As researchers continue to uncover potential health and medical benefits associated with the regenerative properties of stem cells, there is growing interest in the field of stem cell medicine and specifically for use as an alternative therapeutic treatment of pain.
Of particular recent interest in this area is the differentiation ability of stem cells classified as totipotent, pluripotent, and multipotent. Stem cells that can differentiate into and form cells and build organs are known as totipotent stem cells. Pluripotent stem cells are able to differentiate into various types of cells. Multipotent stem cells can differentiate into several limited forms of cells. Of the three different types, only multipotent stem cells are found as adult cells in the body, including in organs, placenta, and bone marrow.
Recently, stem cell transplantation has been used as an alternative treatment for pain associated with severe osteoarthritis, neuropathic pain, and intractable musculoskeletal pain that does not respond to traditional or conventional medication.
Osteoarthritis
Although stem cells are thought to be a potential treatment approach for repairing and regrowing cartilage required for treating severe osteoarthritis, to date, regeneration of damaged cartilage has proven to produce limited results. One of the significant issues associated with using stem cells to regenerate cartilage is that cartilage contains no blood vessels or nerves, making cartilage regenerations very difficult once it is damaged. Making the process even more difficult, cartilage regeneration can only occur when the entire layer of cartilage and the layer of bone directly below the cartilage is damaged.
As such, therapeutic stem cell treatment possibilities for osteoarthritis include individual or combination treatment(s) of surgical intervention, tissue engineering, and intra-articulation injection of cultured stem cells; of these possible treatment options, intra-articulation injection of cultured cell therapy would be the preferred method as it is the least minimally invasive and most convenient for clinical use.
There have been mixed reviews as to the effectiveness of these treatments and, to date, there have been no reliable and convincing clinical human students with a high level of evidence conducted specifically on the efficacy in functional improvements and cartilage repair surrounding the application of intra-articular stem cell injection therapy. Although some who have had this treatment expressed improvements.
Neuropathic Pain
Stem cells have demonstrated the ability to release neurotrophic factors that enhance the growth and survival potential of neurons, secrete anti-neuroinflammatory cytokines, and provides a cellular source for replacing injured neural cells; this makes the application of stem cells a prime option for regulating and potentially even reversing intractable neuropathic pain.
Studies have confirmed that relieving neuropathic pain is possible through the administering of stem cells, both through intravenous injection and when directly administered to a specific injured site. However, while stem cells do not need to make direct contact with injured cells to produce a neuroprotective effect, stem cells applied directly to an injured site, as opposed to those intravenously injected appeared to better target and relieve neuropathic pain associated with a specific area.
In addition, while a further clinical human study is required, animal models of both diabetic neuropathic pain and spinal cord injury demonstrate that stem cell therapy, and specifically mesenchymal stem cells (MSCs), demonstrated improved blood circulation and nerve conduction velocity, reduced pain, and regeneration of the affected nerve.
Intervertebral Disc Disease
Patients diagnosed with degenerative disc disease who were treated with MSCs injected directly into the nucleus pulposus, or inner core of the vertebral disc demonstrated a reduction in pain and disability comparable to spinal fusion surgery.
Research has yet to identify an adequate, effective dosage of stem cells and further research on specific stem cell type, dosage, safety, and implantation rate is required. As research into the use of stem cell therapy in pain medicine progresses, it is important to see the development of evidence-based standardized methods of treatment.
A recent open-label, single-arm, phase 1 clinical trial designed to evaluate the safety and tolerability of repeated intrathecal (IT) administration of autologous mesenchymal stem cells (MSCs) from bone marrow in patients with progressive multiple sclerosis demonstrated findings and benefits resulting in the initiation of an FDA-approved randomized, placebo-controlled and blinded phase II large group study to demine further efficacy of this procedure.
Multiple sclerosis, or MS, is a progressive condition where the body’s immune system attacks myelin, the protective sheath covering the nerves of the central nervous system, resulting in debilitating communication problems between the brain and the rest of the body.
While the specific cause of MS has yet to be determined, the disease itself is characterized by specific areas of inflammatory CNS demyelination that either regenerates or progresses into a chronic condition with accompanying loss of neurons, neuroglial cells, and glial scarring.
