Umbilical Cord-Derived Mesenchymal Stromal Cells (MSCs) for Knee Osteoarthritis

Umbilical Cord-Derived Mesenchymal Stromal Cells (MSCs) for Knee Osteoarthritis

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

6 Surprising Risk Factors for Erectile Dysfunction

6 Surprising Risk Factors for Erectile Dysfunction

In the United States, about 30 million men have some form of erectile dysfunction, according to research conducted by the National Institute of Diabetes and Digestive and Kidney Diseases. Erectile dysfunction can occur in men of any age, though it’s most common in those who are older. Despite this, it’s not a normal part of aging.  There are many causes of erectile dysfunction, from emotional to physical. However, most people are unaware of a few risk factors that could affect your chances of developing this condition. 

Understanding Erectile Dysfunction

Erectile dysfunction is a condition in which you are not able to get or maintain an erection firm enough for sexual intercourse. It can be a long-term or short-term problem. 

There are a few types of erectile dysfunction. One type is vascular erectile dysfunction, which results from issues with the blood vessels that send blood to the penis or the valves that hold blood. This is the most common form of erectile dysfunction. 

Neurogenic erectile dysfunction occurs as a result of nerve problems that stop signals from traveling from your brain to your penis. It can occur after trauma, radiation therapy, or conditions like spinal stenosis and multiple sclerosis. 

Hormonal erectile dysfunction occurs when you experience testosterone deficiencies, while psychogenic erectile dysfunction involves psychological causes. 

Surprising Risk Factors for Erectile Dysfunction 

Most men are aware that blood pressure issues, antidepressants, and even drinking alcohol can cause erectile dysfunction. Still, there are some surprising factors that can make your chances of dealing with this problem more likely. 

1. Sleep Apnea

Sleep apnea is a condition in which your breathing stops and restarts many times as you sleep. This irregularity leads to poor rest. Scientists have noticed that men who have sleep apnea have a higher risk of developing erectile dysfunction. 

The reason is not entirely clear, but it could be because the lack of sleep leads to dips in testosterone levels. Sleep apnea also restricts oxygen. Testosterone and oxygen are both crucial for maintaining healthy erections. 

Sleep apnea also leads to fatigue and potentially higher stress levels, all of which impact sexual function. Scientists have found that treating obstructive sleep apnea can also help erectile dysfunction symptoms. 

2. High Cholesterol

Having high blood cholesterol levels could also put you at a higher risk of developing erectile dysfunction. Perhaps the most common cause is the narrowing of blood vessels, also called atherosclerosis. High cholesterol levels can make this more likely to occur. 

Cholesterol is a fat-like substance in the blood that your cell membranes need and that helps produce certain hormones, bile acids, and vitamin D. At high levels, however, cholesterol builds up in artery walls and causes plaque, which narrows them. 

When that occurs, your penis doesn’t receive the amount of blood it needs to get and maintain an erection. 

3. Cycling

Although maintaining an active lifestyle tends to help with erectile dysfunction, cycling could be causing more harm than good. 

Hard bicycle seats often press on the perineum, which is the area between the scrotum and the anus, causing a compression of blood vessels. The compression makes it more difficult for the penis to get the needed blood flow. 

Scientists recommend using a softer seat or taking shorter rides to prevent the problem. Make sure to speak with your doctor about this if you suspect cycling could be causing erectile dysfunction issues. 

4. Canned Foods

Perhaps one of the most surprising risk factors of erectile dysfunction is the frequent eating of canned foods. Cans that hold food often contain the chemical bisphenol-A, also called BPA. BPA can affect your hormones, stimulating the production of female sex hormones and suppressing male sex hormones. 

5. Certain Medications

Lots of medications have the potential to affect sexual function, especially in men. This is because they can interfere with hormone pathways. 

One of these types of medications is selective serotonin reuptake inhibitors (SSRIs). These medications are antidepressants that function by increasing the levels of serotonin in the body, elevating your mood. The problem is that serotonin decreases sex drive. 

Blood pressure medications may also affect sexual function. Diuretics or ACE inhibitors decrease the blood flow that reaches the penis, making an erection more difficult to achieve. 

Other medications that could affect sexual function are those that treat Parkinson’s disease, antihistamines, and even non-steroidal anti-inflammatory disease. It is always a good idea to speak with your doctor about the side effects of any medications you take and to work with them to find alternatives. 

