Regenerative Medicine Using Mesenchymal Stem Cells for the Treatment of Liver Disease
Liver disease accounts for nearly two million deaths annually and is responsible for 4% of all deaths (1 out of every 25 deaths worldwide); approximately two-thirds of all liver-related deaths occur in men.
Most forms of chronic liver disease result from viral infections, alcohol abuse, or metabolic disorders and eventually result in cirrhosis and liver failure. The only effective treatment for end-stage cirrhosis is liver transplantation. Unfortunately, considering organ shortages and the high cost associated with this type of medical procedure, liver transplants are not available in many countries.
Stem cell transplantation, specifically transplantation using mesenchymal stem cells (MSCs), has been increasingly used as a potential treatment strategy for a host of diseases, including for treating chronic liver disease.
As part of this review, Kang et al. discuss the therapeutic effects of MSCs in liver diseases to address questions regarding their efficacy and safety, evaluate recent advances in this area, and consider the potential risks and challenges in the use of MSC-based therapies for liver disease.
When considering the therapeutic effects of MSC therapy in chronic liver disease, the authors conclude that this treatment has shown to be effective, primarily due to their immunomodulation, differentiation, and antifibrotic properties exhibited by MSCs. The authors also point out that although the safety and therapeutic effects of MSC therapy have been observed in several clinical studies, to date the therapy has demonstrated only modest improvements in treating liver disease. Kang et al. attribute this modest improvement, in part, to the current limited feasibility of transplanted cells.
The authors provide a detailed review of the strategies that have been utilized to improve the effects of MSC transplantation, including tissue engineering, preconditioning, genetic engineering, and using extracellular vesicles as cell-free therapy, and summarize the future potential of each of these as ways to improve MSC transplantation.
Kang et al. also highlight several problems that must be considered and addressed before MSCs are fully accepted as clinical therapeutic treatment options for chronic liver disease; these problems include the potential for carcinogenesis and viral transmission. For example, previous animal studies have demonstrated a relationship between the development of sarcoma and the number of passages. While this has not been directly observed in clinical trials involving human MSCs, the follow-up period was too short to allow for observed evidence of this development. As a result, the authors call for a detailed study into the chromosomal integrity before MSC transplantation to ensure the safety of the procedure.
In addition to the potential for tumor cell growth, allotransplantation of MSC cells may involve the risk of viral transmission to the patients. As a result, the authors indicate that both MSC recipients and donors may need to be screened for the presence of specific viruses, including parvovirus B19, herpes simplex virus, and cytomegalovirus.
The authors conclude that the prospects of MSC-based cell therapy for treating chronic liver disease will be determined by standardizing the cell source, culture conditions, administration route, and the outcomes of future large-scale clinical trials.
Source: “Mesenchymal Stem Cells for the Treatment of Liver Disease – NCBI.” https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7234888/.
A Review of Clinical Trials for Multiple Sclerosis with Mesenchymal Stem Cell Therapy
Multiple sclerosis (MS) is a progressive auto-immune disease that affects the central nervous system (CNS). Currently, it is estimated that nearly 2 million people worldwide are affected by MS.
Characterized by the body attacking the myelin (the protective sheath that covers the nerve fibers), MS causes communication issues between the brain and the rest of the body. As the nerves continue to deteriorate, the condition can cause permanent damage.
Currently, there is no pharmaceutical treatment for MS, only medications that treat the symptoms of the condition.
In the field of regenerative medicine, mesenchymal stem cells (MSCs) have emerged as a candidate that could potentially treat a number of diseases, including MS. Specifically, MSCs have anti-inflammatory effects and have demonstrated the ability to differentiate in order to target the overactivity and self-antigen attacks observed in the development and progression of MS.
As part of this review, Alanazi et al. reviewed a number of clinical trials that have utilized MSCs isolated from a variety of sources, including peripheral blood, bone marrow (BM-MSCs), adipose tissue (AD-MSCs), umbilical cord (UCMSCs), and the placenta, in order to better understand their potential as a treatment option for MS.
An analysis of these clinical trials led the authors of this review to the consensus that MSCs appear effective in inhibiting CD4+ and CD8+ T cell activation, T regulatory cells, and macrophage switch into the auto-immune phenotype.
Further analysis of the specific MSCs used to treat MS by Alanazi et al. indicates that while BM-MSCs, AD-MSCs, and UCMSCs all demonstrate beneficial effects when applied to the treatment of MS, UCMSCs appear to be the best option.