Roughly 10% to 15% of MS patients experience progressive symptoms from the onset of the disease, including motor weakness, paralysis, sensory dysfunction, loss of coordination, and cognitive decline.
Although there are immunosuppressive and immunomodulatory therapies that serve to slow the progression of MS, therapeutics designed to protect, repair, or regenerate neural tissue as a way of restoring neurological function do not currently exist. Considering that, mesenchymal stem cells gathered from bone marrow have demonstrated the ability to promote tissue repair through the secretion of paracrine factors.
Study Design and Findings
The treatment phase of this phase 1 trial, conducted at Tisch MS Research Center of New York, involved select participants with progressive MS receiving three separate IT injections of autologous mesenchymal stem cell-defined neural progenitors (MSC-NPs) spaced three months apart; each participant was then assessed the day of treatment, then the day, week, and month following each administration. As part of the post-treatment assessment, participants were assessed again three and six-month after receiving the third dose.
Analyzing the results of this study, researchers found no serious adverse effects or hospitalizations associated with this IT MSC-NP treatment; this included no specific incidents of chemical or infectious meningitis.
Brain MRI scans gathered during the course of this study demonstrated no changes and specifically were characterized by the absence of new or additional T2 lesions or related progressions associated with the patient’s MS. These findings led researchers to conclude that multiple IT administrations of MSC-NP’s are safe in the short-term and well-tolerated in participants with progressive MS.
Over the course of the study, all participants were strictly monitored for changes associated with clinical status. Assessment information gathered at the three and six-month post-treatment marks demonstrated that 75% of the subjects in this study demonstrated specific neurological improvement associated with this IT MSC-NP treatment when compared to established benchmarks, including neurological improvement associate with:
Expanded disability status scale (EDSS)
Timed 25-ft walk (T25FW)
MRC muscle strength scale
Bladder function
Key findings and observations contributing to this study include previous studies of experimental autoimmune encephalomyelitis (EAE) animal models of MS led to the experimental design of this study including multiple dosing of MSC-NPs (as opposed to single dosing).
When constructing this research study, researchers also determined that the intrathecal route of administration for cell delivery was important. While previous research has demonstrated administering bone marrow MSCs intravenously has proven to suppress EAE through immune response, intravenous administration has not demonstrated to cross the blood-brain barrier in amounts sufficient to directly impact and/or benefit the CNS; the IT route of administration appears to maximize the therapeutic potential to benefit the CNS and spinal cord.
This study concluded that IT therapy with MSC-NPS is safe and well-tolerated in patients with progressive MS and demonstrated a number of neurological benefits. As a result of this phase 1 trial, an initiation of FDA-approved randomized, placebo-controlled, and blinded phase II study in a larger group study to better determine efficacy in patients with progressive MS.
The ability for bone to naturally repair fractures and other common injuries have been well documented. However, research has consistently demonstrated that as they age, bone loses its ability to heal, repair, and fend off various bone diseases. In fact, each year, in the U.S. alone, there are over 2 million fragility-associated fractures with associated healthcare costs exceeding more than $20 billion dollars.
Currently, non-stem cell bone healing therapies including estrogen and related agonists, recombinant parathyroid hormone, supplements such as vitamin D and calcium exist, but with limitations and a number of potentially serious side effects.
Considering that the incidence of fracture and the associate rate of morbidity increase with age, current research is now examining other therapeutic options for the structural and functional restoration of bone, including the viability and of tissue engineering applications such as mesenchymal stem cells (MSCs) and bioscaffolding as potential solutions for the structural and functional restoration of bone.
Stem cells are generally used therapeutically in three distinct ways, including 1.) freshly isolated stem cells transplanted directly into tissue and undergo in vivo differentiation to become a desired cell type; 2.) the stem cell can be manipulated in vitro prior to being implanted; or 3.) circulating endogenous stem cells are recruited by cytokines to facilitate cell proliferation, migration, adhesion, and differentiation.
