Category Archives: Blog

Stem Cells 101

Welcome to our blog! Since you are here and reading this, you probably are looking for information about stem cells.  Well my friend, you have come to the right place!  You have probably heard of stem cells in the media, whether it be the much discussed controversy regarding embryonic stem cells, hearing about some of your favorite professional athletes getting stem cell therapy as a “miracle cure”, or even an advertisement about stem cell therapy for pets.  It can get a bit confusing, this barrage of information about stem cells, so I am here to give you a brief tutorial about stem cells: what they are, the different types, and who is using them. 

First we need a definition: a stem cell is defined as having the capacity to self renew, and differentiate into different tissue lineages.  This is important for several reasons.  Mainly, it means that stem cells have the capacity to grow in numbers without losing their “stem-ness”. Secondly, it is important because we (us folks in the research world) can manipulate stem cells into becoming specific tissues.  Now, if we back up to the main idea of what a stem cell is, at the purest definition, we really have a limitless potential for differentiation!  Truly, this definition only applies to embryonic stem cells, which I am not going to touch with a ten foot pole.  However, there are many other different kinds of stem cells, if we modify our definition a bit.

If we move one step down the road to differentiation, we still have many populations of stem cells.  These cells still have the capability to self renew, and still can differentiate into different population lineages, although those lineages are more limited.  For instance, the first differentiation in a developing embryo is the formation of the trophoblast, or the cells that will form the placenta.  These cells are still stem cells, and can differentiate into different lineages, but they can only form the cell layers within a specific organ (the placenta).  This again becomes true with cell types that can only form internal organs, bone and musculature, and neural tissue.  This idea is mirrored many times over within an animal, both in stages of early development, and maybe more surprisingly, in an adult animal. 

Adult stem cells are populations of stem cells found within a fully mature body.  Yes, even you have stem cells within your body.  The great thing about adult stem cells is that we, the people of the regenerative medicine world, can use these cells to help re-grow new tissues for you (or your pets) without having to deal with the challenges surrounding embryonic stem cells.  The technology is in place to use self to self treatments.  While there are currently several types of adult stem cells being used to re-grow many different kinds of tissues, I am going to focus on what (in my very biased opinion) is the most important and relevant population of adult stem cells: those used to regenerate muscle, soft tissue, cartilage, and bone.  These are the mesenchymal stem cells (MSCs for short), found in both the bone marrow and fat of adult mammals.   MSCs can be culture expanded while still keeping their stem cell properties, and are being used in clinical applications. For example, culture expanded MSCs are currently used to treat such injuries as: tendon or ligament lesions, mensical tears, osteo-arthritis, and many other orthopedic injuries.

So who, exactly, is using this technology?  At Advanced Regenerative Therapies (ART) we work with veterinarians around the country to treat the above mentioned sports injuries in horses and dogs.  There are several other companies out there that also grow stem cells for veterinary use, and we can get into the differences there another time.  For now I hope you have plenty to think about in regards to stem cells.  Next time we will get more into what happens at ART once a decision has been made to use stem cells to treat an orthopedic injury.  Until then we want to ask you what veterinary applications for stem cells have you heard about or used in your practice?

Disclaimer: Advanced Regenerative Therapies is a commercial veterinary stem cell expansion company.  Information contained within this blog is solely for the general knowledge of the reader.  We do not diagnose any health problems, nor is this information meant to diagnose any health problems or substitute the judgment of a licensed veterinarian.

Bone Marrow Handling at ART – (aka the ARTstem process)

Welcome back readers!  Today I am going to tell you a bit about what happens here at the lab once we receive your bone marrow.  I think we should tell the story from the point of view of a vet, if you happen to be the owner your job is to call your vet and get these updates!  Here we go….

OK! You have found a candidate for stem cell therapy, and have decided to use ART to culture your stem cells.  Now what?  Well first off you need to schedule an appointment to draw a bone marrow aspirate from the patient.  I will skip the details of that step (if you really want to see them click our getting started page and find the appropriate protocol for your needs).  After the aspiration, you want to package the bone marrow and blood-lots and lots of blood, we use the serum to freeze your cells, so don’t short us!—and overnight it to us at the lab.

