Strokes, medically known as cerebrovascular accidents, are one of the leading causes of permanent disability worldwide. They occur when blood flow to a part of the brain is interrupted, either due to a blocked artery, known as an ischemic stroke, or a ruptured blood vessel, known as a hemorrhagic stroke. Ischemic strokes are the most common, accounting for about 85 percent of all strokes, while hemorrhagic strokes are less frequent but often more deadly. Strokes not only affect an individual’s health and independence but also entail high economic and healthcare costs. In fact, the projected cost of ischemic strokes is estimated to reach over $240 million by 2030.
The risk factors for strokes are varied. Some can be controlled, such as high blood pressure, while others, like age and family history, cannot. Men are at slightly higher risk, and the likelihood of a stroke increases with age. Symptoms depend on which part of the brain is affected but often include sudden weakness or numbness on one side of the body, difficulty speaking or understanding language, vision problems, dizziness, loss of balance, and severe headache. Immediate treatment is essential because the longer the brain goes without oxygen, the more damage occurs.
As part of this study, Moñivas et al. conducted a literature review, summarizing all ongoing clinical trials of MSCs for ischemic stroke.
Current Treatments and Their Limitations
Current stroke treatments primarily focus on the acute phase—the first hours to days after the event. In ischemic strokes, treatments aim to restore blood flow to the affected brain area as quickly as possible. This can be done with clot-dissolving medications or mechanical procedures, such as thrombectomy, in which the clot is physically removed. Following the acute phase, patients often rely on rehabilitation to recover lost abilities. While rehabilitation is critical and can help regain some function, it rarely results in full recovery, leaving many patients with lasting disabilities.
Because existing therapies cannot fully reverse the damage caused by stroke, researchers are exploring new treatment strategies that can repair injured brain tissue and improve long-term outcomes. Among these, stem cell-based cellular therapies have shown significant promise.
Mesenchymal Stem Cells and Their Potential
Mesenchymal stem cells, or MSCs, are a type of stem cell with the ability to transform into several different tissue types, including bone, cartilage, and fat. They are known for their low risk of immune rejection, making them suitable for therapeutic use. MSCs can be collected from adult tissues, such as bone marrow, fat, and connective tissue, as well as from fetal tissues, such as the umbilical cord or placenta. Bone marrow is the most commonly used source in research because the cells are relatively easy to isolate and expand.
MSCs are characterized by their ability to adhere to plastic surfaces in lab conditions, differentiate into multiple tissue types, and express specific surface markers. These cells are not only capable of regenerating damaged tissues but also release molecules that reduce inflammation, protect existing cells, and promote tissue repair. In neurological conditions such as ischemic stroke, MSCs may provide neuroprotective benefits, reduce cell death, and stimulate the regeneration of damaged brain tissue.
How MSCs Work in Stroke Treatment
When a stroke occurs, brain tissue is damaged due to a lack of oxygen and nutrients. Secondary events, such as excessive inflammation, oxidative stress, and other complications, can worsen this damage. MSCs can help modulate the immune response, reduce harmful inflammation, and promote cell survival. They release molecules that encourage the formation of new blood vessels, support neural repair, and even stimulate neurogenesis, the creation of new neurons. These properties make MSCs an attractive option for reducing stroke-related brain injury and improving recovery outcomes.
Animal studies have shown that MSCs can protect neurons, reduce cell death, and promote tissue regeneration after a stroke. Clinical trials in humans are now exploring whether these effects can be translated into actual improvements in patient function and quality of life. Most studies focus on the acute phase of ischemic stroke because early intervention is critical. The sooner damaged tissue is supported, the better the chances of minimizing long-term disability.
Autologous vs. Allogeneic MSCs
MSCs can be sourced from the patient’s own body (autologous) or from a donor (allogeneic). Autologous treatment requires time to harvest and process the cells, which may delay therapy during the critical early phase of stroke. Allogeneic MSCs, on the other hand, are ready for use and can be administered quickly, providing timely intervention in acute cases. Studies suggest that allogeneic MSCs may have a stronger ability to regulate the immune response and reduce inflammation than autologous MSCs. Both approaches are being investigated in clinical trials, but early availability makes allogeneic MSCs particularly appealing for acute stroke treatment.