As researchers continue to explore using MSCs as part of therapeutic bone regeneration, it is generally accepted that MSC bone marrow density and quality decrease with age. In addition, a factor in determining the effectiveness of MSCs related to facilitating tissue repair is the ability for the stem cells to be directed to the site of injury, a process more commonly known as “homing”. A recent study using mice has demonstrated that MSCs appear to lose their homing ability rapidly while young MSCs demonstrate better homing ability, especially when compared to old MSCs. Considering this, future research must consider the age of both donor and recipient when determining the effectiveness of this strategy.
In addition to stem cells, bioscaffolds are also considered an essential component of the bone regeneration strategy, serving as the reservoir for multiple factors, the carrier for cells, the filler for the void space, and the template for bone regeneration. The ideal scaffold for bone tissue engineering has been identified as:
Showing no local and systemic toxic effects to the host tissue
Supporting normal cellular activity
Allowing cell adhesion, proliferation, extracellular matrix deposition, and inducting new bone formation
Prompting the formation of blood vessels after weeks of implantation.
Considering the above, several substrates have been identified as potential bioscaffolds to support improved regeneration of bone tissue, including decellularized extracellular matrix scaffolds, synthetic scaffolds (calcium phosphate-based bioactive ceramic scaffolds; metallic scaffolds (including metal scaffolds coated with growth factors and other bioactive factors); hybrid scaffolds combining two or more materials (metal-ceramic-poly hybrid scaffolds); natural and synthetic polymeric scaffolds; and nanomaterial-based scaffolds.
As research continues to explore the possibilities of new therapeutic approaches to bone healing provided through various tissue engineering applications, the use of MSCs and bioscaffolds continue to demonstrate potential benefits. Among the key areas requiring further study is the need to develop vascularization in engineered bone material. Bone and bone tissue has a rich vascular supply; while the recent study has demonstrated nanomaterials as having the potential to promote vascularization (without the aid of growth factors), further research and clinical trial are required.
Promising early research shows that when introduced into a brain injured by stroke, extracellular vesicles (EVs), also known as exosomes, a bioactive substance secreted by mesenchymal stem cells, have been associated with improved blood vessels creation, increased formation of neurons, and enhanced preservation of the neurological structure; these findings demonstrate a promising stem cell-derived stroke therapy that serves as an alternative approach to current stem cell infusion treatment options.
With nearly 14 million people suffering strokes each year, strokes continue to be the leading cause of physical disability among adults; between 25 percent and 50 percent of stroke survivors are left with significant and debilitating disabilities.
Because mesenchymal stem cells, or MSCs, secrete extracellular vesicles thought to reduce inflammation, enhance autophagy, and promote regeneration of damaged cells, researchers evaluating potential regenerative strategies for stroke-induced neurologic deficits have identified these MSC-derived EVs as a viable option for stroke therapy.
Although the reported beneficial effects of EV therapy has been observed in studies completed on animals, there is an increasing number of clinical studies currently being conducted on humans that suggest MSC EV stem cell therapy is a potentially safe and effective therapeutic option to improve outcomes in several various human applications.
Specifically, this EV-mediated therapy appears to offer an off-the-shelf treatment option that is potentially effective in crossing the blood-brain-barrier (BBB) while also avoiding cell-related problems, including the formation of tumors and infarcts resulting from vascular occlusions, or blood clots, consistent with those observed in acute ischemic stroke.
While there appears to be a promising upside to MSC EV therapy for the treatment of stroke, studies are on-going to discover the optimal therapeutic treatment of stroke patients. Some areas to continue researching are the optimal time and best mode of application of EVs in stroke patients (most stroke-related recovery occurs in the first few months following the stroke).
As research continues into the effectiveness of MSC-EV therapy for stroke, early indications are that EVs derived from mesenchymal stem cells could be a viable cell-free treatment option for patients recovering from a severe stroke.
Coronary artery disease (CAD) is the most common form of heart disease and the leading cause of death in the U.S. The condition develops when the arteries which deliver blood to the heart narrow and harden, caused by plaque buildup in their inner walls known as atherosclerosis. Left unaddressed, this condition can lead to a complete blockage of blood flow, which can result in heart attack, stroke, or blood clot.
