, California where he currently is a Professor of Veterinary Pharmacology and Therapeutics and serves as Director of the Laboratory of Veterinary Cytotherapeutics in the vet school. In the past, he has had several dogs ranging from collies to Australian shepherds. He is currently between dogs, and his three demanding cats share their house with him.

 

About 5 years ago, following a very impressive presentation by br. Darwin Prockop, Director of the Center of Gene Therapy, Tulane University, Dr. Vulliet recognized the therapeutic potential of stem cells in veterinary medicine and has been working with them ever since. He routinely prepares adult bone marrow stem cells from dog, cats and horses and is investigating their application in several veterinary diseases for which veterinary medicine lacks cures.

 

Dr. Vu//iet's research has been supported by the following grant:

 

885; Center of Canine Cytotherapeutics

 

Cytotherapeutics in Veterinary Medicine – conference notes

Is there a Role for Stem Cell Therapy in modern Canine Medicine? Or Is there a Role for Canine Medicine in Stem Cell Therapy?

 

History of therapeutic innovation:

            Natural antibiotics

            Psychotropics

            NSAIDS

            COX inhibitors

            Now what? … cell loss therapeutics, can that be filled with stem cells?

 

Is stem cell therapy ready to attempt to cure real diseases in dogs?  Yes!

 

Sources of stem cells

            Fertilized zygotes

            Embryonic tissues

            Bone marrow – what he picked to work with, they seem to grow well and have good morphology

            Tissue specific cells

            Umbilical cord blood

            Other …

Stem cells are cells that can be developed into different “types” of cells

 

No ethical scientist supports reproductive cloning.

First should ask what can be done, before what should be done.

 

Organ systems that have been investigated in lab for stem cell therapy:

Cardiovascular system – possibly help with heart attacks and/or repair other cells, there was a study that was successful in having cells regrow damaged cells, however it has not been successfully reproduced.  It is still being worked on.  The long term goal is to help with dilated cardiomyopathy in both dogs and humans.  Currently working on a study on Doberman pinschers.  Currently only way to solve DCM in humans, it is to have a heart transplant.  NIH should be working on these studies soon.

           

Nervous system – working on degenerative myelopathy in mainly GSDs.  Growing cells to become neural cells.  This study has been replicated in over ten labs.

           

Respiratory – working on Idopathic pulmonary fibrosis in Westies.  Good laboratory evidence that this can be repaired.  40,000 Americans die from this disease awaiting lung transplants.  Again, NIH could be interested in this.  There has been criteria developed to treat Westies with this condition. 

           

Immune system – LPL deficiency in cats, mini schnauzers and beagles.  Although it is not known if it is a genetic condition in the dog, it is in cats.  Also lethal in humans.  After two injections the lipase went up considerably.

Cat before injection was basically fur and drool, after injections she became a cat who was grooming herself, exhibiting more complex behavior and has become a more normal cat.

            Musculo-skeletal – tendon damage

 

Benefits, even though we are not quite sure how the stem cells are functioning

            Trans-differentiation into desired cell type

            Improved blood flow through increased vascularity

            Immune suppression

            Mitochondrial donation

            Cell fusion

Benefit stem cells can disappear, but the effects can still be beneficial.  They somehow generate native cells that continue repairs.

 

With the discovery of “stem” cells, we think we have found an emerging concept in tissue and injury and repair.  With an injury, there are inflammatory cells and scar cells that are grown at an exaggerated rate, and with “stem” cells this can be altered.

 

Factors affecting clinical outcome – unfortunately, outcomes are unpredictable and unknown.  Dogs that are part of studies ultimately have nothing to loose and much to gain.  Clinical trials in dogs could ultimately be used to spearhead research in humans.

 

www.clinicaltrials.gov  

 

Ultimately, have three centers to develop curative stem cells for dogs - one on the west coast, one in the Midwest and one on the east coast.  This would allow generating “expert” treatment centers and they would allow for great cures and great research to come together.

 

How do you deal with the dog/human bond during curative research?  In theory, you could send the bone marrow cells to them; they grow the cells and return them to your vet who infuses them through a jugular catheter.  However, this is not possible right now during the research stage of the process.

 

Immune problems have not been found – meaning that cells have so far not been rejected by the animal being cured.  Stem cells have been transplanted from humans to mice, rats and pigs with no immune problems.

 

Techniques to grow stem cells so they can be properly formulated for safe injection – there are certain processes that should be followed.