What are Umbilical Cord Mesenchymal Stem Cells?
Umbilical cord mesenchymal stem cells (UC-MSCs) are self-renewing and multipotent. They can continuously proliferate and differentiate under specific conditions into one or more cell types that constitute human tissues and organs.
They affect immune responses and can be easily harvested, separated, cultured, expanded and purified.
Currently they are being used in the treatment of various diseases. They have several distinct properties essential for their therapeutic applications. These properties are:
- Differentiation. The generation of differentiated cells by UC-MSCs promotes tissue regeneration and improves tissue function.
- Immune regulation. They can inhibit the proliferation of immune cells, such as T cells, B cells and induce the differentiation of macrophages from pro-inflammatory phenotypes to anti-inflammatory phenotypes, reducing inflammation by secreting interleukin-10 (IL-10) and interleukin-4 (IL-4). Both modifications facilitate tissue repair.
- Paracrine effects. UC-MSCs promote tissue regeneration by secreting soluble molecules, such as hepatocyte growth factor (HGF), epidermal growth factor (EGF). and other cytokines.
- Antiinflammatory effects. UC-MSCs suppress the secretion of inflammatory factor interleukin-1β (IL-1β), tumor necrosis factor-α (TNF-α), and interleukin-8 (IL-8), reducing inflammation and oxidative stress, thus suppressing cell apoptosis.
- Non-coding RNA regulation. They can affect the expression of microRNA (miRNA), long non-coding and circular RNA, indirectly regulating their target genes and achieving therapeutic effects.
Application of UC-MSCs in Clinical Treatments
Diabetes is a metabolic disease characterized by hyperglycemia resulting from insufficient insulin secretion, impaired response to insulin or both. Clinically there are 2 main types of diabetes: type 1 insulin-dependent diabetes mellitus (T1DM) and type 2 insulin-independent diabetes mellitus (T2DM).
It has been shown that UC-MSCs injected intravenously in diabetic animals can home to pancreatic islets and differentiate into functional islet-like cells. In diabetic patients, 6 months to 1 year after intravenous injection of HUC-MSCs, the metabolic index was improved, the level of insulin and C-peptide was increased, the number of Treg cells was elevated, while glycosylated hemoglobin, fasting glucose, and daily insulin requirement were decreased.
UC-MSCs have shown to be effective and safe in the treatment of diabetes.
UC-MSCs have been applied for diabetic foot, diabetic nephropathy and diabetic wound ulcers. In the clinical treatment of diabetic food, MSCs can increase the formation of vascular endothelial growth factor (VEGF), which could promote the epithelialization of ulcerated tissue by stimulating extracellular matrix formation.
In a clinical study, 5 patients aged 30–60 years, with chronic diabetic non-healing wounds, received UC-MSC transplantation and were followed up for 1 month. The healing time and the size of the wound significantly shorten after UC-MSC treatment.
Treated patients exhibit significant improvement in ankle-brachial pressure index, oxygen tension and claudication distance. Moreover, the density of newly formed vessels increased, and ulcers healed partially or completely.
When applied in the treatment of diabetic nephropathy, they exerted a therapeutic effect by reducing the expression of inflammatory cytokines, increasing the number of Sertoli cells, and upregulating the expression of their proteins and enhancing expression of anti-apoptotic proteins in the kidney.
Hepatitis and cirrhosis are common liver diseases, and fibrosis is the common pathway underlying the development of multiple chronic conditions of the liver. The activation of hepatic stellate cells (HSCs) is a critical element of the cause of the fibrosis, which can be inhibited by UC-MSCs.
UC-MSCs inhibit proliferation and promote apoptosis of HSCs, delaying or even reversing liver fibrosis and fibrosis-related liver diseases. They can also release exosomes that can reduce the expression of NLRP3 inflammasomes and decrease the level of pro-inflammatory factors, thereby achieving an anti-inflammatory effect; and UC-MSCs can reduce the level of ALT and AST, suppress the infiltration by neutrophils, decline oxidative stress and apoptosis of liver cells.