There are several existing treatments available for CAD, including medications for controlling blood pressure and cholesterol, lifestyle changes, and coronary artery graft bypass surgery. The surgical procedure involves using blood vessels from other parts of the body to bypass damaged ones. Angioplasty may also be considered, in which the plaque is removed from arteries using a small balloon to push plaque away.
An Alternative Approach: Stem Cell Therapy
While conventional treatments are generally effective for treating CAD, they don’t address the underlying issue of plaque buildup. Stem cells, however, may help to eliminate plaque.
According to experts, inflammation plays a key role in the creation of plaques in the arteries. With their powerful anti-inflammatory properties, stem cells could help to prevent inflammation, and thus plaque, from building up in the arteries in the first place. The cells also have immunosuppressive and anti-angiogenic properties, which can help to combat existing plaque buildup and prevent further plaque from developing. Research indicates treating heart disease with stem cells is safe and can provide strong therapeutic outcomes.
In one study performed in the Netherlands, patients who were treated with bone marrow-derived stem cells experienced symptom relief and improvement in pain, as well as extreme reductions in artery blockages. Researchers suspect the stem cells either helped with the development of new blood vessels or aided in the removal of plaque in existing blood vessels.
Although stem cell therapy has yet to be adopted as a standard treatment for Coronary Artery Disease, it’s possible that in the future, it could be an alternative option that helps reduce surgeries and hospitalizations, prevents major cardiac events, and enhances the longevity and quality of life of many patients.
Many conditions may benefit from this regenerative medicine option and it is being researched and considered to help manage condition symptoms. To see if you are a candidate, please complete a contact form for a complimentary assessment.
Rheumatoid arthritis (RA) is a chronic inflammatory condition in which the immune system attacks healthy joint tissue. This abnormal immune response leads to inflammation, fluid buildup, swelling, and discomfort in the joints. RA is a chronic condition for which there is no cure, and due to the progressive nature of the disease, symptoms often worsen over time.
Current treatments for RA involve controlling the immune response to prevent further damage and alleviating joint pain. Yet, oftentimes, existing therapies fail to mitigate the damage joints have already sustained. Some research has been finding that there may be potential therapeutic effects with regenerative medicine, also known as stem cell therapy for Rheumatoid Arthritis.
Stem Cell Therapy for Rheumatoid Arthritis
Stem cells are the building blocks of virtually all specialized cells and tissue in the body. They can transform into many different cell types, and have regenerative and anti-inflammatory properties. Medical researchers have been exploring ways to leverage these powerful cells to help manage symptoms for autoimmune conditions, including Rheumatoid Arthritis.
As the cartilage between bones becomes inflamed and wears away, the joint and surrounding bone can become damaged, too. Mesenchymal stem cells (MSCs) can develop into bone and cartilage tissue, and when isolated and injected into affected joints, could help repair damage caused by RA.
Since RA is an inflammatory disease, it can lead to health issues beyond joint damage. Systemic inflammation, fever, weight loss, muscle weakness, and diseases of the heart and lungs can also occur over time. For this reason, combatting the widespread inflammation that occurs with the disease is critically important. According to research, MSCs can control inflammation by increasing regulatory T cells (RTCs), which help to prevent the immune system from attacking healthy tissue.
Additional study results have shown significantly lower levels of blood markers which indicate RA at one- and three-year intervals after stem cell therapy. In these trials, patients received intravenous infusions of MSCs to treat the systemic inflammation associated with RA. In addition to reduced body-wide inflammation, patients also experienced a reduction in symptoms and improvements in physical function.
Although there still has yet to be a definitive cure for RA, stem cell therapy has been researched as a potential option to:
Reduce joint inflammation and stiffness
Increase range of motion
Improve energy levels and reduce fatigue
Minimize joint pain and swelling
For patients interested in exploring new treatment options, MSCs may enhance a patient’s quality of life and alleviate some of the condition’s most debilitating symptoms. Contact a Care Coordinator today for a free assessment!
This website and its contents are not intended to treat, cure, diagnose, or prevent any disease. Stemedix, Inc. shall not be held liable for the medical claims made by patient testimonials or videos. They are not to be viewed as a guarantee for each individual. The efficacy for some products presented have not been confirmed by the Food and Drug Administration (FDA).
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