Sources of MSCs in Clinical Trials
The choice of MSC source matters for treatment effectiveness and practicality. Umbilical cord-derived MSCs are widely used because they are abundant, easy to collect safely, and non-invasive for both donor and recipient. Bone marrow-derived MSCs are also commonly used due to their accessibility and established safety record. Fat tissue and other sources are being explored, but the key is obtaining enough viable cells for therapy while ensuring safety and ethical considerations.
Dosage and Administration
Determining the correct dosage of MSCs is critical. Too few cells may fail to produce the desired therapeutic effect, while too many could lead to complications. Clinical trials use different strategies, including weight-based dosing and fixed dosages, with most studies administering a single dose and some exploring multiple doses or dose escalation. Administration routes also vary, with intravenous injection being the most common. This method allows cells to circulate through the bloodstream, reaching injured tissues throughout the body, and is less invasive than direct brain injections, reducing the risk of complications.
Safety and Tolerance of MSC Therapy
Completed studies have shown a high safety profile for MSC therapy, with most patients tolerating treatment well and few adverse events reported. No tumor formation or severe immune reactions have been observed in trials using adult MSCs.
Evaluating Effectiveness
Alongside safety, clinical trials assess the effectiveness of MSC therapy in improving stroke outcomes. This involves monitoring neurological function, motor abilities, and overall recovery. Evidence from preclinical and early clinical studies suggests that MSCs may reduce brain damage, enhance functional recovery, and improve quality of life. However, further research is needed to determine the optimal dosage, route of administration, and patient selection criteria to maximize benefit.
Timing of Treatment
Time is a critical factor in stroke treatment. The acute phase, which occurs in the hours and days following a stroke, is when interventions can have the greatest impact. Rapid administration of MSCs during this window may help minimize brain damage and improve long-term recovery. Delayed treatment in the chronic phase is being explored, but it appears to offer fewer benefits than early intervention.
Challenges and Future Directions
Despite the promise of MSC therapy, challenges remain. Researchers need to establish standardized protocols for cell preparation, dosing, and administration. Identifying which patients are most likely to benefit from MSC therapy is also critical, as factors such as stroke location, severity, and the timing of intervention may influence outcomes. Long-term safety and efficacy data are still limited, so continued monitoring and rigorous clinical trials are essential.
Future research may also explore combining MSC therapy with other treatments, such as rehabilitation or pharmacological interventions, to enhance recovery. Advances in cell technology and understanding of MSC biology will likely improve the effectiveness of these therapies and expand their potential applications in neurological medicine.
Implications of MSC Therapy for Ischemic Stroke Recovery
Ischemic stroke remains a leading cause of disability and death, with current treatments providing only partial recovery. Mesenchymal stem cells offer a promising approach to improving outcomes by protecting brain tissue, reducing inflammation, and stimulating repair. Clinical trials are actively investigating the safety and effectiveness of MSC therapy, with early results showing a high safety profile and potential benefits for patients.
While more research is needed to determine the optimal dosage, timing, route of administration, and patient selection, MSC therapy represents a promising advancement in stroke treatment. Prioritizing early intervention, patient safety, and careful evaluation of outcomes will be key to making stem cell therapy a reliable and effective option for people affected by ischemic stroke.
As the field progresses, MSCs may offer a new avenue for recovery, helping stroke survivors regain function, improve quality of life, and reduce the long-term burden of this devastating condition. Continued clinical research will be essential in translating the promising potential of stem cells into practical, accessible therapies for patients worldwide.
Source: Moñivas Gallego, E., & Zurita Castillo, M. (2024). Mesenchymal stem cell therapy in ischemic stroke trials: A systematic review. Regenerative Therapy, 27, 301–306. https://doi.org/10.1016/j.reth.2024.03.026
St. Petersburg, Florida