Systemic Lupus Erythematosus
Systemic lupus erythematosus (SLE) is an autoimmune inflammatory disease of the connective tissue involving multiple organs. SLE affects prevalently young women. In most patients, traditional therapies can manage the condition but are associated with a high rate of adverse reactions that can affect the patient’s quality of life.
The immunoregulatory functions of UC-MSCs have been widely employed for the treatment of various autoimmune conditions and beneficial effects have been obtained. The treatment has shown to be safe and effective.
UC-MSCs can play a role in the treatment of SLE by inhibiting the proliferation of T cells, increasing the number of Treg cells, inhibiting the expansion of Tfh cells, maintaining the balance between T helper 1 and T helper 2 cells (Th1/Th2), and decreasing the level of TNF-α and IL-17.
Arthritis is an inflammatory disease that affects joints and surrounding tissues. Its etiology is complex and mainly related to an autoimmune reaction. Traditional treatments do not effectively solve the problem of the lack of immune tolerance mechanisms and are burdened by obvious side effects.
UC-MSCs have been show to effectively treat arthritis by differentiating into osteoblasts, inhibiting the proliferation and promotion of apoptosis in T lymphocytes, reducing secretion of pro-inflammatory cytokines, such as IL-1, IL-6, IL-7 and TNF-α.
After treatment, joint function and quality of life is significantly improved. UC-MSCs also have chondroprotective effects, which is considered to depend on the reduction of inflammation, which delays cartilage destruction. They can also differentiate into chondrocytes.
Brain Injury and Cerebrovascular Disease
The incidence of death and disability in these conditions is high. Traditional therapies do not provide satisfying results and the sequelae of the damage can be severe.
It has been shown that the motor and nerve function scores in patients treated by HUC-MSC transplantation were improved, implying that this therapeutic modality can significantly reverse brain function injury. Animal experiments demonstrated that HUC-MSC transplantation increased the release of VEGF, stimulated angiogenesis, and produced an anti-inflammatory effect by reducing the level of inflammatory factors.
Also, the use of exosomes derived from UC-MSCs has shown to increase myelin formation and decrease in glial hyperplasia.
Methods to deliver UC-MSCs for brain injury include lumbar puncture, venous infusion and direct injection into the brain.
Heart disease is the first cause of mortality worldwide, with approximately 20 million people dying from the disease every year.
Available treatments include heart transplantation, surgical interventions, and pharmaceutical therapies. Surgical treatment is typically associated with complications and generally is not recommended unless the condition is severe.
UC-MSCs have shown to treat and relieve various cardiovascular diseases, including myocardial infarction, heart failure, myocardial ischemia and myocarditis. These cells promote cardiac tissue regeneration and angiogenesis, inhibit inflammation, and significantly reduce infarct size and mortality.
These cells can have a therapeutic effect in heart diseases by: differentiate into cardiomyocytes to improve heart function; differentiate into vascular endothelial cells to promote angiogenesis; improve cardiac performance by inhibiting myocardial cell apoptosis; paracrine antiinflammatory effects and regulating expression of miRNAs.
Mesenchymal stem cells are an important research subject in the field of regenerative medicine. Multiple clinical trials have proved that they have a significant therapeutic effect in multiple conditions. These types of cells bring hope for the future of regenerative medicine due to their remarkable potential to differentiate, proliferate and their low immunogenicity.
At Zignagenix we offer the majority of the previously clinical applications of UC-MSCs and more. You can schedule a consultation with one of our team members to see if you are a candidate for our therapies and to see what we can do to improve your medical condition or to simply improve your overall health.
Click here to schedule your free consultation:
Xie Q, Liu R, Jiang J, et al. What is the impact of human umbilical cord mesenchymal stem cell transplantation on clinical treatment?. Stem Cell Res Ther. 2020;11(1):519. Published 2020 Dec 1. doi:10.1186/s13287-020-02011-z