6. Leading a Sedentary Lifestyle

Another factor that can put you at risk of developing erectile dysfunction is leading a sedentary lifestyle. Being sedentary can cause decreased blood flow. Not leading an active life also makes it harder for your heart to function at its best. 

Even moderate exercise stimulates your body to produce nitric oxide, which is a short-lasting chemical that keeps your arteries open, including the ones that allow blood to flow into your penis. 

A sedentary lifestyle is associated with higher levels of fat in the body. The more fat you have, the more estrogen your body is likely to produce, which means your testosterone levels dip. It can also lead to a higher risk of developing diabetes, which impacts insulin resistance and makes the development of erectile dysfunction more likely.

Treating Erectile Dysfunction

Struggling with erectile dysfunction can affect your self-esteem, moods, and relationships. If you are dealing with this issue, it’s essential to reach out to your doctor for help. 

One option that offers the chance to get relief from erectile dysfunction is regenerative medicine. Regenerative medicine treatments like stem cell therapy focus on doing more than just treating the symptoms of the condition: they can help to treat the underlying problem that led to erectile dysfunction issues in the first place. 

If you are dealing with erectile dysfunction, consider asking your doctor about regenerative medicine. With these minimally invasive treatments, you could allow your body to start healing itself.

Treating Psoriasis Using Stem Cell Therapy

Treating Psoriasis Using Stem Cell Therapy

Characterized by scaly white or erythematous plaques, psoriasis is a chronic autoimmune dermatological disease most often appearing on the scalp, genitalia, lumbosacral area, and extensor surfaces of the limbs.

Affecting an estimated 125 million people worldwide, the condition most commonly is observed in those between the ages of 15 and 25 years of age.

The most recent advancements in the development of biological treatment have revolutionized the treatment of the condition for those with moderate to severe psoriasis, achieving clear or nearly clear skin with long-term success.

However, these treatments in their current form have not been proven to cure psoriasis completely. Additionally, a growing number of those suffering from severe psoriasis are not responding to these current therapeutic treatment options.

Recently, stem cell therapy, including regulatory T-cells, hematopoietic stem cell transplantation, and mesenchymal stromal cells (MSCs) have been used in patients with recalcitrant psoriasis.  In this review, Naik discusses stem cell treatment options available for psoriasis. 

Regulatory T-cells, or Tregs, regulate or suppress other immunocytes by modulating their responses to the endogenous environment and antigens, which helps to avoid autoimmune reactions and chronic inflammation. Several treatments for psoriasis, including many biologics currently being used, appear to increase the number of Tregs and their performance in patients with psoriasis.  This finding led Naik to conclude that, despite their high cost, Treg-based therapies may have the ability to interfere with the pathogenesis of psoriasis.

MSCs have been found to have a significant role in adaptive immunity. This immune-enhancing activity typically occurs in partnership with a number of immune cells, including neutrophils, dendritic cells, monocytes, natural killer cells, macrophages, B-cells, and T-cells. While several Phase I and II studies have not demonstrated significant toxicity, the author calls for more extensive controlled trials to better understand the efficacy and long-term safety of MSCs in this application.

The favorable results observed when using hematopoietic stem cells (HSCT) in a wide range of autoimmune conditions, including lymphoma, leukemia, lupus, diabetes, rheumatoid arthritis, and multiple sclerosis, led to interest in using these cells in patients with psoriasis. Interestingly, improvements in psoriasis have been observed in patients who have undergone allogeneic (rather than autologous) HSCT, suggesting that hematopoietic stem cells could contribute as a primary cause of psoriasis.

Naik concludes that the application of stem cells in the treatment of psoriasis raises hope for the development of a safe and effective therapy for those suffering from severe forms of the condition. While more data is required before clinical application, MSCs could be a promising therapy for the treatment of psoriasis. 

Source: Naik PP. Stem cell therapy as a potential treatment option for psoriasis. An Bras Dermatol. 2022;97(4):471-477. doi:10.1016/j.abd.2021.10.002

Exploring the Potential of Stem Cell Therapy in Addressing the Challenges of Pancreatitis

Exploring the Potential of Stem Cell Therapy in Addressing the Challenges of Pancreatitis

Acute and chronic pancreatitis are associated with local and systemic inflammation that is linked to a host of serious health issues. A result of the digestive juices and enzymes attacking the pancreas, pancreatitis currently has no definite treatment. 

Currently, it is estimated that over 6 million people worldwide are afflicted by acute or chronic pancreatitis with the number of diagnoses appearing to be steadily increasing.

