Heterogeneity of Mesenchymal Stem Cells in Cartilage Regeneration

Heterogeneity of Mesenchymal Stem Cells in Cartilage Regeneration

Articular cartilage, found on the surface of most musculoskeletal joints, distributes and transfers forces between bones and joints, provides a smooth surface for joint mobility, and plays an important role in human mobility. 

However, articular cartilage is also easily susceptible to damage, but difficult to repair itself on its own (primarily due to the fact it is mostly avascular). Over time, the inability of articular cartilage to repair itself leads to progressive joint pain, disfigurement, movement disorders, and ultimately osteoarthritis.

The CDC estimates that nearly 33 million Americans are currently affected by osteoarthritis, most often in the form of pain, stiffness, decreased mobility and range of motion, and swelling in the joints[1].

Current treatment methods, including microfracture technology, autologous or allogeneic cartilage transplantation, and autologous chondrocyte implantation (ACI) have demonstrated the ability to repair and regenerate fibrous cartilage, but not articular cartilage required for smooth, fluid, natural mobility.

To address this issue, recent research has focused on the efficacy of stem cells, and specifically mesenchymal stem cells (MSCs) found in bone marrow, adipose tissue, synovial membrane, and umbilical cord Wharton’s jelly, as potential therapeutic treatments for regeneration of articular cartilage. MSCs are particularly of interest due to their demonstrated abilities of self-renewal, multi-differentiation, and immunoregulation.

While the use of MSCs has demonstrated tremendous potential in the field of regenerative therapy, one notable drawback continues to be unstable or suboptimal results resulting from the heterogeneity of various mesenchymal stem cells.

Specifically, the stability and efficacy of MSCs appear to differ based on a number of factors, including the donor, the tissue source, and their ability for proliferation, differentiation, and immunoregulation.

For example, some of the key heterological differences highlighted in this review include the efficacy of MSCs based on donor’s age (with younger donors providing higher quality MSCs), Wharton’s Jelly MSCs showing greater prospects for application in cartilage regeneration than other MSCs, and differences within specific MSC subpopulations. 

The authors of this review acknowledge the potential of MSCs in repairing arterial cartilage, but also point out that there needs to be a deeper understanding of the heterogeneity of various MSCs in order to improve the efficiency of MSC-based therapies designed to repair arterial cartilage.  In addition, the authors also call for greater standardization in MSC isolation and harvesting methods among laboratories in order to provide better consistency with respect to results obtained from studies using MSCs.

Source:  “Heterogeneity of mesenchymal stem cells in cartilage regeneration.” 19 Mar. 2021, https://www.nature.com/articles/s41536-021-00122-6?elqTrackId=5517bd20493b470cb34fd0e8bc1f6ef9.


[1] “Osteoarthritis (OA) | Arthritis | CDC.” https://www.cdc.gov/arthritis/basics/osteoarthritis.htm.

Can Regenerative Medicine Help Manage Neurodegenerative Conditions?

Can Regenerative Medicine Help Manage Neurodegenerative Conditions?

Neurodegenerative conditions such as Alzheimer’s disease (AD), Parkinson’s disease (PD), and amyotrophic lateral sclerosis (ALS) occur when neuron populations begin to diminish. There is currently no cure for these types of diseases, though clinical trials to explore various treatment options are ongoing. In particular, regenerative medicine, also known as stem cell therapy, is being heavily researched and has shown remarkable progress in controlling these conditions. 

Types of Stem Cells

Stem cells serve as the foundation for every tissue and organ throughout the body. They are unspecialized but have the incredible ability to differentiate into virtually any cell type, as well as the power to self-renew.

Neurodegenerative conditions are characterized by neurons that progressively lose their function and structure, and eventually die off. Because stem cells are able to differentiate into multiple cell types, researchers have begun exploring whether they could replace or repair damaged neurons to control the progression of, or potentially even reverse the damage done by, these illnesses. Existing treatment options are limited, but many researchers are optimistic about stem cells’ potential.

