Using Mesenchymal Stromal Cells For The Treatment of Spinal Cord Injuries

Using Mesenchymal Stromal Cells For The Treatment of Spinal Cord Injuries

Spinal cord injury (SCI) continues to be a significant cause of disability. In fact, it is estimated that annual SCIs account for nearly 18,000 injuries in the United States and between 250,000 and 500,000 injuries worldwide[1]. While the main cause of SCIs in the United States continues to be motor vehicle accidents, other contributors include falls, recreational accidents, and complications from medical procedures.

In their attempt to minimize damage after SCI, researchers have proposed several treatment options. This review conducted by Zoehler and Rebellato identifies cell therapy, and specifically treatment with mesenchymal stem cells (MSCs), as the primary form of neuroregenerative treatment for SCIs.

Research has shown that mammals are unable to regenerate nervous cell tissue in an area damaged as a result of a SCI, which means currently they will be subject to permanent disability after suffering such an injury.

Current treatments for SCIs have proven unable to repair the damage, rather they are used to relieve SCI-associated symptoms, including pressure and scarring, while also attempting to reduce hypoxia resulting from edema and hemorrhaging. One such treatment, spinal compression surgery, has shown to be successful at achieving these outcomes with results being much better if the surgery is completed within 24-hours of the SCI.

Another treatment currently used after SCI is methylprednisolone sodium succinate (MPSS) administered intravenously. In addition to inhibiting lipid peroxidation, MPSS inhibits post-traumatic spinal cord ischemia, supports aerobic energy metabolism, and attenuates neurofilament loss. However, because this treatment is associated with gastrointestinal bleeding and infection, it is recommended to be used with caution. 

While not yet fully understood, cell therapy – and specifically therapy using MSCs – has presented promising findings related to regenerating tissue after a SCI. It is widely believed that MSCs effectiveness is related to their ability to secrete different factors and biomolecules.

MSCs also reduce inflammation, which is important in this application because inflammation is known to be a secondary event after sustaining initial SCI.

The authors point out that a better understanding of the specific mechanisms related to the regenerative effects of MSCs used when treating SCI is required in order to develop future MSC-based treatments designed to address SCI in humans.  Currently, despite the recent increased focus on the use of cell therapy to treat SCI and central nervous system trauma, there is no consensus on a number of essential topics, including cell type, source, number of cells infusion pathways, and number of infusions to achieve this goal.

Zoehler and Rebellato also point out that it’s important to better understand how the reorganization of injured neural tissues associated with MSCS is related to the restoration of neural function.

Numerous animal model and human clinical trials have confirmed the regenerative and neuroprotective potential of MSCs without adverse effects during or after infusion. The authors close this review by highlighting that MSCs continue to demonstrate potential as an alternative for SCI therapy, primarily because the therapy is not limited by the time of injury and has shown measurable improvements in patients with complete and incomplete SCI.

Source:  Fracaro L, Zoehler B, Rebelatto CLK. Mesenchymal stromal cells as a choice for spinal cord injury treatment. Neuroimmunol Neuroinflammation 2020;7:1-12. http://dx.doi.org/10.20517/2347-8659.2019.009


[1] “Spinal cord injury – WHO | World Health Organization.” 19 Nov. 2013, https://www.who.int/news-room/fact-sheets/detail/spinal-cord-injury.

Can Regenerative Medicine Help Spinal Cord Injuries?

Can Regenerative Medicine Help Spinal Cord Injuries?

When someone sustains a spinal cord injury, they may believe there is little to be done in terms of treatment. In the past, treating spinal cord trauma has been focused on providing support to the patient and accommodating any limited capabilities caused by the injury. Treating spinal cord injuries often involves mobility aids, physical therapy, and daily medications. While these are all essential aspects of spinal trauma care, they do not make any significant improvement to the injury itself.

The Latest Research

New research shows that future treatment of spinal cord injuries could actually focus on resolving the symptoms caused by the injury and restoring certain functions within the spinal cord itself. A recent clinical study shows that there could potentially be a treatment for these kinds of injuries after all. A clinical trial out of Mayo Clinic has taken a look at the effect of regenerative medicine, also known as stem cell therapy, on patients with spinal cord injuries, and the results were promising.

The clinical trial, known as CELLTOP, used intrathecal injections of autologous adipose-derived stem cells to treat patients with traumatic or severe spinal cord damage. They found that when patients received these stem cells, they saw an improvement in certain symptoms associated with their spinal cord injury. This included motor and sensory function, with increased strength in fine muscle movement.

One patient in these trials who had sustained a grade A cervical spine injury was treated with stem cell therapy and saw an improvement in motor and sensory function. Another patient experienced an increase in their fine motor skills, with an improved ability to grip and pinch with his fingers.

