by admin | Jan 10, 2024 | Spinal Cord Injury, Stem Cell Research, Stem Cell Therapy
Spinal cord injury (SCI) is a devastating pathological condition affecting motor, sensory, and autonomic function. Additionally, recovery from a traumatic SCI (TSCI) is challenging due to the central nervous system’s limited capacity to regenerate cells, myelin, and neurological connections.
While traditional therapeutic treatments have proven ineffective in assisting in recovery, mesenchymal stem cells (MSCs) hold significant promise for the treatment of TSCIs.
As part of this systematic review, Montoto-Meijide et al. analyze the efficacy, safety, and therapeutic potential of MSC-based cell therapies in TSCI.
Specifically, the authors identified 22 studies fitting the objectives of this review, which provided the information needed to analyze changes in AIS (ASIA Impairment Scale) grade; to study changes in ASIA sensory and motor score; to evaluate chances in neurophysiological and urodynamic parameters; to identify changes in neuroimaging tests; and to test for the existence of adverse effects of MSC therapy.
Typically occurring as a result of trauma related to accidents or falls, TSCIs consist of two phases, a primary and a secondary phase. Considering the progression of SCI from the primary to secondary phase, the development of a therapeutic neuroprotective approach to prevent secondary injury continues to be a priority in both clinical and basic research.
Considering this, MSCs are currently one of the most promising therapeutic options for TCI, primarily due to their capacity for neuronal differentiation and regeneration, as well as their anti-apoptotic, anti-inflammatory, and angiogenic properties.
The 22 studies analyzed as part of this review included 463 patients. When analyzed in terms of the objectives listed above, Montoto-Meijide et al. reported that in controlled studies patients who received MSC therapy improved their AIS by at least one grade, with most studies also demonstrating improvement in sensory cores and motor scores.
In terms of neuroimaging evidence, the authors reported decreased lesion cavity size and decreased lesion hyperintensity. In addition, one-third of trials reported mild or moderate adverse effects related to the route of administration, and no reported serious treatment-related adverse effects.
The authors of this review reported that their results were consistent with the findings of other recent meta-analyses conducted by other researchers and were also consistent with studies that used a large number of patients but were not included in their review.
In addition, the authors also raise several interesting points that required further study, including determining the ideal stem cell type to use, identifying the most effective route and dose of administration, and finding out which degree and stage of development of the TSCL is most receptive to MSC therapy.
While MSC therapy continues to demonstrate promising potential results, Montoto-Meijide et al. also highlight future potential therapies currently in development. These therapies include gene therapies, nanomaterials, and neurostimulation combined with rehabilitation; all three of these potential treatments have shown promise when used in patients with SCI.
Limitations of this review include the relative newness of cell therapy in TSCI made it difficult to find relative studies and most of the studies used did not have a control group, were not randomized, showed low methodological quality, and lacked detail about the process and/or patient follow-up. Considering this, the authors emphasize the need for multi-center, randomized, and controlled trials with larger numbers of patients over a long period of time as a way to draw firm conclusions regarding this therapy.
Montoto-Meijide et al. conclude the positive changes in AIS grade and in ASIA sensory and motor scores, in addition to the short- and medium-term safety of this therapy, demonstrate the potential benefit of MSC therapy in TSCI patients.
Source: Montoto-Meijide R, Meijide-Faílde R, Díaz-Prado SM, Montoto-Marqués A. Mesenchymal Stem Cell Therapy in Traumatic Spinal Cord Injury: A Systematic Review. International Journal of Molecular Sciences. 2023; 24(14):11719. https://doi.org/10.3390/ijms241411719
by admin | Apr 21, 2023 | Stem Cell Therapy, Spinal Cord Injury, Stem Cell Research
The National Institute of Health estimates that nearly 250,000 people in the United States are currently living with a spinal cord injury (SCI). Most often a result of an accident, SCIs typically result in the loss of neurons and axonal damage resulting in the loss of function.
SCIs can be divided into two distinct phases, the initial physical injury and the secondary injury which typically occurs hours to days later. In most cases of SCI, damage to the axonal and tissue damage is caused by compression and/or contusion to the spinal cord. The secondary SCI injury occurs in the hours and days after the initial injury and is characterized by persistent inflammation, glial scar formation, demyelination of surrounding neurons, and death of cells. Over time, research has demonstrated that, in all aspects of secondary injury, the inflammatory response is the major cause and leads to widespread cell damage and lesion expansion.
Recent research has demonstrated that stem cells, including mesenchymal stem cells, neural stem/progenitor, and embryonic stem cells, possess anti-inflammatory properties and promote functional recovery after SCI by inducing macrophages M1/M2 phenotype transformation.
In this review, Cheng and He discuss the general features of macrophages in response to SCI, the phenotype, and function of macrophages in SCI, and the effects of stem cells on macrophage polarization and its role in stem cell-based therapies for SCI.
Macrophages accumulate in and around an SCI and play a very important role in neuroinflammation. Considering that recent research demonstrates the different, but important, contributions M1 and M2 macrophages make toward repairing tissue damage, this process is thought to be a promising therapeutic treatment for controlling the inflammation occurring after initial SCI.