The rising interest in stem cell therapy being used to potentially treat a wide variety of other diseases has led to interest in exploring it as a way to aid in the treatment of both acute and chronic pancreatitis. 

As part of this review, Chela et al. examine numerous studies using commonly used stem cells to explore their promise in the treatment of pancreatitis.

A number of studies are utilizing stem cells to repair and replace tissue damaged as a result of numerous gastrointestinal diseases, including acute and chronic pancreatitis. In the case of using stem cells, and specifically mesenchymal stem cells (MSCs), to treat pancreatitis, researchers are interested in the ability of these stem cells to regenerate damaged cells and to influence the immunological and inflammatory response resulting from this condition.  

A significant issue that has stymied progress in the ability of the pancreas to self-repair and regenerate when affected by pancreatitis is the perceived lack of stem cells found specifically in the tissue of the pancreas. While there has been conflicting research into whether or not stem cells exist in pancreatic tissue, the research reviewed by the authors indicates that there appears to be a tiny amount of stem cells located within pancreatic tissue.

Considering this and considering that additional research indicates that other stem cells found in the pancreas appear to originate from bone marrow (BM), the authors believe the ability of MSCs’ ability to differentiate will support the healing of the pancreas; these include stem cell sources from BM, adipose tissue, umbilical cord, and induced pluripotent stem cells (iPSCs).

Source: “Stem cell therapy: a potential for the perils of pancreatitis – PMC – NCBI.” https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7433995/.

Using Mesenchymal Stem Cell Therapy for Traumatic Spinal Cord Injury

Using Mesenchymal Stem Cell Therapy for Traumatic Spinal Cord Injury

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.

Exploring Cell Therapy for Neuropathic Pain

Exploring Cell Therapy for Neuropathic Pain

Neuropathic pain (NP) occurs when the nerves located either inside or outside of the brain and spinal cord are damaged by a lesion or a condition. To date, pharmacological and surgical treatments to address NP have focused on providing symptomatic relief without treating the underlying cause of the condition. These treatment approaches have not been overwhelmingly successful with over 50% of NP patients attaining adequate pain relief.

Recently, an increasing amount of pre-clinical and clinical research has demonstrated cell transplantation-based therapy for NP to be a promising treatment alternative.  

In this review, Yin et al. summarize the use of cell grafts for the treatment of NP, synthesize the latest advances and adverse effects, and discuss possible mechanisms to further the development of cell transplant-based therapies for NP. 

Neural stem cells (NSCs) demonstrate the ability to divide, self-renew, and differentiate into neurons, astrocytes, and oligodendrocytes; they are also present in a wide array of tissues throughout the body. Considering they are capable of differentiating into neurons and glial, NSCs are considered an ideal candidate cell for replacing damaged nerve cells and delivering trophic factors to the site of lesions contributing to NP. Additional studies have demonstrated NSCs ability to regenerate nerves, offer neuroprotective effects, and secrete a number of factors that enhance the survival of motor and sensory neurons. NSCs transplantation coils also ease NP caused by peripheral nerve injury, a potential benefit that has been observed in animal models.

Olfactory ensheathing cells (OECs) are glial cells that surround and enclose the olfactory nerve bundle and possess the unique ability to transgress the peripheral nervous system (PNS) and central nervous system (CNS). Considering OECs have been shown to have neuro-regenerative functions, they are also considered to be a good choice for treating nerve injury and NP. Studies using animal models have confirmed that OECs transplantation could promote motor recovery and mitigate pain. Although OECs have good prospects of being used for treating NP, the authors call for additional research with longer observation time to verify their long-term effects and safety.

Mesenchymal stem cells (MSCs) can be obtained from a wide variety of sources and can be induced to differentiate into endoderm, mesoderm, and ectoderm cell lines. MSCs are often used for the treatment of diseases involving neuroinflammatory components and have been shown in animal studies to potentially alleviate NP symptoms. 

Other cell therapies currently being evaluated for use as a treatment for NP include bone marrow mononuclear cells, GABAergic cells, and genetically modified cells. 

The authors conclude that, despite the small number of clinical studies and the lack of systematic evidence, cell therapy as a treatment alternative for NP should be further explored. Specifically, further research should examine the optimal transplantation route, transplantation timing, number of transplanted cells, and transplantation survival rate.


Source:  “Cell therapy for neuropathic pain – Frontiers.” 27 Feb. 2023, https://www.frontiersin.org/articles/10.3389/fnmol.2023.1119223.

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