by admin | Feb 8, 2024 | Spinal Cord Injury, Mesenchymal Stem Cells, Stem Cell Research, Stem Cell Therapy
Spinal cord injury is one of the most complicated and serious pathological impairments affecting the central nervous system. Since the human body is unable to regenerate and repair the spinal cord after injury, there is a high likelihood of suffering permanent damage and disability.
Often compounding the issue of SCI, secondary events occurring after the initial injury to the spinal cord significantly reduce cell migration and axonal regrowth and limit repair and regeneration.
Recently, transplantation of mesenchymal stem cells (MSCs) has been shown to promote the repair of injured spinal cord tissues in animal models. However, as Qu and Zhang highlight in this review, there remain many unanswered questions that are essential for improving the effects of this MSC therapy. As such, the authors focus this review on recent information about the behavior and function of MSCs in SCI, the function of biomaterials to direct the behavior of MSCs, and the attempt to emphasize combinational strategies such as tissue engineering for functional improvements of SCI.
There are studies showing that the migratory and homing capacities of MSCs are closely related to their engraftment and regeneration ability. Considering this, the authors highlight the importance of having MSCs migrate and integrate into host spinal cord tissue. Since MSC homing toward injured tissue is not an efficient process, and to ensure a more effective stem cell therapy outcome, it is important that these transplanted cells be introduced in a way that increases the migratory potential of healthy MSCs to the site of injured tissue.
Additionally, while transplanted cells have been identified adjacent to neurons after SCI, the surviving number of grafted and differentiated neurons was too small to be considered to contribute to functional recovery after SCI. However, data suggests that the ability of MSCs to secrete soluble factors or vesicles rather than engrafting and transdifferentiating might serve an important role in SCI repair.
The authors also point to studies that indicate MSC implantation could promote a therapeutic effect and functional recovery in experimental SCI animal models. The authors believe that this is a result of MSCs ability to differentiate into specialized neuronal and glial cell lineages after transplantation. While MSC transplantation has not yet been proven to be an effective and reliable therapy for SCI, additional studies need to be done before the therapy is utilized in clinical applications.
MSCs respond to the local environment in multiple ways and represent the most promising exosomes for neuropathic applications. Qu and Zhang conclude this review by calling for more intensive studies examining the potential benefits of combining MSCs with nerve tissue-engineered scaffolds to direct cell behaviors after SCI, including growth, migration, and differentiation.
Source: “Roles of Mesenchymal Stem Cells in Spinal Cord Injury – Hindawi.” https://www.hindawi.com/journals/sci/2017/5251313/.
by admin | Feb 8, 2024 | Osteoarthritis, Mesenchymal Stem Cells, Stem Cell Research, Stem Cell Therapy
Osteoarthritis (OA) is the most common form of arthritis and occurs as a result of the protective cartilage, found on the ends of the bones, degenerates over time. While OA can occur in any joint, it is most commonly found to occur in the hands, hips, spine, and knee.
An estimated 365 million people worldwide are currently living with some form of knee OA. Although there have been improvements in conventional treatment methods that have shown some benefit, there is no therapy or drug that can prevent or treat the development of OA in the knee.
Recent phase I/II trials using mesenchymal stromal cells (MSCs) derived from bone marrow (BM) and adipose tissue have demonstrated the feasibility, safety, and clinical and structural improvements in focal or diffuse disease.
Considering the findings of these phase I/II trials, Orrego et al. conducted this study to better assess the safety and efficacy of the intra-articular injection of single or repeated umbilical cord-derived (UC) MSCs in knee OA.
The target population of this study was individuals between the ages of 40-65 with symptomatic knee pain for at least 3 months with grade 1-3 Kellgren-Lawrence radiographic changes in the targeted knee, without meniscus rupture.
The authors divided participants of this study into three specific groups, a control group which received intra-articular knee injections of hyaluronic acid (HA) at baseline and 6 months; the MCS-2 group, which received UC-MSCs at baseline and 6 months; and the MSC-1 group, who received UC-MSCs at baseline followed by placebo injection at 6 months.
At the conclusion of this study’s 12 months follow-up period, Orrego et al. found that the group with repeated UC-MSC intra-articular injections, or MCS-2, experienced significant clinical changes in total WOMAC, pain component, and VAS when compared with the control group. The authors also found that only patients in the MSC groups experienced significant amelioration of pain and disability at 6 and 12 months. The authors also reported no safety signals were detected in the experimental groups as compared with the HA controls.
Considering these findings, the authors conclude that the use of MSCs produces anti-inflammatory properties in response to tissue damage or inflammation that demonstrates suppressive effects on the maturation of dendritic cells, macrophages, Natural Killer, and cytotoxic T-lymphocytes.
While these results appear promising, the authors point out that even if all MSC trials report a good safety record and improvements in cartilage quality, the use of autologous cell therapy does come with some limitations. Among these limitations include a dramatic decline of bone precursor cells when these cells are derived from bone marrow. Studies have also shown reduced chondrogenic activity of MSCs in cultures obtained from individuals with advanced forms of OA. For these reasons, and considering the findings in this study, the authors highlight that allogeneic sources of MSCs have been shown to express superior clonogenicity, migration, and paracrine capacities.
The authors conclude that the repeated UC-MSC dose strategy utilized in this study led to a favorable safety profile and improved clinical results for the treatment of long-term pain in knee OA patients.