According to this review, there are both positive and negative effects of macrophages on tissue repair and regeneration after an SCI. Interestingly, some studies show that infiltrating macrophages has harmful effects, especially in the early stages of an SCI. On the other hand, studies also indicated that macrophages have beneficial effects on tissue repair. These results included findings indicating that activated macrophages could provide a beneficial microenvironment that is good for the regeneration of sensory axons.
While the exact reason for the opposite effects of macrophages on the pathological process of SCI is not yet known, it’s thought to be because of the different phenotypes of macrophages – M1 (classical activation) and M2 (alternative activation).
Additionally, studies have demonstrated that M2 macrophages are important for efficient remyelination after CNS injury, while M1 macrophages hinder neurogenesis and inhibit neurite outgrowth and induce growth cone collapse of cortical neurons.
Considering these findings, the authors point out that polarization of macrophages to M2 is beneficial – and often preferred to M1- to facilitate the recovery after SCI. These findings have also demonstrated stem cell therapy to hold tremendous potential for therapeutic uses in the treatment/recovery after a spinal cord injury.
There is accumulating evidence indicating that the current preference of M2 macrophages compared to M1 macrophages correlates with remission of SCI in cases receiving SCI interventions including anti-inflammatory therapies and stem cells. The authors of this review conclude that while the exact process by which stem cells regulate macrophage polarization has yet to be determined, stem cells can alter macrophage polarization and promote functional recovery postinjury.
Source: “Anti-inflammatory effect of stem cells against spinal cord injury via | JN.” 13 Feb. 2017, https://www.dovepress.com/anti-inflammatory-effect-of-stem-cells-against-spinal-cord-injury-via–peer-reviewed-fulltext-article-JN.
by admin | Mar 29, 2023 | Spinal Cord Injury, Mesenchymal Stem Cells, Regenerative Medicine, Stem Cell Research, Stem Cell Therapy
The National Institute of Health estimates that nearly 250,000 people in the United States are currently living with a spinal cord injury (SCI). Most often a result of an accident, SCIs typically result in the loss of neurons and axonal damage resulting in the loss of function.
SCIs can be divided into two distinct phases, the initial physical injury and the secondary injury which typically occurs hours to days later. In most cases of SCI, damage to the axonal and tissue damage is caused by compression and/or contusion to the spinal cord. The secondary SCI injury occurs in the hours and days after the initial injury and is characterized by persistent inflammation, glial scar formation, demyelination of surrounding neurons, and death of cells. Over time, research has demonstrated that, in all aspects of secondary injury, the inflammatory response is the major cause and leads to widespread cell damage and lesion expansion.
Recent research has demonstrated that stem cells, including mesenchymal stem cells (MSCs), neural stem/progenitor, and embryonic stem cells, possess anti-inflammatory properties and promote functional recovery after SCI by inducing macrophages M1/M2 phenotype transformation.
In this review, Cheng and He discuss the general feature of macrophages in response to SCI, the phenotype, and function of macrophages in SCI, and the effects of stem cells on macrophage polarization and its role in stem cell-based therapies for SCI.
Macrophages accumulate in and around an SCI and play a very important role in neuroinflammation. Considering that recent research demonstrates the different, but important, contributions M1 and M2 macrophages make toward repairing tissue damage, this process is thought to be a promising therapeutic treatment for controlling the inflammation occurring after initial SCI.
According to this review, there are both positive and negative effects of macrophages on tissue repair and regeneration after an SCI. Interestingly, some studies show that infiltrating macrophages has harmful effects, especially in the early stages of an SCI. On the other hand, studies also indicated that macrophages have beneficial effects on tissue repair. These results included findings indicating that activated macrophages could provide a beneficial microenvironment that is good for the regeneration of sensory axons.
While the exact reason for the opposite effects of macrophages on the pathological process of SCI is not yet known, it’s thought to be because of the different phenotypes of macrophages – M1 (classical activation) and M2 (alternative activation).
Additionally, studies have demonstrated that M2 macrophages are important for efficient remyelination after CNS injury, while M1 macrophages hinder neurogenesis and inhibit neurite outgrowth and induce growth cone collapse of cortical neurons.
Considering these findings, the authors point out that polarization of macrophages to M2 is beneficial – and often preferred to M1- to facilitate the recovery after SCI. These findings have also demonstrated stem cell transplantation to hold tremendous potential for therapeutic uses in the treatment/recovery after SCI.
There is accumulating evidence indicating that the current preference of M2 macrophages compared to M1 macrophages correlates with remission of SCI in cases receiving SCI interventions including anti-inflammatory therapies and stem cells. The authors of this review conclude that while the exact process by which stem cells regulate macrophage polarization has yet to be determined, stem cells can alter macrophage polarization and promote functional recovery postinjury.
Source: “Anti-inflammatory effect of stem cells against spinal cord injury via | JN.” 13 Feb. 2017, https://www.dovepress.com/anti-inflammatory-effect-of-stem-cells-against-spinal-cord-injury-via–peer-reviewed-fulltext-article-JN.
by admin | Feb 15, 2023 | Spinal Cord Injury, Mesenchymal Stem Cells, 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.
by admin | Aug 5, 2022 | Spinal Cord Injury, Mesenchymal Stem Cells, 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.
by Stemedix | Jul 11, 2022 | Spinal Cord Injury, Stem Cell Therapy
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!
St. Petersburg, Florida
