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Learn tips about Class IV laser therapy and other health related topics on the Companion Therapy Lasers blog!  Check back weekly for updated posts.

Regen Mythbusters 3

By now we have gained insight into the basics of Regenerative Medicine, such as where PRP and Stem Cells come from and their therapeutic applications for canine patients. It is generally understood that stem cells can be found in any tissue of the body. The two most common sources of stem cells for therapeutic applications are adipose tissue and bone marrow. A common misconception is that adipose derived stem cells provide a superior therapy versus bone marrow aspirate concentrate and that they are easier to collect and process. In this last segment of the Myth Buster Series, we will compare the two sources of stem cells, review their processing differences and determine if there really is a superior choice.

First, let’s consider how Adipose and Bone Marrow Derived Stem Cells are similar:

  • They are both derived from the patient’s own body and are known as autologous adult-derived Mesenchymal stem cells
  • Both can differentiate into cartilage, bone, tendon and ligament cell types.1
  • They can treat certain similar indications with little to no clinical difference.2
  • Both bone marrow and adipose derived stem cells can produce growth factors and anti-inflammatory proteins. These proteins have been shown to contribute to improved healing and reduced inflammation in injured tissues.3
  • Both can be cultured to provide higher cell concentrations.
  • There are commercially available systems to process either sample type.
  • Collection of both Adipose tissue and Bone Marrow require anesthesia.
  • Administration of either Adipose or Bone Marrow derived stem cells is typically done in combination with Platelet Rich Plasma.
  • Fresh samples typically include a heterogenous mixture of several cell types.

Now let’s investigate how Adipose and Bone Marrow Derived Stem Cells are different:

Time frame for processing

  • Fresh Bone Marrow Aspirate Concentrate takes less than 30 minutes from collection to processing and can be done under one anesthetic episode.
  • Fresh Adipose Derived Stem Cells take approximately 3-4 hours to process and require multiple anesthetic or sedative episodes.

Processing requirements

  • Fresh Bone Marrow Aspirate Concentrate involves collecting at least 25 mL of bone marrow from either the femur or humerus. It is then filtered and spun in a processing system for approximately 10 minutes. Once the spin is complete, the plasma is removed and 10% of total volume is collected.
  • Fresh Adipose Derived Stem Cells involve taking approximately 20 grams of adipose under anesthesia, typically harvested from the falciform. The adipose is then mechanically and enzymatically disrupted to separate fat cells, blood cells and the Stromal Vascular Fraction.
    • Stromal Vascular Fraction includes other cell types including white blood cells, fibroblasts, endothelial cells, hematopoietic stem cells and smooth muscle cells.

Concentration of cells

  • In a typical 25 mL collection of bone marrow aspirate, one can expect to have approximately 30,000 stem cells in 3 mL.
  • A typical 20 gram collection of adipose (fresh) will yield 600,000 cells that are considered the Stromal Vascular Fraction.
    • Please Note: There is little evidence in current research that suggests the ideal number of stem cells for treating certain conditions. In one such case, investigated in this peer reviewed paper by B. Carr, et. al., the small number of stem cells found in Bone Marrow Aspirate resulted in similar clinical effects compared to the higher concentration used from Adipose tissue. As our knowledge continues to evolve surrounding indications and specific protocols, these numbers may vary depending on what is being treated.

Open vs. Closed System

  • With Bone Marrow Aspiration, commercially available in-house systems are fully enclosed since the cells are collected via syringe and placed directly into concentrating devices.
  • For Adipose processing, conical tubes are used for adipose digestion and processing, which is classified as an “open system”. This generally means that the samples are exposed to the outside environment which may affect the contents that are being processed. In academic and industry research facilities, it is typically recommended that samples processed utilizing open containers be placed in a fume hood to limit exposure to the surrounding environment.

Equipment Necessary to Process Samples

  • Processing Bone Marrow Concentrate requires a specialized centrifuge designed for concentration of the aspirate. Commercially available kits typically provide syringes, bone marrow collection needles, anticoagulant and concentrating devices.
  • Processing Adipose Tissue requires a specialized centrifuge along with additional equipment including incubator water bath and agitator. Commercially available kits also provide syringes, anticoagulant, enzymes and concentrating devices/ processing tubes.