Not all stem cells are the same. Here are the various types, some of which show more efficacy as a treatment for neurodegenerative disease than others:

  • Tissue-specific stem cells: These somewhat specialized stem cells can generate multiple organ-specific cells and are typically located in areas of the body that can self-replenish, such as the skin and blood.
  • Embryonic stem cells (ESCs): Located in blastocysts, ESCs are especially promising in neurodegenerative applications. Yet, they do pose some risks, including the risk of rejection. Due to their ability to differentiate into neurons, however, they continue to be studied as a potential therapy.
  • Induced Pluripotent Stem Cells (iPSCs): iPSCs are artificially derived from adult cells and programmed back to pluripotency, thereby allowing for an unlimited source of any cell type. While they are widely used for developing medications and disease modeling, further research must be done to refine the reprogramming process.
  • Mesenchymal Stem Cells (MSCs): MSCs can differentiate into several types of cells. Their self-renewal capabilities are far-reaching, making them an ideal candidate for therapies involving tissue repair. They may also be leveraged for cell transplantation in the treatment of neurodegenerative diseases.
  • Neural Stem Cells (NSCs): NSCs are derived from specific areas of the brain and are therefore specialized cells. They, too, are self-renewing and multipotent.

Types of Neurodegenerative Conditions Regenerative Medicine can Help Manage:

While researchers are uncovering new findings on how stem cells can treat neurodegenerative conditions nearly every day, there has already been progress. Here are some of the conditions stem cell therapy has been used to manage:

  • Parkinson’s Disease (PD): One hallmark characteristic of PD is the decline of dopamine, caused by the destruction of dopamine-producing brain cells. As dopamine decreases, symptoms such as muscle tremors, challenges with movement, and difficulty thinking arise. Now, researchers have found that stem-cell-derived dopaminergic neurons — in particular, those created through ESCs and iPSCs — could hold success in replacing the destroyed brain cells in individuals with PD.
  • Alzheimer’s Disease: Through the use of stem cell therapy, researchers at Columbia University have refined the protocol for a unique process of converting skin cells into brain cells. This option streamlines the process of creating neurons to replace those which have become damaged by Alzheimer’s disease. In their research, the cells were able to receive signals just as normal neurons would.
  • ALS: ALS has proven remarkably challenging to study, as there are many potential causes and therapies may therefore only be effective on specific patient populations. Moreover, the motor neurons, which are directly impacted by the condition, couldn’t be acquired in large enough numbers to study. Now, however, Harvard researchers have been able to derive mature cells that can be manipulated back into stem cells from ALS patients, opening up new doors for studying potential therapies to treat the condition.

While there is more ground to cover before stem cell therapy for neurodegenerative conditions can become mainstream, promising research is consistently being published. Moving forward, it’s likely that stem cells will hold the answer to viable management options for these and other challenging conditions.

Stem Cells Can Help Patients With MS

Stem Cells Can Help Patients With MS

As one of the most common neurodegenerative disorders, multiple sclerosis (MS) affects millions of patients. This progressive condition can cause everything from muscle weakness to double vision. Regenerative medicine is showing new potential when it comes to treating multiple sclerosis. Read on to learn more about how stem cells can help patients with MS.

What Happens During Multiple Sclerosis Flares?

In multiple sclerosis, a person’s immune system attacks the myelin of their nerve fibers. Myelin is a material that forms a protective layer, or sheath, around nerve fibers and shields them from damage. When the immune system attacks the myelin sheath, it causes inflammation and lesions that make it difficult for the brain to send signals throughout the rest of the body.

While there is no cure for multiple sclerosis, patients may undergo a wide variety of treatments to manage their symptoms. This may include physical therapy, immunosuppressants, steroids, and beta-blockers. Regenerative medicine, also known as stem cell therapy, is also showing great potential when it comes to managing multiple sclerosis and its symptoms.