According to the authors, UCMSCs demonstrate faster self-renewal than other MSCs, are able to differentiate into three germ layers, and can accumulate in damaged tissue or inflamed areas. Additionally, UCMSCs are also among the easiest MSCs to source, demonstrate a high concentration of MSCs, are safe and inexpensive, and are not associated with ethical issues.
Based on the information reviewed, Alanazi et al. recommend emphasizing the clinical utility of UCMSCs for regenerative medicine and immunotherapy, including for the treatment of MS.
Source: “Mesenchymal stem cell therapy: A review of clinical trials for multiple ….” 23 Aug. 2022, https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9420954/.
What is Crohn’s Disease?
Crohn’s disease is a chronic inflammatory bowel disease (IBD) that primarily affects the gastrointestinal (GI) tract. It is characterized by inflammation, which can occur anywhere along the digestive tract from the mouth to the anus, although it most commonly affects the small intestine and the beginning of the large intestine (colon). Crohn’s disease is a lifelong condition that can cause a variety of symptoms and complications.
Some of the common symptoms of Crohn’s disease include:
- Abdominal pain and cramping: This can range from mild to severe and is often located in the lower right abdomen.
- Diarrhea: Chronic and sometimes bloody diarrhea is a common symptom.
- Fatigue: Inflammation and other factors can lead to fatigue and a general sense of low energy.
- Weight loss: Reduced appetite and malabsorption of nutrients can result in weight loss.
- Loss of appetite: Inflammation can lead to decreased appetite and difficulties in maintaining a healthy diet.
- Fever: Inflammation and infection can cause fever, especially during flare-ups.
- Joint pain: Inflammatory processes can affect the joints, leading to pain and stiffness.
- Skin and eye problems: Some individuals with Crohn’s disease might experience skin rashes and eye inflammation.
The exact cause of Crohn’s disease is not fully understood, but it is believed to result from a combination of genetic, environmental, and immune system factors. The immune system in individuals with Crohn’s disease mistakenly attacks the healthy tissues of the digestive tract, leading to inflammation and the symptoms associated with the condition.
Crohn’s disease is a chronic condition with periods of flare-ups (active disease) and periods of remission (minimal to no symptoms). Treatment aims to manage symptoms, reduce inflammation, and improve quality of life. Treatment approaches might include medications to control inflammation, suppress the immune response, and alleviate symptoms.
In severe cases, surgery might be necessary to remove damaged portions of the intestine or address complications such as strictures (narrowing) or fistulas (abnormal connections between organs).
It’s important for individuals with Crohn’s disease to work closely with healthcare professionals, including gastroenterologists, to develop a personalized treatment plan and to manage the condition effectively.
What Testing is Done for Diagnosing Crohn’s Disease?
Diagnosing Crohn’s disease typically involves a combination of medical history assessment, physical examination, laboratory tests, and imaging studies. During the medical history assessment, a healthcare provider will inquire about the individual’s symptoms, their duration, and any family history of inflammatory bowel disease (IBD).
A physical examination might reveal signs of abdominal tenderness, swelling, or other indicators of inflammation. Laboratory tests such as blood tests can be conducted to assess for markers of inflammation, anemia, and nutritional deficiencies.
Additionally, stool samples may be analyzed to rule out infections and assess for the presence of blood or inflammation. To visualize the gastrointestinal tract, imaging studies like endoscopy and imaging techniques such as colonoscopy, upper endoscopy, capsule endoscopy, and imaging scans (such as CT scans and MRIs) are used.
These tests can help identify inflammation, ulcers, strictures, and other abnormalities characteristic of Crohn’s disease. Biopsy samples collected during endoscopy can provide further insight into the nature and extent of the inflammation.
The diagnosis of Crohn’s disease requires the integration of all these findings, as well as the exclusion of other conditions with similar symptoms, to arrive at an accurate and comprehensive diagnosis.
How is Crohn’s Disease Managed?
Crohn’s disease is managed through a combination of medical treatments, lifestyle modifications, and ongoing monitoring. The primary goal of management is to achieve and maintain remission (periods of minimal to no symptoms) while improving the individual’s quality of life.
Medical interventions often include medications that target inflammation, suppress the immune response, and alleviate symptoms such as abdominal pain, diarrhea, and fatigue. These can include anti-inflammatory drugs, immunomodulators, biologics, and, more recently, Janus kinase (JAK) inhibitors.
Nutritional therapy might involve dietary adjustments, potentially eliminating trigger foods, and ensuring proper nutrient intake.