 

AND THE WINNER IS………………………Well, there really isn’t a winner or a loser in this case. Both Adipose and Bone Marrow Derived Stem Cells can be collected, processed and administered in the same day. Granted, there are differences in the processing times, cell concentrations and collection techniques, however, both therapies provide clinically effective results for similar indications. Deciding which tissue to collect stem cells from is dependent on personal preferences and training. There are numerous educational courses that provide hands-on instruction for either collection technique. If you are interested in learning bone marrow collection and processing, check out one of our upcoming Companion Regenerative University courses. The most important question to ask is “What is my goal for providing this therapy?”. If you answer that question, you may come out with your own Adipose vs. Bone Marrow Derived Stem Cell winner.

Stay tuned for our next blog which will investigate the role of White Blood Cells and their inclusion or exclusion in Platelet Rich Plasma!

 

References:

  1. The comparison of multilineage differentiation of bone marrow and adipose-derived mesenchymal stem cells. Xishan Zhu, Jing Du, Gang Liu. Clin Lab. 2012; 58(9-10): 897–903.
  2. Partial Cranial Cruciate Ligament Tears Treated with Stem Cell and Platelet-Rich Plasma Combination Therapy in 36 Dogs: A Retrospective Study. Canapp S.O. Jr, Leasure C.S., Cox K., Ibrahim V. and Carr B.J. (2016) Front. Vet. Sci. 3:112. doi: 10.3389/fvets.2016.00112
  3. Y.-M. Pers, M. Ruiz, D. Noël, C. Jorgensen, Mesenchymal stem cells for the management of inflammation in osteoarthritis: state of the art and perspectives, Osteoarthritis and Cartilage, Volume 23, Issue 11, November 2015, Pages 2027-2035, ISSN 1063-4584, http://dx.doi.org/10.1016/j.joca.2015.07.004.

 

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To this day, “How frequently should we treat?” remains one of the common questions from operators in the field. This is an important facet of laser therapy, as the operator can induce a quicker response as well as a more sustained response long term when being flexible in treatment session frequency. Laser therapy provides the leeway for the operator to be creative and responsive to a patient’s “glide path” of response to the modality as we initiate laser therapy.

In the past, the “3-2-1″ protocol was a popular treatment approach. In this scenario, the patient would receive three treatments the first week, two the next week, and a single treatment on the third week. Although this is not an ineffective protocol per se, we have since come to see the value in treating patients with a more individualized approach to the frequency of treatment.

Dog Wearing DogglesIf a patient is in pain, we need to address that pain and treat for it. Thus, a daily treatment schedule is recommended here. However, when a patient remains in intractable pain despite standard of care, such as FLUTD cats / pancreatitis / severe degloving injuries / snake bites, a more frequent approach may be indicated. For these patients, it may be advantageous to treat twice or even three times daily. These patients are usually hospitalized, so the opportunity is there for the patient to receive treatment as often as needed in a non-invasive manner. Here, we will provide an overview of some of the common approaches in choosing a treatment frequency. Specific approaches to acute conditions and chronic conditions will be discussed separately.

Once we have attained a significant clinical improvement, it is at that time that we should consider reducing the frequency of treatments. Depending on the specifics of the case and our goals, the patient will undergo either a short course of treatments or continued long term treatment phases. When we have an acute condition such as a laceration or hot spot, our goal is resolution, and a short course is recommended. In this instance, we expect complete resolution. However, when dealing with an incurable condition such as arthritis, our goal is to prevent an active decline while minimizing debilitating symptoms and inducing significant clinical improvement. In this instance, we will begin with an induction phase of frequent treatments until a peak plateau effect is noted. Once we have attained this, we can initiate a less frequent transition phase of treatments. As long as the patient continues to thrive, we can continue to taper this treatment frequency to a long term maintenance phase. These long term maintenance treatments may need to be done as frequently as weekly, or may only be needed every few months. The timeframe of these treatments is individual to the case and the laser operator will need to be flexible, observant, and realistic, as we often see our patients suffering from arthritis having a harder time seasonally (some may be worse in summer vs. winter months).