Source: Jose Matas, Mario Orrego, Diego Amenabar, Catalina Infante, Rafael Tapia-Limonchi, Maria Ignacia Cadiz, Francisca Alcayaga-Miranda, Paz L. González, Emilio Muse, Maroun Khoury, Fernando E. Figueroa, Francisco Espinoza, Umbilical Cord-Derived Mesenchymal Stromal Cells (MSCs) for Knee Osteoarthritis: Repeated MSC Dosing Is Superior to a Single MSC Dose and to Hyaluronic Acid in a Controlled Randomized Phase I/II Trial, Stem Cells Translational Medicine, Volume 8, Issue 3, March 2019, Pages 215–224, https://doi.org/10.1002/sctm.18-0053
by admin | Jan 25, 2024 | Spinal Cord Injury, Mesenchymal Stem Cells, Stem Cell Research, Stem Cell Therapy
Spinal cord injury is a global term used to capture damage to the spinal cord resulting from trauma (typically in the form of car accidents, falls, or work-related injuries) or from disease or degenerative conditions.
Worldwide, it is estimated that up to 500,000 people suffer some type of spinal cord injury (SCI), with most resulting from car accidents, falls, or violence. The World Health Organization reports that people suffering from SCI are between two and five times more likely to die prematurely as a result of this injury.
To date, there have been limited advances in therapeutic treatment or correction related to SCI, with any therapeutic development focused on treatment of SCI-related symptoms as opposed to the condition itself.
In this study, Muthu et al. analyze evidence of the efficacy and safety of mesenchymal stem cell (MSC) therapy in human subjects with traumatic SCI and identify the therapy’s potential for the future management of SCI.
To analyze this evidence, the authors identified and reviewed studies evaluating the efficacy and safety of stem cell therapy for SCI. Specifically, Muthu et al. screened 321 research articles before narrowing this study down to 66 full-text reviews and finally identifying 19 studies that fit the criteria for this review.
These 19 studies involving 670 subjects demonstrated that those in the identified intervention groups showed statistically significant improvement in key measurement criteria, including the American Spine Injury Association (ASIA) impairment scale grade improvement, ASIA sensorimotor score, activities of daily living score, residual urine volume, bladder function, light touch, and pinprick response.
The authors also found that while no significant difference was noted in motor score or activities of daily living scores, and that the intervention group has significant increase in complications, no serious or permanent adverse events were reported.
Considering these findings, Muthu et al.’s analysis establishes the efficacy and safety of MSC transplantation in the specific areas highlighted above (improvements in AIS grade, ASIA sensory score, and bladder function) without major adverse events. The authors also call for further research to better understand standardized dosing, time, route of administration, and source of MSCs used for transplantation.
Source: Muthu S, Jeyaraman M, Gulati A, Arora A. Current evidence on mesenchymal stem cell therapy for traumatic spinal cord injury: systematic review and meta-analysis. Cytotherapy. 2021 Mar;23(3):186-197. doi: 10.1016/j.jcyt.2020.09.007. Epub 2020 Nov 9. PMID: 33183980.
by admin | Jan 18, 2024 | Multiple Sclerosis, Mesenchymal Stem Cells, Stem Cell Research, Stem Cell Therapy
Multiple sclerosis (MS) is a progressive autoimmune disease that affects the brain, spinal cord, and central nervous system (CNS). Affecting an estimated 3 million people worldwide, MS is typically characterized by an autoimmune response that results in inflammation, demyelination, and degeneration of axons.
Most patients who are diagnosed with MS demonstrate a disease progression characterized by periods of relapse and remission that can last for an extended duration.
There is no treatment that can yet address the various rates of MS progression. Additionally, current therapeutic approaches are designed to address the shortening of the duration of recovery following an attack, mitigating the progression of the disease, and attenuating the symptoms associated with MS.
Recently, mesenchymal stem cells (MSCs) have shown various ranges of effectiveness when used for treatment of autoimmune diseases in clinical trials. However, most of the trials utilizing MSCs for this purpose have been reported for a variety of reasons, including a low number of treated subjects, different doses used in the studies, the feasibility of autologous or allogeneic transplantation, and the unclear therapeutic window after the treatment effect.
Considering this, the purpose of Islam et al.’s systematic review and meta-analysis (SRMA) was to provide a comprehensive assessment of the effectiveness and safety of MSC therapy in individuals diagnosed with MS. To achieve this, the authors identified studies that reported on the efficacy and safety of MSC therapy in human patients with MS based on the changes in the Expanded Disability Status Scale (EDSS) score from baseline to follow-up period. This screening process resulted in a total of 30 studies being incorporated into the systematic review and 22 studies being included in the subsequent meta-analysis.
Islam et al. reported that, following MSC therapy, it was observed that 40.4% of the patients with MS experienced improvement; 32.8% of patients remained stable while 18.1% experienced a worsening of their condition. In terms of the safety of MSC therapy, the authors reported that while no major complications were observed, headaches (57.6%), fever (53.1%), urinary tract infections (23.9%), and respiratory tract infections (7.9%) were the most commonly reported adverse events.
While further research, the development of new technology, optimization of MSC doses, and larger clinical trials are needed to fully evaluate the use of MSC therapy in the treatment of MS, the authors conclude that the results of this SRMA indicate that MSC therapy seems to be an efficacious therapeutic strategy for treating patients with MS.
Source: Islam MA, Alam SS, Kundu S, Ahmed S, Sultana S, Patar A, Hossan T. Mesenchymal Stem Cell Therapy in Multiple Sclerosis: A Systematic Review and Meta-Analysis. Journal of Clinical Medicine. 2023; 12(19):6311. https://doi.org/10.3390/jcm12196311
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
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