The next morning at the lab is like Christmas, here is your package all ready for the unwrapping!  We remove the contents and the first order of business is to match your submission form (you included that one right? Here is the link to get a submission form,CanineEquine) to your syringes full of bone marrow and blood.  Once we ensure we have a match, we put the bone marrow into a few centrifuge tubes.  We collect all the nucleated cells from the bone marrow and give them a count.  Then we place the nucleated cells into a cell culture flask, along with some growth medium, and stick them in the incubator.  Now for the fun part- we send along a detailed e-mail form that lists all of the information on your submission form, and how awesome your draw was.

Fast forward about a week.  We have been checking on your cells each day, anxiously awaiting the stem cells to show their happy little selves.  Stem cells like to be close to each other, so they have aggregated together into colonies, where they then divide and multiply until we can see the colony under a microscope.  When the colonies become visible, and we can see several of them in the flask, we “pick them up”.  This process is where we enzymaticaly remove the stem cells from the flask and put them in a small volume so we can get a count.  We place them into a new flask appropriate to the number of cells we counted (so they can be close to each other and happy).  Then we get to talk with you again!  We let you know that your stem cells are healthy and growing.  At this point we can usually determine how much longer until we will have a therapeutic dose ready to ship to you.

Fast forward another week or so.  We have still been checking on your stem cells every day, making sure that if they need attention we give it to them.  At some point in the first 2-3 days after pick up, we moved your cells into the large flasks for final expansion.  Once the cells have completely covered the bottom of these large flasks it is time to cryopreserve them.  We again enzymaticaly remove the cells, put them all into one big tube, and give them a count.  Dependant on your application, we aliquot the cells into 5 million or 10 million cell aliquots.  These go into a special cryopreservation container and into a -80 degree Celsius freezer for several hours.  The stem cells end up in “frozen caveman mode”-just resting and waiting- so when you thaw them they are ready to go to work in the animal! We let you know that the stem cells have been cryopreserved and are ready for shipment.

Now you, the veterinarian, schedule the appointment for injection.  We ship the cells to you, frozen on dry ice, via priority overnight shipment.  Keep this in mind, as we can’t ship for a Monday appointment.  Let us know when your appointment is and if you have a preferred carrier (UPS or FedEx).  We will get the cells shipped out to you, and e-mail you a tracking number for the shipment.

Viola!  You are now an expert on the ARTstem process!  We can’t wait to do our next case with you!

Disclaimer: Advanced Regenerative Therapies is a commercial veterinary stem cell expansion company.  Information contained within this blog is solely for the general knowledge of the reader.  We do not diagnose any health problems, nor is this information meant to diagnose any health problems or substitute the judgment of a licensed veterinarian.

Selecting a Candidate for Stem Cell Therapy

Welcome back to our blog!  Today we are interviewing one of our long time users to get their insight about using stem cells.  Dr. Brent Hague, DVM, Diplomate ACVS, ABVP has graciously agreed to be subject to my questions.  Dr. Hague works at Oakridge Equine Hospital, located in Edmond, Oklahoma.  Oakridge Equine Hospital is a referral practice, and is proud to be home to four board certified equine surgeons.  They house state of the art technology, including a dedicated equine MRI (1.5T), orthopedic and soft tissue surgery suites, and a range of other specialty equipment for diagnosing and treating all of your equine needs.  Go check them out at  Today Dr. Hague and I will be discussing how to select a good candidate for stem cell therapy.  Without further ado…

Me: Tell us a bit about yourself, professionally…any special interests or accreditations?

Dr. Hague (DH):  Our practice is a referral practice, with the main focus in sports medicine and orthopedics, although we do everything.  My interest, in particular, is treatment of the athletic horse.  I like to do arthroscopy and laser surgery; they are probably my two biggest areas of interest.  I completed a surgery residency at Texas A&M, and I became board certified in surgery.  I also became board certified in equine practice.   I have been in an equine practice for 20 years now.  I’ve gained a lot of experience from working with some of the better equine practitioners in the state, and around the country. 

Me: How did you get started using ART?

DH:  The reason I became interested in ART and investing in the technology is due to the positive results we saw.  We were part of the pilot study done at CSU using bone marrow derived stem cells to treat traumatic conditions of the joint that we otherwise felt had a poor prognosis without stem cells.  In that trial with CSU, we did a large number of cases and we definitely saw a positive effect, both in tendon/ligament injuries, and also joint injuries, using stem cells.  As our control we used cases we have treated over the last twenty years, seeing how those horses responded without stem cells post-operatively.  After the study we lost the ability to obtain the cells through CSU. Since the same people who spearheaded that research formed ART, we thought it was a no-brainer to go with someone we trusted to grow our cells. 