Stem Cells and Multiple Sclerosis

Regenerative medicine works within the body at a cellular level, stimulating a healing response that can address certain symptoms of multiple sclerosis. Various types of stem cells have the potential to regenerate lost or damaged cells, including those that form the myelin sheath. This has the potential to improve the lives of MS patients, whose myelin layers have been damaged by inflammation. 

The following are three types of stem cells that can be used to treat multiple sclerosis:

Haematopoietic Stem Cells (HSCs)

Haematopoietic stem cells are adult stem cells found in the blood and bone marrow. These cells play an active role in immune function.

Mesenchymal Stem Cells (MSCs)

Mesenchymal stem cells (MSCs) are present in umbilical cords and fat tissue. These cells help promote the function of other stem cells throughout the body.

Neural Stem Cells (NSCs)

Neural stem cells are specialized stem cells that can repair the myelin in the brain. These cells can come from other stem cells, such as mesenchymal stem cells.

How Can Stem Cell Therapy Manage MS Symptoms?

Stem cell therapy can modulate the immune system, temporarily disabling the abnormal attacks on myelin tissue. When the immune system is no longer destroying healthy myelin cells surrounding nerve fibers, it can help slow the progression of multiple sclerosis conditions and potentially improve symptoms.

When patients receive stem cell therapy to treat their multiple sclerosis, they may experience some of the following benefits:

  • Reduction of muscle spasticity
  • Increased energy
  • Improved balance
  • Enhanced concentration
  • Decrease in visual disturbances
  • Improved range of motion
  • Reduction of muscle pain

While stem cell therapy has the potential to manage MS symptoms, it is still considered an experimental treatment and can not guarantee a cure. Although stem cell therapy is not FDA approved, there has been research to suggest it is safe and patients result in positive outcomes. Patients must have realistic expectations when choosing regenerative medicine for multiple sclerosis but it may be an option worth exploring. If you are interested in learning more about how Stem cells can help patients with MS, contact us today and speak with a care coordinator.

Physical Therapy for Pain Management

Physical Therapy for Pain Management

Up to 50 million Americans suffer from chronic or long-term pain. Missing work, the inability to do recreational activities, lack of concentration, and poor mental health are all side effects of living with chronic pain. However, one of the last things pain sufferers want to do may be the most effective treatment for chronic pain: exercise, and more specifically, physical therapy. Physical therapy for pain management can increase strength, mobility, and overall wellness for those suffering from chronic pain. 

Chronic Pain 

Doctors consider pain present for more than 12 weeks to be chronic pain. Some of the most common conditions causing chronic pain include:

Physical therapists typically focus on building strength and mobility when treating pain patients. Additionally, a physical therapist may work with patients to find safe, functional movements that don’t aggravate their pain.

How Physical Therapy Treats Pain

Physical therapists work to treat pain and its source. A physical therapist will look for muscle weakness or stiffness in areas that contribute to chronic pain symptoms. Then, they’ll treat your pain with exercises that help you move better and ease the pain. 

Most physical therapy sessions include a variety of training methods. 

Low-Impact Aerobic Exercises

Your physical therapist may choose an activity like cycling, walking, or swimming to amplify your heart rate, increase your range of motion, and provide fluid to your joints.

Strengthening Exercises

Your physical therapist may use low weights, resistance bands, weight machines, and bodyweight exercises (lunges and push-ups) to strengthen foundational muscles like your core or abdominal muscles.

Pain Relief Exercises

Pain relief exercises specifically target the source of your pain. For instance, a patient with knee pain may strengthen their leg muscles to support the joint better. 

Stretching

Gentle stretches are a fundamental part of physical therapy, as specific stretches can help to reduce pain, make muscle contraction more efficient, and work to release entrapped nerves.

Maintaining a consistent exercise routine can also help you retain the ability to move and function properly, rather than letting your pain render you immobile. 