Lifestyle modifications, such as stress management techniques, regular exercise, and adequate hydration, can also play a crucial role in symptom control.
For severe cases or complications like strictures and fistulas, surgical intervention might be necessary to remove damaged sections of the intestine or address complications.
Regular follow-up with healthcare providers is important to monitor disease activity, adjust treatment plans, and manage potential side effects of medications. Crohn’s disease management is individualized, with treatment plans tailored to each person’s specific needs and response to therapies.
An integrated approach involving gastroenterologists, dietitians, mental health professionals, and support groups helps individuals navigate their condition effectively and maintain a good quality of life.
Can Regenerative Medicine Help Crohn’s Disease?
Regenerative medicine, also known as stem cell therapy, is an emerging field that focuses on harnessing the body’s own regenerative capabilities to treat and repair damaged tissues or organs. Stem cells have the potential to differentiate into various cell types and promote tissue repair.
Mesenchymal stem cells (MSCs) are a type of adult stem cell that has gained attention for their potential therapeutic applications, including in the treatment of inflammatory and autoimmune conditions like Crohn’s disease. MSCs have the ability to modulate the immune response, reduce inflammation, and promote tissue repair, making them a promising candidate for regenerative medicine approaches. Potential mechanisms by which MSCs may benefit Crohn’s disease include:
Immunomodulation: MSCs have the ability to regulate immune responses, suppressing harmful inflammatory processes and promoting immune tolerance. This can help reduce the excessive immune response seen in Crohn’s disease.
Anti-Inflammatory Effects: MSCs secrete molecules that can dampen local inflammation and help create a more favorable environment for tissue healing.
Tissue Repair: MSCs have the potential to differentiate into various cell types, including those involved in tissue repair, thereby aiding in the regeneration of damaged intestinal tissue.
If you’re interested in MSC therapy for Crohn’s disease, discuss your options with a regenerative medicine specialist or healthcare provider who is knowledgeable to see if stem cell therapy is an opportunity for you to explore.
Investigating the Safety of Human Wharton’s Jelly Mesenchymal Stem Cell Therapy across Multiple Indications
Human umbilical cord Wharton’s Jelly derived mesenchymal stem cells (WJ-MSCs) are reported as the most potent cell source of MSCs, however, they remain understudied in comparison to other autologous sources of MSCs.
Mehling et al.’s study aimed to evaluate the safety of WJ-MSC therapy for a range of conditions and administration routines, including intravenous, intrathecal, and intra-articular delivery.
Wharton’s jelly (WJ) is the mucoid connective tissue that surrounds the vessels in the human umbilical cord and provides protection from compression and torsion in response to fetal movement.
According to this study, the use of WJ-MSCs has many advantages over autologous MSCs, including circumventing the pain and healing process of invasive stem cell harvesting from a patient. Additionally, WJ-MSCs offer the highest level of potency for therapeutic benefit and exhibit increased proliferation ability and anti-inflammatory effects.
Additionally, WJ-MSCs have been demonstrated to be safe and effective for many conditions. WJ-MSCs also do not cause or contribute to infusion-related toxicity, treatment-related adverse events, or ectopic tissue formation, even when administered at high dosages.
In this study, Mehling et al. confirm the safety of human allogeneic WJ-MSCs delivered at high doses and through multiple delivery routes (including intravenous (IV), intrathecal (IT), and Intraarticular (IA)).
Specifically, as part of this study, 22 subjects were evaluated for adverse events (AEs) for a period of 6 months following treatments with WJ-MSCs for a range of conditions, including neurological and osteoarthritic indications.
At the conclusion of the 6-month period of evaluation, the study reported an AE rate of 9.3% (3 subjects from the 32 doses administered in this study). The reported AEs consisted of chills and headaches, both transient and mild, and resolving without concern. While both of these AEs (headache and chills) are relatively common reactions to cell administration, 1 of the 3 AEs was deemed related to the administration procedure.
Additionally, blood profiling of 75 markers for health and disease in the subjects of this study demonstrated that WJ-MSC treatment poses no hematological safety concerns.
Considering the minimal occurrences of AEs observed following WJ-MSC therapy administered during this study, the authors support the use of WJ-MSC therapy for various indications in future clinical studies.
Source: “Safety study of cultured human Wharton’s Jelly mesenchymal stem ….” https://www.cellr4.org/wp-content/uploads/sites/2/2022/10/e3332.pdf.
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