Me: What type of injuries do you commonly treat with stem cells?

DH: We, as a practice, or me?  I don’t know how our practice ended up in a bit of a split.  I treat a lot more joint injuries as a total, but our practice as a whole also treats ligament/tendon strains that we think without regenerative therapy would carry a poor prognosis for athletic soundness.  Those are the type of horses we think are good candidates for the stem cells.  For instance, a SDFT that has a core lesion that involves greater than 50% of the cross sectional area of the tendon,  in my mind would be a good candidate for stem cell therapy.  As far as joint treatment, I think the stifle responds well to stem cell therapy; especially if there is a soft tissue component to the injury such as meniscus, collateral ligament, or mild to moderate cartilage damage.  Those horses are good candidates for the stem cells.

Me: To branch off of that a bit: you said you see a split between what you mainly treat and what the other doctors do.  Is there a specific reason why you are more prone to do the joint injuries; is that due to the case load?

DH: I think it is just how the case load has fallen out.  I do a lot of western performance stifle surgeries.  I think just numbers, not that they don’t do them, it just fell out that I have had more cases that fit the selection criteria for stem cell treatment.

Me: Do you find that any one type of injury responds better to stem cells?

DH: The horses that respond better, when talking about a joint, are the ones that have a soft tissue component to the injury causing cartilage damage.  I have not had really good luck in horses that have widespread cartilage loss, where you have exposed bone everywhere in the joint.  Those are end stage joints.  I think it has helped a lot of those horses become comfortable, and become breeding sound-which they weren’t before surgery.  But I haven’t had very good luck in returning those to being an athlete.

Me: Can you tell us a little about the diagnostic work needed to determine when to use stem cell therapy?

DH: Probably the biggest thing, when we are talking about a joint, would be MRI or diagnostic arthroscopy to actually make a visual and tactical assessment of what the cartilage is like and/or soft tissue structure. 

My personal impression…  A lot of these therapies, and especially stem cell therapy, get misused because they get put in everything.  It kind of becomes a buzz to the clients, “I want to use stem cells”, and there are some people who will put them in anything.  I don’t think that is beneficial to anybody.  Say for instance, a horse that we would able to treat with arthroscopy, to take a chip out of a knee, that horse is going to do well anyway, you don’t have to use stem cells too.  You still need to be selective what you use them in, to draw a correlation that definitely it is the stem cells positive effect that is making the horse sound.

Me: we have already touched on this a couple of times, so unless there is anything else you would like to add… Are there certain horses better suited for stem cell therapy?

DH: I think any of them; it is more of an injury dependant kind of thing, and not discipline or breed dependant. A thoroughbred is not going to respond more than a quarter horse.  It depends a lot on the nature of the injury.

Me: Do you take any intermediary steps before deciding on stem cells? (i.e. HA, PRP, IRAP, other)

DH: Let’s take a stifle for instance, say a cutting horse.  We have done the diagnostic work up, the pain blocks to the stifle, we are sure that’s where the pain is.  Radiographically, the stifle is normal, but the horse continues to have inflammation in the stifle. I will try routine injections first.  Say those injections make the horse clinically sound, but they only last maybe 2 months.  I would like those injections to last 4-6 months. If they don’t last that long, and we still don’t see anything on ultrasound and/or changes on the radiographs, we would maybe try a series of IRAP injections first.  For a good many horses, especially reiners and cutters, the IRAP will help whatever is going on in the stifle, they will get sound and we won’t need to do surgery.  If you do the IRAP series and the horse still needs medication to be sound, then it’s time to get on the surgery table and explore the joint.  The sooner you look, the better the prognosis is, because you don’t let the cartilage damage get to the point where there is too much damage to do anything, even with stem cells. 

Me: Do you use other treatment types concurrent with stem cells? (i.e. HA, PRP, IRAP, other)

DH: Usually not.  I usually put the stem cells in the joint with HA, since that is the protocol we have been using for a long time.  But I am using the HA as a carrier and an anti-inflammatory while the stem cells are in there, not as an adjunct treatment.

Me: What kind of success rates do you see?

