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Have you heard of the term “prolotherapy” and wondered: “Is that the same as platelet rich plasma or stem cell therapy?”. If you answered “yes”, you’re not alone! Prolotherapy, also known as “proliferation therapy” or “regenerative injection therapy”, is a term that is used to describe an area of therapeutics that result in proliferation and healing of damaged tissues.

Sounds very familiar to regenerative medicine, doesn’t it? That’s because prolotherapy works under the same principal of utilizing the body’s own healing capabilities to heal and repair tissues. But what makes it different than platelet rich plasma and stem cell therapies? In this blog, we will explore the uses of prolotherapy, what it consists of and how it differs in its method of action from the regenerative therapies we have come to understand.

 

What is prolotherapy?

Prolotherapy is a therapy in which an irritant solution is injected at a site of injury/pain with the goal of eliciting a temporary, low grade inflammatory response resulting in healing and repair of connective tissues. The irritant typically used for these procedures consists of 12-25% of Dextrose, the naturally occurring form of glucose.

 

How does prolotherapy work?

It is generally accepted that when a solution consisting of more than 10% dextrose is injected into a tissue, it creates an osmotic gradient outside of the cells. When a prolotherapy solution is injected into the tissue, it draws out water from within the cells, resulting in their lysis, also described as osmotic shock. When cells undergo apoptosis, they release signals to the body to undergo a wound-healing cascades at the specific sites of injuries. In essence, prolotherapy creates a minor injury to the tissue with the goal of an increased healing response to the tissue.1

 

What is prolotherapy typically used for?

Prolotherapy has been reported to be useful in facilitating the repair of weakened or unstable tendons and ligaments as well as various forms of spinal pathologies resulting in pain. While numerous studies have attempted to investigate prolotherapy for use in osteoarthritis, there has been very little evidence showing its efficacy over placebo for outcomes surrounding pain, peak vertical force, and range of motion in enrolled canine patients.1

 

How does prolotherapy differ from platelet rich plasma and stem cell therapies?

While prolotherapy does elicit an inflammatory response resulting in growth factors and healing cascades, it requires injecting an irritating solution to produce such a response. This irritating solution can be painful during and after the injection, necessitating an anesthetic agent to be utilized in conjunction with the injection.

In platelet rich plasma and stem cell therapies, the body’s own cells are injected into the site of injury where they initiate the healing cascade at the affected tissue. The environment of the tissue is modulated through naturally occurring pathways facilitated by the cells being injected. Since platelet rich plasma and stem cell therapies utilize the body’s own cells and the injection of them creates minimal irritation, further damage of the tissue is avoided.

PRP Injection 2

References
1. J. Matthew Sherwood, James K. Roush, Laura J. Armbrust, and Walter C. Renberg (2017) Prospective Evaluation of Intra-Articular Dextrose Prolotherapy for Treatment of Osteoarthritis in Dogs. Journal of the American Animal Hospital Association: May/June 2017, Vol. 53, No. 3, pp. 135-142.
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The surprising facts about resident stem cells

What purpose do resident stem cells serve in the body? This is a fair but yet complicated question as our knowledge has only reached the “tip of the iceberg” with stem cell biology. Previously we have discussed adult stem cells, their use as a therapy, and made mention of the recruitment of resident stem cells to a site of injury. But what do we know about the stem cells that reside in the numerous tissues of the body? In today’s blog, we will explore the current scientific knowledge of resident stem cells, what they do (and do not do) and uncover some little facts that might even surprise you!

 

1.  What are resident stem cells?
Every individual (both two legged and four legged) has stem cells residing in their tissues and organs. Also referred to as adult stem cells, these cells are characterized by two very important attributes1:

1.  Self- renewal: the ability to divide without differentiation
2.  Multipotency: the capacity to specialize in different cell types

2.  Where can these resident stem cells be found?
Almost every tissue in the body has resident stem cells housed in what is called a “stem cell niche”. This niche is generally understood to be a “micro-environment” where stem cells reside and where they receive signals from other cells in the body to activate, self-renew or remain dormant2.Stem cell niches can be equated to an operator providing assistance. They receive “calls” from the tissue, direct the message to the appropriate “department” (stem cell) and determine the action that is needed for resolution (“pick up the call”-stem cell to activate/ differentiate, “set up meeting”- self renew or “send to voicemail”- stay dormant).

  • Bone Marrow
  • Adipose
  • Brain
  • Peripheral Blood
  • Blood Vessels
  • Skeletal Muscles
  • Skin
  • Teeth
  • Hair
  • Gut
  • Liver
  • Reproductive Tissues

3.  What purpose do resident stem cells serve in the body?
The primary role of resident stem cells is to maintain and repair the tissue in which they are found1. As discussed above, these stem cells are signaled through their niche to differentiate and respond to the area of damage.