How Does Stem Cell Therapy Work to Improve Spinal Cord Injuries? 

While clinical trials are still continuing, research shows the potential link between stem cells and spinal cord trauma. It may be found in how stem cells interact within the spinal cord microenvironment. In these clinical trials, stem cell therapy has been shown to potentially reverse the microenvironment and resolve certain symptoms of spinal cord injury.

When a spinal cord injury occurs, it results in complex pathophysiology. After the initial injury, there are microenvironmental changes that inhibit axonal regeneration. Stem cells can help reduce trophic support to an injured spinal cord’s microenvironment. This modulates the inflammatory response and suppresses cystic changes.

While many spinal cord injuries are still considered traumatic and severe, these CELLTOP clinical trials show promising treatment options in the future. Mayo Clinic is currently continuing this research to find how stem cell therapy can further benefit patients with spinal cord injuries. To learn more about how regenerative medicine can help spinal cord injuries, contact a care coordinator at Stemedix today!

Treating Spinal Cord Injuries with Intravenous Infusion of Auto Serum-Expanded Autologous Mesenchymal Stem Cells

Treating Spinal Cord Injuries with Intravenous Infusion of Auto Serum-Expanded Autologous Mesenchymal Stem Cells

Spinal cord injury (SCI) continues to be a significant cause of disability. In fact, it is estimated that annual SCIs account for nearly 18,000 injuries in the United States and between 250,000 and 500,000 injuries worldwide[1]. Additionally, an estimated 294,000 people in the United States are currently living with some form of SCI, with males accounting for nearly 80% of all SCI injuries[2].

Despite a large number of SCIs occurring each year, therapeutic treatment options remain limited and primarily ineffective. Recently, improvements in the understanding of the promising role stem cells play in the healing process have led to significant developments in improving healing and restoring function lost as a result of Spinal Cord Injuries; specifically, the therapeutic treatment of SCIs with mesenchymal stem cells (MSCs) in animal models has demonstrated promising results.

Building off of the success observed in previous studies, Honmou Et al.’s recent study (2021) sought to further explore the safety and feasibility of intravenous infusion of MSCs is SCI patients; the study also explored the patients’ functional status after receiving IV infusion of MSC.

Specifically, Honmou Et al.’s phase 2 study delivered a single infusion of autologous MSCs cultured in auto-serum, to 13 SCI patients. After infusion, the study assessed the feasibility and safety of this procedure over a six-month period by using the American Spinal Injury Association Impairment Scale (ASIA) and International Standards for Neurological Function Classification of Spinal Cord (ISCSCI-92). The researchers also used the Spinal Cord Independence Measure (SCIM-III) as a way to assess the ability of daily living after receiving MSCs infusion.

Although this was a small, early, unblinded, and uncontrolled study, the researchers point out that the intravenous infusion of autologous bone marrow-derived MSCs, expanded in auto-serum, into SCI patients appeared to be safe and feasible with none of the patients exhibiting abnormal cell growth or neurological deterioration. Additionally, and similar to what’s been observed in prior studies conducted on animal models, the findings appear to support the rapid improvement of neurological function within a few days after IV infusion. The researchers also pointed out this study had several limitations, including potential observer bias and potential improvements resulting from surgical interventions.

The researchers point out that although the specific mechanism for this observed improvement in neurological status is not clear, several studies suggest that secreted neurotrophic factors from MCSs might be associated with the rapid improvements. Additional studies have also demonstrated that IV infusion of MSCs in patients with SCIs might also encourage changes in gene expression that encourage functional improvements, an observation that was consistent with the findings of this study.

In conclusion, the authors reiterate that the observed safety, feasibility, and initial indications of functional improvement after MSC infusion support the importance of additional, larger future studies designed to examine potential efficiencies in patients with SCI. Source:  (2021, February 18). Intravenous Infusion of Auto Serum-expanded … – ScienceDirect.com. Retrieved March 23, 2021, from https://www.sciencedirect.com/science/article/pii/S0303846721000925#!


[1] “Spinal cord injury – WHO | World Health Organization.” 19 Nov. 2013, https://www.who.int/news-room/fact-sheets/detail/spinal-cord-injury.

[2] “(SCI) Facts and Figures at a Glance – National Spinal Cord Injury ….” https://www.nscisc.uab.edu/PublicDocuments/fact_figures_docs/Facts%202015.pdf.

What Is Spinal Stenosis?

What Is Spinal Stenosis?

Spinal stenosis occurs when the spaces within the spine narrow, resulting in pressure on the nerves running through the spinal column. The condition often develops in the lower back (lumbar stenosis) or neck (cervical stenosis). 

