Mesenchymal Stem Cells as a Spinal Cord Injury Therapy Opportunity

by admin | Feb 15, 2023 | Mesenchymal Stem Cells, Spinal Cord Injury, Stem Cell Research, Stem Cell Therapy

Spinal cord injury (SCI) often results in damage to the spinal cord or the nerves found within the spinal column. Currently estimated to affect over 17,000 new patients each year in the United States, with 81% of these patients being male, the most common causes of SCIs are motor vehicle accidents, falls, acts of violence, and sports/recreational activities.

Current SCI treatment methods are unable to support the regeneration of the spinal cord and often lead to permanent nerve damage that affects motor and sensory function. The nature of SCI injuries often leaves patients unable to function at pre-injury levels and results in significant impacts on issues related to physical, mental, and socioeconomic health.

As more is learned about the potential benefits of regenerative medicine in the regeneration and repair of damaged cells and tissue, mesenchymal stem cells (MSCs) have emerged as potential candidates for the therapy management of SCIs; primarily because of their ability to release bioactive factors, their antiapoptotic effects, ability to inhibit scaring, and their ability to produce angiogenic effects.

Fracaro et al.’s review provides information about the damage from primary and secondary events after SCI, traditional treatments, and results of pre-clinical and clinical trials examining the use of MSCs as an SCI-tissue regeneration strategy.

Before sustaining an SCI, a wide range of inflammatory cells – all except for microglia – are found in blood vessels and throughout the spinal cord. Upon injury, it is common to observe immediate neuronal and glial death at the site of the injury followed by the development of an inflammatory process in the vascular and medullary region; it is this secondary response that results in the deterioration of the spinal cord and a general worsening of the condition. In the weeks and months following injury, remaining neutrophils and lymphocytes are found in the intravascular region, inactivated microglia remain in white matter, and macrophages are found in gray matter.

Traditional SCI treatments have demonstrated an inability to completely regenerate nervous tissue. Most of these traditional treatment methods attempt to reduce side effects and protect injured nerve tissue. Commonly used SCI treatments frequently include decompression surgery to relieve pressure and reduce hypoxia and ischemia; intravenous application of methylprednisolone sodium succinate (MPSS) to inhibit lipid peroxidation; neuroprotective agents to reduce cell dysfunction and death; and electrostimulation as a way to inhibit inflammation and reduce secondary injuries.

Despite the different techniques mentioned above, cell-based therapy is the only promising treatment aimed at regeneration. Stromal cells, and specifically MSCs, have demonstrated the potential for self-regeneration, differentiation, and immunomodulation. Although research has yet to determine exactly how MSCs promote functional recovery after SCI, they are widely thought to work through secreting different factors and biomolecules. MSCs have also demonstrated the ability to reduce inflammation, which is a very common secondary event occurring after SCI trauma. 

The authors conclude this review by pointing out that a better understanding of the regenerative effects of stromal cells in the nervous system is required in order for the future development of cell-based therapies for patients with SCI.

Source: “Mesenchymal stromal cells as a choice for spinal cord injury treatment.” https://www.oaepublish.com/neurosciences/article/view/3329.

Using Mesenchymal Stromal Cells For The Treatment of Spinal Cord Injuries

by admin | Aug 5, 2022 | Mesenchymal Stem Cells, Spinal Cord Injury, Stem Cell Research, Stem Cell Therapy

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.

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

by admin | Apr 9, 2021 | Mesenchymal Stem Cells, Spinal Cord Injury, Stem Cell Research, Stem Cell Therapy

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.