4.  Why are degenerative conditions and injuries treated with platelet rich plasma and stem cell therapies if resident stem cells are already present near the injured tissue?
Chronic conditions such as arthritis and DJD have a multitude of factors that contribute to the progression of the disease, many of which are beyond the scope of this blog. While stem cells may be located near the area of injury, there are several reasons why they may not be renewing the damaged cells in the tissue. Hypothesized reasons for this include:

1.  Resident stem cells make up a very small number of cells in each tissue3. In the instance of a degenerative disease, the rate at which cells are replenished through resident stem cells can be suboptimal compared to what is necessary to fully repair the tissue. This constant demand for “repair mode” may also lead to the exhaustion of the regenerative potential of the tissue2.
2.  As the body ages, so do the communication pathways between the tissues and the resident stem cells. These communication pathways, which are influenced by growth factors, can become disrupted or dysregulated, which can lead to slowed/halted renewal (stem cells stay dormant and/or limited in numbers) or unregulated production (ex. cancer)2.Regenerative medicine shows great promise in benefiting tissues where these communication pathways and imbalances are present. Platelet Rich Plasma provides beneficial growth factors which aid in the recruitment of resident stem cells while stem cell treatments have the potential to restore tissue homeostasis and structure.

5.  What tissues have resident stem cells?
In the early days of research, few tissues were thought to have stem cells, which included bone marrow, fat, skin and muscle. Now, that list has grown exponentially to encompass1:

While more research is needed to fully understand the functions and purpose of resident stem cells, it is easy to see they are an important part of tissue biology and diseases. Stay tuned for our next blog where we will travel back in time to the early years of regenerative medicine!

1. NIH Stem Cell Information Home Page. In Stem Cell Information [World Wide Web site]. Bethesda, MD: National Institutes of Health, U.S. Department of Health and Human Services, 2016 [cited August 15, 2017] Available at < //stemcells.nih.gov/info/basics/7.htm>
2. Adv Exp Med Biol. 2010 ; 695: 155–168. doi:10.1007/978-1-4419-7037-4_11.
3. Adult mesenchymal stem cells and cell-based tissue engineering. R.S.Tuan, G. Boland and R.Tuli Arthritis Res Ther. 20025:32. https://doi.org/10.1186/ar614© BioMed Central Ltd 2003

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Physical Exam

ROM Testing 2Performing a systematic physical examination and visual observation of the patient’s mobility will provide an initial assessment on where the potential issue(s) may exist. A thorough orthopedic exam allows for palpation of the limbs and joints while moving them through their range of motion to draw attention to changes within the tissue and help assess if the patient seems painful. Additionally, it is important to complete a neurologic evaluation and consider running additional diagnostic tests to look for any underlying disease processes that could affect treatment options.

Pain Evaluation

According to the Summary of 2015 AAHA/AAFP Pain Management Guidelines for Dogs and Cats, the most accurate method for evaluating pain is through observing any changes in the pet’s behavior. A pain score is considered the fourth vital sign after temperature, pulse and respiration.1 A patient’s pain should be evaluated in the clinic and by the pet owner to paint a full picture of how the pet is acting.

Pet Owner

Feedback from the owner is vital in understanding where, the length of time and severity of how the pet has been affected to determine the next steps for evaluating if arthritis is present. He or she should be asked a series of questions about any changes in behavior and given a pain scale form to fill out based on whether it is an acute or chronic problem. This will provide valuable insight into the pet’s everyday activities and how they vary.

Standing Evaluation

Stance Analyzer Golden Retriever SmallGathering data on how a patient is bearing weight while standing can provide objective numbers to determine which limb or limbs are effected. It has been shown that bathroom scales can be used as a reliable way to measure static weight bearing in canines2; therefore, a free-standing platform with built-in sensors, such as the Stance Analyzer, can visually show where a potential lameness exists. This sort of tool takes up minimal floor space and can be a cost-effective option in helping obtain a diagnosis, as well as measuring patient outcomes. Recording this sort of information can help guide treatment plans and provide owners with a better understanding of the source of their pets’ complications.

Gait Analysis

Objectively measuring a patient’s gait can be performed via force plate or a commercially available portable walkway. Force plate is considered the gold standard for evaluating gait by calculating the ground reactive forces of a cat or dog while standing, walking or jogging over the plate. The portable walkway is a mat that allows a pet to stand, walk or jog providing information on gait symmetry, stride length and the amount of pressure placed on each paw. These types of devices are expensive and take up a lot of floor space, thus they are not as common of an option for general practice.

Imaging

It is very important to obtain a picture of the joints suspected of having osteoarthritis. Radiographs are most commonly taken to assess the bony changes associated with OA. MRI and CT offer additional diagnostic capabilities, though less commonly used to assess OA, with MRI showing how the soft tissues are involved, while CT can offer better detail for the bony changes in more complex joints.

Arthrocentesis

Collecting a sample of the fluid in a swollen joint or joints suspected of having arthritis can help rule out what is causing the swelling or pain, especially in younger patients, or in those with a more complicated clinical history. The color, consistency and cellular make-up of the synovial fluid can provide clues as to what changes are occurring within the joint and why.3

 

References

1. Epstein, M. et. al. (2015). 2015 AAHA/AAFP Pain Management Guidelines for Dogs and Cats. JAAHA, 51(2), 67-84. doi: http://dx.doi.org/10.5326/JAAHA-MS-7331.
2. Hyytiäinen, H.K. et. al. (2012). Use of bathroom scales in measuring asymmetry of hindlimb static weight bearing in dogs with osteoarthritis. Veterinary and Comparative Orthopaedics and Traumatology, 25(5), 390-396. doi: https://doi.org/10.3415/VCOT-11-09-0135.
3. Degner, D. (2014, August). Arthrocentesis in Dogs. Clinician’s Brief. Retrieved from https://www.cliniciansbrief.com/article/arthrocentesis-dogs.

 

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