The client needs to understand our approach with treatment frequency and be open to our setting realistic goals as well. Because therapy laser treatments have a cumulative effect, we can continue to move treatment sessions further apart into a maintenance phase as long as the patient does not have any setbacks. The plan is only the plan – it is crucial for the client to understand that if there is a setback prior to the next scheduled treatment, they need to return as soon as possible to address any decline. Depending on the individual patient, some may be prone to overdoing it due to the fact that we are accelerating their healing while minimizing pain.

It is important to remember that the laser is best applied as an adjunct to standard of care, it is not meant to be a replacement for NSAID, opioid, etc. as per the case specifics, but works best as part of a multimodal approach for pain management. The adept laser operator will be able to design and deliver an optimal treatment frequency as per the patient’s presentation and ensuing glide path of response to laser therapy. Laser therapy as a modality offers the operator the leeway to be flexible in treatment frequency, and this is useful as no two patients are exactly the same in their presentation and physical ability to respond to laser therapy. For example, a young and otherwise healthy patient is expected to have a quicker and more pronounced response than a geriatric patient with a chronic condition and concomitant disease. The young adult field trial dog with a laceration needs to be approached differently than the geriatric Cushingoid patient dealing with arthritis. The addition of laser therapy will enable a quicker return to function while minimizing pain or discomfort during the convalescence period.

As we continue to treat an increasingly wide variety of species and conditions, it is clear that we must be flexible in our approach so as to best address the individual needs of each case.

 

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It is important to remember that laser therapy is a noninvasive modality of medical care. In turn, it is just as important to design a treatment area to be as therapeutic as the treatment itself. Doing so will create an atmosphere closer to a fear-free practice, beneficial not only to the patient, but the client and laser operator as well.

Our primary concern deals with providing medical care on the leading edge of medicine in a safe environment. Whenever a therapy laser is used, any door leading in or out of the treatment area is labelled with a sign indicating that laser therapy is being performed in this area. Within the treatment room, the laser operator and patient will be wearing laser-safe eyewear, as well as anyone else present in the treatment room. Oftentimes, the laser-safe Doggles™ used to protect the patient’s eyes actually have a soothing and calming effect for the patient.

Laser Treatment_Dog Laying Down

The majority of patients receiving laser therapy will have some level of discomfort and mobility impairment, so it is important to remember that these patients would benefit from an easy-to-navigate treatment area. A variety of patients can be effectively treated with a few options for treatment positioning: the floor, a treatment table about waist high, or a raised platform large enough to accommodate the patient and laser operator. Regardless of whichever treatment positioning is chosen, it is crucial that all treatments be done with a comfortable substrate for the patient to be on. A popular option is to use a thick and comfortable fleece. Rolls of these can be purchased and cut to size for any treatment design. They are durable, provide a comfortable environment for the patient, and enhance the therapeutic setting. Also, the fleece is effective in wicking away urine when dealing with incontinent patients. In contrast, performing laser therapy on old, frayed, stained towels detracts from the therapeutic environment.

Some practices also utilize the benefits of white noise in the background, as well as natural lighting by having sky lights installed. The use of aromatherapy has also been documented but its use remains a personal choice for each practice. While it has been shown that some smells like vanilla or mint can have a calming effect, we should remember that the sense of smell is closely associated to the limbic system. Thus, what may be a benign or soothing smell to one person may actually bring up negative memories for someone else.

Laser Treatment_Dog SittingSetting apart an area which is quiet and has little traffic is the perfect setting for laser therapy treatments. The entire experience from check in to check out should be a positive and therapeutic experience for all of those involved. An adept laser operator has a non-threatening body language and adjusts the treatment positioning and delivery as the patient’s body language indicates. A good operator will also be comfortable in discussing the modality and the patient’s progression with the client since the owner is usually present for these treatments. Involving the client for the treatments enhances the fear-free setting for the patient, which in turn enables the operator to deliver an optimal treatment.
The advent of laser therapy promotes a fear-free setting for the patients.

The ability for operators to deliver these treatments is as therapeutic for the operator as it is for the patients entrusted to our care. Designing a therapeutic treatment environment is easily achieved and will greatly enhance the effectiveness.

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