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.
Because of its ability to simultaneously activate multiple mechanisms, including paracrine, trophic, immunomodulatory, and differentiation, researchers consider mesenchymal stem cells to be an effective option for stem cell therapy.
After years of active research, bone marrow-derived MSCs (BM-MSCs) have been a prevalent source for MSC-based studies. There is also active research using MSCs from a variety of other sources, including adipose tissue, peripheral and umbilical cord blood, amniotic fluid, skin, dental pulp, synovium, umbilical cord tissue, placental complex, and endometrium.
As part of this review, Arutyunyan et al. review umbilical cord-derived MSCs (UC-MSCs) as a prospective source for MSC-based therapy. More specifically, the authors focus on the potential therapeutic benefits of Wharton’s jelly, the gelatinous substance found in the umbilical cord stroma; of particular interest to researchers is the presence of mesenchymal-derived cells, including stem cells, with the absence of capillaries.
When studied in vitro, researchers found UC-MSCs demonstrated the ability to differentiate into a wide range of cells, including chondrocytes, adipocytes, osteoblasts, odontoblast-like cells, dermal fibroblasts, smooth muscle cells, and somatostatin-producing cells, sweat gland cells, endothelial cells, neuroglia cells, and dopaminergic neurons.
While it’s well known that MSCs produce a variety of bioactive compounds that supply a paracrine mechanism for their therapeutic activity, researchers have learned that UC-MSCs secretomes differ significantly from MSCs from bone marrow and adipose. Specifically, the most significant difference is UC-MSCs’ nearly complete absence of synthesis of the main proangiogenic factor, VEGF-A. UC-MSCs also demonstrate increased production of antiangiogenic factors when compared to BM-MSCs and AT-MSCs.
UC-MSCs have recently demonstrated the ability to transfer their own mitochondria into mitochondrial DNA-depleted cells. This observation has broad implications for the therapeutic potential of UC-MSCs, primarily due to the failure of mitochondria as an initial event in many diseases. In this regard, the authors conclude that the transfer of mitochondria provides a rationale for the therapeutic use of UC-MSCs for ischemic injury or disease linked to mitochondrial dysfunction.
Arutyunyan et al. found recent animal model preclinical studies regarding the use of UC-MSCs for the treatment of different diseases demonstrated promising results. Additionally, clinical studies involving UC-MSCs demonstrated to be safe with no significant side effects other than fever.
While the authors point out concern with the lack of standardized protocols for the isolation and expansion of UC-MSCs and of uniform requirements for the final product. Despite these concerns, the authors also conclude that the results of clinical trials using UC-MSCs are encouraging, particularly for the treatment of autoimmune and endocrine diseases.
According to the CDC, an estimated 3.1 million adults (1.3%) in the United States have been diagnosed with inflammatory bowel disease (IBD), which includes Crohn’s disease (CD) and ulcerative colitis.
Characterized by abdominal pain, severe diarrhea, fatigue, weight loss, and malnutrition, CD is thought to be the result of swelling and inflammation of the tissue of the digestive tract.
To date, there is not a clearly prescribed method for the treatment or prevention of CD. However, recently, researchers have found stem cells to be a promising treatment option, primarily for the observed ability to regulate immunity, repair injury, and control inflammation.
Building on the positive findings of previous studies that have used autologous stem cells or adipose-derived stem cells to treat CD and its associated complications, Zhang et al.’s randomized controlled clinical trial examines the use of umbilical cord mesenchymal stem cells (UC-MSCs) as a treatment for CD.
This study followed 82 patients who had been diagnosed with CD and had received steroid maintenance therapy for more than 6 months. Half of the participants were randomly assigned to receive a series of four peripheral intravenous infusions of UC-MCSs/kg administered over the course of a four-week period. Then, by using the Crohn’s disease activity index (CDAI) Harvey-Bradshaw Index (HBI), and corticosteroid dosage, participants in both the control and experimental group were followed up with over a 12-month period.
At the conclusion of this study, Zhang et al. found that the group receiving umbilical cord mesenchymal stem cells infusion experienced a significant decrease in the required dosage of corticosteroid dosage and a significant improvement in the overall condition of the patients. These findings led the authors to conclude that UC-MSCs can attenuate immune malfunction in patients with CD. Considering these findings, the authors suggest that the mechanisms of UC-MSC efficacy in CD be elucidated to better understand the precise selection of patients who receive this specific stem-cell treatment in the future.
The authors point out that, while the specific mechanisms of alleviating CD by UC-MSCs remain obscure, it is suggested that the downregulation of proinflammatory cytokines serves a beneficial role in the process.
The authors also raise concerns over the safety of the clinical application of stem cells in this application, highlighting conflicting findings as to the safety of the process. Considering the prevalence of stem cells’ ability to regulate and suppress immunity in other studies, Zhang et al. infer that the patient infections observed during their trial were associated with immunosuppression by stem cells.