People with spinal stenosis may not experience any symptoms, while others have pain, muscle weakness, numbness, and tingling. The condition is typically a result of osteoarthritis, the wear-and-tear deterioration of joints that occurs over time. Some doctors may recommend surgery to create additional space for the nerves.

Spinal Stenosis Symptoms

The symptoms of spinal stenosis may vary based on where the issue is located. 

Symptoms of Cervical Stenosis

With stenosis of the upper spine or neck region, patients often experience:

  • Weakness in the extremities, such as a hand, foot, arm, or leg
  • Balance issues
  • Numbness or tingling in the extremities
  • Neck pain
  • Bowel or bladder issues in extreme cases

Symptoms of Lumbar Stenosis

When stenosis occurs in the lower back, patients may have:

  • Weakness or numbness in the foot or leg
  • Pain or cramping in one or both legs while walking or after long periods of standing
  • Back pain

Causes of Spinal Stenosis

Some people are naturally born with a narrow spinal canal, but in many cases, spinal stenosis is a result of outside factors that have caused the narrowing. Possible reasons for stenosis may include:

  • A herniated disk: The soft cushions between vertebrae often dry out and are less able to absorb shock over time. If a disk’s exterior cracks, the material may escape and put pressure on the nerves or spinal cord.
  • Bone overgrowth: Osteoarthritis is commonly associated with bone spurs, which can make their way into the spinal canal. Paget’s disease, a bone disorder, can also result in bone overgrowth.
  • Ligament thickening: The cords that hold the spine together may thicken over time, bulging into the spinal column and creating pressure on nerves.
  • Spinal injuries: Trauma caused by car accidents and other injuries can damage the vertebrae, leading to issues such as displaced bone or fractures that can impact the spinal canal. Also, the swelling of tissue following back surgery can put pressure on the nerves in the spine.
  • Tumors: Development of tumors in the spinal cord’s membranes can also occur, though they are uncommon. 

In addition to these causes, certain factors also increase a person’s risk for spinal stenosis. Being over the age of 50, experiencing a back injury, and having a congenital spinal deformity such as scoliosis are all considered risk factors. Genetic diseases that impact bone or muscle development can also lead to spinal stenosis. If you want to learn more then contact a care coordinator today!

Exploring the Role of Stem Cells in Spinal Surgery

Exploring the Role of Stem Cells in Spinal Surgery

Recent breakthroughs in the field of regenerative medicine continue to support the tremendous healing potential of stem cell therapy.  Until a few years ago, stem cell research was limited to only what could be gathered from the research gathered from embryonic stem cells; this research was limited by the well-documented ethical concerns surrounding the practice of harvesting stem cells from embryonic sources.

Fortunately, alternative – and less controversial – sources of stem cells, harvested primarily from autologous bone marrow and adipose tissue have demonstrated promise in treating many diseases ranging from autoimmune conditions to myocardial infarctions. 

Considering this, the ability of adult stem cells to undergo division and multipotent differentiation has garnered the attention of spinal surgeons and specialists around the world, specifically for the potential benefits of these stem cells in the treatment of a variety of spine issues related to neural damage, muscle trauma, disk degeneration as well as it potential in supporting bone and spine fusion.

Stem Cells in Spine Surgery

Although the rate of spinal surgery, and specifically lumbar, cervical and thoracolumbar fusions, has continued to rapidly increase over the last 20 year, there has not yet been a breakthrough in surgical technology that has consistently demonstrated the ability to reduce reoperation rates associated with these procedures; additionally, these procedures have demonstrated little success in reducing the issue of pseudoarthrosis in patients.

As a result, spinal surgeons have begun experimenting with using stem cells to support the process of bone growth and fusion. As stem cell research continued to evolve, the discoveries of the ability of mesenchymal stem cells (MSCs) harvested from bone marrow, adipose tissue, and skeletal muscle differentiate when cultivated in the correct microenvironment has led to the realization that these stem cells demonstrated a significant effect of the process of spinal fusion. 

Adding to the potential benefits of these stem cells are several animal model studies confirming the benefits of the much more available, and much easier harvested adipose-derived stem cell (ADSC).  In fact, several of these animal studies have confirmed similar fusion results observed when comparing MSCs and ADSCs.

Stem Cells in Disc Regeneration

Changes occurring in the discs of the spine and specifically starting in the second decade of life, contribute to decreased disc height that contributes to the impingement of nerves and the development of lower back pain consistent with Degenerative Disc Disease.

Until recently, treatment of Degenerative Disc Disease was limited to conservative management techniques, including work and lifestyle modifications, physical therapy, medication, and epidural injections, or surgery in the form of disc replacement or spinal fusion.