Further Pain Support

When meeting with your physical therapist, discuss further treatment options to mitigate your pain. These treatments may include massage, heat and cold therapy, and transcutaneous electrical nerve stimulation (TENS), which many physical therapists offer in-office. 

Lack of movement and exercise worsens chronic pain. However, you can take charge of your pain symptoms by working with a physical therapist to build strength and mobility while lessening your chronic pain. Some patients are exploring stem cell therapy for chronic pain to help manage inflammation and pain. Mesenchymal stem cells (MSCs) are one specific type of stem cell that has the ability to differentiate into different types of cells. They are essentially the raw materials used to generate new tissues. This new alternative option may help patients manage their chronic pain along with conventional methods. If you are interested in learning more about physical therapy for pain management call us today and speak with. a care coordinator.

Efficacy of DMSA and EDTA in Chelation of Toxic Metals and Improvement of the Number of Stem Cells in Circulation

Efficacy of DMSA and EDTA in Chelation of Toxic Metals and Improvement of the Number of Stem Cells in Circulation

Metal toxicity, resulting from lead, mercury, aluminum, and arsenic, continues to be a significant public health concern and contributes to a number of serious health issues, including damage to the central and peripheral nervous systems, compromised kidney and liver function, and damage to the cardiovascular system. 

Specifically, toxic metals appear to contribute to oxidative stress in stem cells and endothelial progenitor cells (EPSs), the cells responsible for replenishing aging or damaged cells, and are an essential component for maintaining vasculature and neovascularization. The damage caused to these cells, as a result of metal toxicity, has directly contributed to vasoconstriction, hypertension, and altered gene expression.

Considering the established relationship between oxidative injury, endothelial cell dysfunction, and vascular disease, Mikirova et al. ‘s study examined the response of CD34-positive cells to chelation by DMSA. The study also compared the effectiveness of DMSA and EDTA in the chelation of toxic metals and the excretion of essential metals.

Mikirova et al. also share results related to the toxicity of lead and mercury to mesenchymal stem cells (MSCs), endothelial progenitor cells, and differentiated cells such as endothelial cells and fibroblasts. These results were obtained by comparing data obtained from 160 subjects who received oral DMSA chelation and 250 subjects who received intravenous EDTA chelation.

At the conclusion of this study, the authors were able to draw a number of conclusions, including:

  • Lead and mercury inhibit in vitro metabolism of MSCs and proliferation and adult differentiated cells, with MSCs demonstrating increased sensitivity to both lead and mercury.
  • DMSA demonstrated the ability to increase circulating CD34-positive cell numbers in vivo and is better at extracting lead and arsenic than EDTA – but is also more likely to increase extraction of certain essential minerals.
  • Removal of toxic metals significantly improved the number of stem cells and progenitor cells in circulation.

The authors also point out that DMSA offers improved results when compared to EDTA, for lead and arsenic chelation, but with a cost of higher extraction of essential minerals – including a fifty-five-fold increase in copper extraction (meaning copper levels must be monitored and supplemented for during chelation therapy). On the other hand, clearance of essential metals during chelation by EDTA was increased over twenty-fold for zinc and manganese.

Considering the findings of this study, the authors point out that these findings, along with data published in previous studies, provide some guidelines for the clinical use of DMSA and EDTA as chelating agents. 

Mikirova et al. conclude that chelation therapy demonstrates promise for repairing damage resulting from metal toxicity and for restoring circulating stem cell populations. The authors next plan to embark on a larger scale study with the hopes of gaining more data on changes in white cell and progenitor cell numbers before and after chelation therapy.

Source:  “Efficacy of oral DMSA and intravenous EDTA in chelation of toxic ….” https://www.transbiomedicine.com/translational-biomedicine/efficacy-of-oral-dmsa-and-intravenous-edta-in-chelation-of-toxic-metals-and-improvement-of-the-number-of-stem-progenitor-cells-in-circulation.pdf.

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