While the study suggested that the peripheral infusion of UC-MSCs was convenient and safe, the authors point out that there was little distribution of UC-MSCs in the intestinal tissue and risk of cells being retained in the pulmonary capillaries. As a result, the authors call for future studies comparing the efficacy of interventional infusion into the inferior mesenteric artery to that of peripheral infusion. To know more about mesenchymal stem cell treatment for Crohn’s disease visit Stemedix website and read more related article.
Researchers continue to tout the potential of mesenchymal stem cells (MSCs) as an evolving approach for the repair of damaged tissue or lost cells.
Specifically, the ability of MSCs to differentiate and secrete beneficial factors and vesicles is believed to play the most influential role in the regeneration of injured tissues and cells affected by various diseases.
Recently, research into the regenerative potential of MSCs has focused on the extracellular vesicles (EVs) secreted by MSCs as an emerging and potential non-cellular therapeutic approach for healing or repairing injured or damaged tissue.
MSC-derived EVs (MSC-EVs), or cell-free therapies, in contrast to treatments based on whole cells, are easier to manage and safer due to lower amounts of membrane-bound proteins such as MHC molecules and their inability to directly form tumors.
In this review, Keshtkar et al. discuss and describe the extracellular vesicles released by MSCs and their therapeutic potential for addressing different disease models.
These EVs are membrane-packed vesicles that are secreted by a variety of cell types and found in a variety of physiological fluids. In addition to MSCs, EVs are also secreted by T cells, B cells, dendritic cells, platelets, mast cells, epithelial cells, endothelial cells, neuronal cells, cancerous cells, and embryonic cells. EVs are also found in urine, blood, breast milk, saliva, cerebrospinal fluid, synovial fluid, and amniotic fluid.
EVs have repeatedly demonstrated that they perform an important role in cell-to-cell communication and have been implicated in a number of important processes, including the immune response, homeostasis maintenance, coagulation, and inflammation.
Several studies have explored the use of MSC- EVs as therapeutic treatment options for kidney disease, liver disease, cardiovascular disease, and neurological disease. The authors of this review report the beneficial therapeutic effects of MSC-EVs in each of the disease models listed above, which include a significant reduction in inflammation, improved angiogenesis, reduced oxidative stress, the suppression of fibrosis, and increased cell proliferation.
Keshtkar et al. conclude that EVs can be easily isolated from MSCs of various origins and can be transferred to target cells to introduce therapeutic effects that include the regeneration of tissue and suppression of inflammation. Additionally, the authors point out that EVs could be an effective, safe therapeutic option.
Considering the potential therapeutic benefits of MSC-EV regenerative therapy, the authors suggest standardizing methods for EV isolation, characterization, and administration as ways to provide safe, effective, and powerful new therapies based on MSC-EVs.
Osteoarthritis (OA) is the most common and widespread form of arthritis, affecting an estimated 655 million people worldwide. Occurring as a result of cartilage degeneration, OA is a progressive degenerative disorder that most commonly affects the joints of the hands, hips, knees, and spine.
Although OA can affect anyone, it is most commonly observed in older patients. In fact, all individuals over the age of 65 are believed to demonstrate some clinical or radiographic evidence of OA.
While surgical and pharmaceutical treatment options for OA exist as a way to manage the symptoms and progression of the disease, treatment for the restoration of normal cartilage function has yet to be achieved.
Considering the tissue of joint cartilage is composed primarily of chondrocytes found in bone marrow-derived mesenchymal stem cells (BMSCs), using these specific stem cells appears to have significant potential for use in the therapeutic regeneration of cartilage.
In this review, Gupta et al. evaluate the advances in using BMSCs and their therapeutic potential for repairing cartilage damage in OA. Evaluating current research, the authors point out that one of the key characteristics of MSCs, including BMSCs, is that they are generally hypoimmunogenic and possess immunosuppressive activity, suggesting that BMSCs could be used as allogeneic applications for cartilage repair.
Preclinical models of OA have also demonstrated that the effects of MSC transplantation have been effective for cartilage repair. Additionally, clinical models have reported on the safety and positive therapeutic effects of MNSC administration in patients with OA.
The authors point out that while the exact mechanism by which BMSCs regenerate articular cartilage in patients with OA is not clear, their ability to induce proliferation and tissue-specific differentiation appears to aid in the repair of damaged cartilage.
The ability of BMSCs to migrate and engraft onto multiple musculoskeletal tissues and differentiate at the site of injury while demonstrating anti-inflammatory and immunosuppressive properties demonstrate their potential as a therapeutic treatment for degenerative diseases like OA.
While the information provided in this review demonstrates the potential of BMSCs to support treatment and recovery from the damage caused because of OA, Gupta et al. call for additional clinical studies to assess the curative properties and long-term outcome of using MCSCs for the treatment of OA before they can be used routinely as a clinical treatment for the condition.
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