Although realizing the actual effects of stem cells therapy for treating this condition has been limited in humans (primarily due to concerns associated with the potential for an immune reaction to allogeneic stem cells in humans), several animal studies have demonstrated decreased disc degeneration as well as significant improvement in height and hydration of previously damaged discs.  In addition, small-scale studies in humans have demonstrated improvements in pain and disability within three months of stem cell treatment.

Considering this, Schroeder J et al. call for larger clinical trials designed to further explore the benefits associated with using stem cell therapy to treat Degenerative Disc Disease.

Stem Cells in Treatment of Spinal Cord Injury (SCI)

Spinal Cord Injury (SCI) resulting from damage to the spinal cord most often is the result of motor vehicle accidents, falls, or injuries occurring during sports, work, or in the home; currently, the World Health Organization (WHO) estimates that worldwide between 250,000 and 500,000 people suffer an SCI each year[1]

SCIs range in severity, but most often are accompanied by some degree of tissue damage and/or cell death.  As a result, spine surgeons have been exploring the potential of stem cell transplantation with the hope of supporting functional recovery after an SCI is sustained. 

There are several phases associated with SCI.  Regardless of the specific phase associated with an SCI, scientists have realized that creating a microenvironment that enhances neuron and axon regeneration appears to be the most desirable outcome of stem cell therapy.  It is hypothesized that this is best achieved by suppression of the inflammation that typically accompanies cell apoptosis and necrosis.

Although embryonic stem cells appear to provide greater differentiation than adult stem cells, the ethical concerns surrounding their use have limited further exploration of these potential benefits. However, to date, adult mesenchymal stem cells (MSCs) used in the treatment of SCI have not demonstrated immunologic reactions and have demonstrated the potential to promote axonal regeneration, suppress demyelination, induce nerve regeneration, and induce nerve regeneration.

Unfortunately, the in vivo differentiation of MSCs into neuron-like cells has been documented to be inefficient, meaning that MSCS is currently not capable of directly repopulating or physically restoring the tissue damaged in SCI. 

While there have since been studies exploring the transplantation of neural stem cells (NSC) that have demonstrated sensory and motor improvements after stem cell transplantation and when combined with other cell and growth factors, these improvements were not statistically significant. Considering this, the authors of this study indicate that it’s difficult to provide a definitive statement on the clinical potential of stem cell therapy for the treatment of SCI.

In conclusion, the authors point out that there are additional areas, including iatrogenic nerve and muscle injury resulting from spinal surgery, that have not yet been clinically addressed.  The authors also point out that greater standardization of in vitro experimentation and animal models may aid in the speed of translation of stem cell therapy in spinal surgery.

Source:  (n.d.). Stem cells for spine surgery – NCBI – NIH. Retrieved from https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4300930/


[1] “sheets/detail/spinal-cord-injury – WHO | World Health Organization.” 19 Nov. 2013, https://www.who.int/news-room/fact-sheets/detail/spinal-cord-injury.

Stem Cells Appear Safe for Treating Patients with Spinal Cord Injury

Stem Cells Appear Safe for Treating Patients with Spinal Cord Injury

Though spinal cord injury is relatively common, with the incidence continuing to grow, there is only one medication used to treat this injury, and it is limited in its effectiveness. Methylprednisolone also comes with serious health risks and must be employed in a short 8-hour therapeutic window.

Given the successes observed with stem cell treatments for other nervous system injuries and diseases, scientists have posited that stem cell therapy could offer new opportunities to help those with spinal cord injury. As such, researchers recently conducted a study to determine whether a certain type of stem cell has the potential to treat spinal cord injury and whether that treatment would be safe to use in patients. The results of the study were published in The Journal of Spinal Cord Medicine.

In their study, the scientists used what is referred to as intrathecal transplantation of autologous adipose-derived mesenchymal stem cells, which are stem cells that come from fat tissue. They used these stem cells in 14 patients with spinal cord injury and evaluated the impact of these stem cells on the nervous system and on motor performance, and also monitored patients for any unwanted side effects.

Researchers did not see significant changes in magnetic resonance imaging (MRI) results over the 8 months following stem cell transplantation, but they did observe improvements in motor scores, suggesting that the stem cells were therapeutically effective against spinal cord injury. Importantly, the intrathecal transplantation of stem cells in these patients was not associated with any serious adverse events. Based on these results, scientists recommend that stem cell protocols are further investigated for their potential to treat patients with spinal cord injury.

 

Reference

Hur, JW et al. (2016). Intrathecal transplantation of autologous adipose-derived mesenchymal stem cells for treating spinal cord injury: A human trial. The Journal of Spinal Cord Medicine, 39(6), 655-663.

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