DH: I think out of that study, to give you some numbers without pulling them out of the air, the original study from CSU with Dr. Frisbie for the joint.  I think that number was 60-some percent that returned to same or better level of use.  That was from a group of horses who otherwise had a poor prognosis.  I think that’s pretty impressive. ***

Me: Me too! Without making you guess any numbers, do you still see those same kinds of results? ****

DH: Yes. I think that overall, stem cell therapy percentages are probably better because those original horses had joints you put a scope in and you say “man, this thing is terrible”.  Then you put stem cells in and we saw a positive result.  Now, we are using stem cells also on some of those horses that are the borderline cases.  Some that may have responded to surgery alone, but we think if we use stem cells it would be an opportunity to augment the healing process.  Including these less severe cases in the overall treated group, improves the overall prognosis.   I don’t think that is a bad thing, we don’t want the patient to get to the point where they have an end stage joint before we intervene.

Me: Is there a particular case that stands out in your mind as being the most remarkable?

DH: One horse in particular that did not return to athletic soundness, but the clients goal was to have the horse breeding sound comes to mind.  A stallion that had a stifle with almost no cartilage left, a mensical tear, and no cartilage on the end of the femur.  It was a grade 4/5 lame, losing weight, couldn’t get on a breeding dummy.  We operated on the horse, cleaned up the joint, and put stem cells in it.  6 months later, he was sound enough they were light riding him—which I didn’t want them to! Still that’s two breeding seasons ago, last breeding season and this breeding season and he is still breeding sound. That’s pretty remarkable.

Me: Anything else you would like to add?

DH: I don’t think so.  I do think you guys do a great job, so thanks!

Me: Thanks Dr. Hague!

*** The published results of the study Dr. Hague is referring to can be found by clicking below (link to ourwebsite)

Frisbie DD, Hague BA, Kisiday JD. Stem cells as a treatment for osteoarthritis. In Proceedings, Am College Vet Surg 2007:39-42.

Ferris DJ, Frisbie DD, Kisiday JD, McIlwraith CW, Hague BA, Major MD, Schneider RK, Zubrod CJ, Kawcak CE, Goodrich LR. Clinical follow-up of horses treated with bone marrow-derived mesenchymal stem cells for musculoskeletal lesions. In Proceedings, Am Assoc Equine Pract 2009; 55:59-60. Submitted Equine Vet J 2010.

**** Watch for new material:

Ferris DJ, Frisbie DD, Kisiday JD, McIlwraith CW, Hague BA, Major MD, Schneider RK, Zubrod CJ, Kawcak CE, Goodrich LR. Clinical follow-up of thirty three horses treated for stifle injury with bone marrow derived mesenchymal stem cells intra-articularly. Vet Surg 2013. In Press.


We would like to thank Dr. Hague for his time, and for agreeing to talk with us.  If you have more questions about selecting a candidate for stem cell therapy, Advanced Regenerative Therapies offers peer-to-peer consultations with our veterinary specialists.  Call us today for more information!


Disclaimer: Advanced Regenerative Therapies is a commercial veterinary stem cell expansion company.  Information contained within this blog is solely for the general knowledge of the reader.  We do not diagnose any health problems, nor is this information meant to diagnose any health problems or substitute the judgment of a licensed veterinarian.

The Ins and Outs of Shipping

Welcome back to the ART blog!  As the weather gets nicer, we get out and ride our horses more.  This unfortunately means they get hurt a bit more, while here at ART things get a little busier.  For me this means extra shipping.  Our entire business here is based around shipping, both incoming packages containing the bone marrow, and outgoing packages with the stem cells.  In some of the ART documentation we reference shipping, but often times there are leftover questions.  Today I am going to address some of the most common questions we get, and some of the issues we see.  Let’s get started!

Incoming Packages

If you are a new client, you have probably read the shipping instructions found on our website.  If you have shipped to us before, you have probably encountered at least one of these situations!  A few of the questions we get from you about incoming packages include:

Why do we need to let you know the package is coming?

Folks, this has nothing to do with permission.  We are here in the building 365 days a year, and we are always accepting your packages.  The reason we ask you to let us know the package is coming is so if it doesn’t show up in the morning we can track it down.  If you don’t want to call us, send us an e-mail.  The best would be if you sent an e-mail that included the tracking number!  Both FedEx and UPS online services offer free e-mail notifications that already include the tracking number, which is a great way to let us know something is headed our way.

Oh no! My package didn’t show up at ART today, what is going to happen to my bone marrow?

This is probably the most frustrating and worrisome situation to find yourself in!  Unfortunately, we all have to place our trust in a 3rd party shipper.  I have asked about getting my pilot license and a private plane to act as a personal courier, but no one else thinks that is a realistic option.  Since we are all stuck with FedEx and UPS, sometimes delays do happen.  Not to worry– if your package arrives within 48 hours (aka the following day) it is usually still viable.  We have very good success with draws arriving 48 hours after they were pulled.

Why do I need to need to put a layer of material between my bone marrow and the ice?

It is crucial that the bone marrow stays at refrigerator temperature, cool but not frozen.  Let me emphasize: not frozen!  If the bone marrow freezes, it causes the cells within the bone marrow to lyse (explode) and there is no way for us to salvage the sample.  When the bone marrow is in direct contact with the ice packs it increases the risk of freezing.  It is also important that the blood does not freeze.  We use the serum to cryopreserve the stem cells, and if there is too much hemolysis in the serum we can’t use that either.  So do make sure there is at least 1 layer of bubble wrap, surgical drape, paper towel, or anything else you can find, between the sample and the ice pack.  Another word about freezing is this: if we sent you a box that arrived the same day as you are drawing a new sample, please DO NOT use the dry ice to ship us back your bone marrow.  It will cause your bone marrow and blood to freeze solid and we will be very sad.

Do you accept shipments on Saturdays?

We sure do!  We don’t accept deliveries to the building on Saturdays, but we have a solution for that.  We ask that you ship the package via FedEx and use the “ship and hold” option (also, please make sure you check the Saturday delivery option or the package won’t come until Monday).  The shipping address for Saturday deliveries is: 3800 Weiker Dr, Fort Collins, CO 80524. You must send us the tracking number for the package and let us know it is coming as we don’t go check for boxes out there every Saturday.  Call us anytime and we can walk you through all the steps either online or on your FedEx Airbill.

Outgoing Packages

To start off with there are a few basic things you need to know about how we ship your stem cells.  The stem cells have been cryopreserved and are stored at very cold temperatures.  They need to stay frozen until the moment you are ready to inject them.  Therefore, we ship all of our stem cells on dry ice and we utilize overnight delivery.  We generally ship via UPS, but please let us know if FedEx is much more reliable for you.  Appointments should be made Tuesdays through Fridays.  We cannot ship for Monday appointments.

How much notice do I need to give to get my stem cells shipped?

We appreciate as much notice as possible; please let us know at least the day before you want the cells shipped.  That being said, we do our best to accommodate same day shipping, so long as the requests are made before 1pm MST.  We cannot guarantee same day shipping on ship requests made after 1pm MST.

What happens if my package arrives late?  Will my cells be OK?

If your package doesn’t arrive by the guaranteed shipping time (usually 10:30am), please give us a call.  There are instances where the package is just running a bit late, and we can usually call UPS or FedEx and get the driver to hurry up a bit.  In other instances, such as a weather delay, the package may need to come the next day.  We make sure to pack enough dry ice in every box to ensure your cells will still be frozen after 48 hours.  If a next day appointment isn’t going to work for your client, we can arrange to have the cells shipped back to ART and reschedule for a future date.

Our clinic is located in a rural area without morning delivery, what options do we have?

We can always arrange for your stem cells to be shipped to arrive the day before the appointment.  This option allows you to have an early appointment, even when you don’t have early delivery service.  We can also ship the cells to you ahead of time if you have a liquid nitrogen storage tank in which the stem cells can be stored indefinitely.

The only time I can inject my patient is on a Monday.  What can I do?

We do not recommend Monday appointments.  If you have a liquid nitrogen tank we can ship the stem cells to you the week before the appointment, and you can store them in the tank until your appointment.  If you are willing to take a risk, we can ship the stem cells to arrive the Friday or Saturday before the appointment.  Someone will need to come in during the weekend and check that there is still dry ice in the box.  The dry ice will need to be replenished if it is running low (you can usually purchase dry ice at a local grocery store).  Please note that in the case of a shipping delay the package won’t arrive until Monday, and the cells will most likely be thawed and not suitable for use.

Do you have more questions about shipping?  Call today and I will answer any of your questions! (970)212-0749

Disclaimer: Advanced Regenerative Therapies is a commercial veterinary stem cell expansion company.  Information contained within this blog is solely for the general knowledge of the reader.  We do not diagnose any health problems, nor is this information meant to diagnose any health problems or substitute the judgment of a licensed veterinarian.