Decades ago, discovery of stem cells brought hope with its regeneration potential. Scientists dived into stem cell research to design therapies for different disorders. With the revealed potential of mesenchymal stem cells (MSCs), a new avenue opened up to find different sources of stem cells. The human umbilical cord became the preferred option for MSC extraction for its numerous advantages. Though their use in therapy is under investigation, this article describes the advantages, benefits, and applications of human umbilical cord-derived mesenchymal stem cells (hUC-MSCs).
Human Umbilical Cord Mesenchymal Stem Cells
Mesenchymal stem cells (MSCs) are mesodermal in origin exhibiting multipotency. Although bone marrow was their initial source of extraction, with time, other sources have surfaced, including dental pulp, adipose tissue, and umbilical cord. The following are the advantages of utilizing umbilical cord MSCs in therapy:
Potency: The potency of stem cells decreases with age, thereby limiting the therapeutic potential of stem cells derived from adult tissues. hUC-MSCs do not incorporate age-induced effects, thus retaining their potency. Many studies have confirmed their higher regeneration potential. Their expression profile is similar to that of embryonic stem cells, which are banned due to ethical implications. Therefore, their potential lies between embryonic and adult tissue stem cells.
Immunogenicity: The cord MSCs also show low amounts of HLA markers, responsible for graft-vs-host disease and immune rejection. Therefore, the incidence of adverse reactions is substantially lower with them rather than with bone marrow MSCs.
Extraction: The collection procedure is easy and non-invasive. The cord is considered to be a waste which is discarded after birth. Therefore, the collection is ethically acceptable and yields large numbers of cells.
These advantages have given hUC-MSCs an upper hand for autologous and allogeneic stem cell therapy.
Biological Characteristics
The human umbilical cord contains MSCs in three regions: inside the endothelium, in the perivascular region, and the Wharton jelly. Wharton jelly is a sponge-like tissue enriched with MSCs. Scientists have verified that the potential of MSCs is similar in different cord regions. The extraction of hUC-MSCs from cord blood or Wharton’s jelly is frequently performed. The extraction procedure from Wharton’s jelly uses an explant or enzymatic digestion method. Their therapeutic potential not only arises from their regenerative ability but also from the following biological characteristics. This article refers to the hUC-MSCs as those prepared from Wharton’s jelly.
Immune Modulation: They inhibit the adaptive immune system and polarize macrophages towards repairing the M2 phenotype. They also increase the levels of regulatory T cells (Treg) that regulate autoimmune response.
Paracrine Effects: These cells secrete numerous soluble growth factors including hepatocyte growth factor (HGF), keratinocyte growth factor (KGF), epidermal growth factor (EGF), etc. These factors induce tissue regeneration.
Anti-inflammation: They also secrete anti-inflammatory mediators such as IL4, IL10, TGFβ1, etc., while suppressing pro-inflammatory cytokine secretion.
Antioxidant: They also relieve oxidative stress from cells, thereby reducing their apoptosis.
Anti-fibrotic: Fibrosis is a chief molecular event in numerous disorders. hUC-MSCs diminish fibrosis by promoting the apoptosis of fibrosis-causing cells and regulating the underlying signaling pathways.
Immunosuppressive Properties
The modulation or suppression of the immune system has facilitated the use of hUC-MSCs. They express very low amounts of HLA molecules and also lack the expression of CD80 and CD86, which cause T-cell activation. Therefore, the possibility of their immune rejection after an allogeneic transplant is low. Additionally, these cells also release factors like prostaglandin E2 (PGE-2), HLA-G5, indoleamine 2,3-dioxygenase (IDO), etc., that suppress the proliferation of immune cells. Research has suggested that priming of hUC-MSCs with activated immune cells or mediators turns these cells into immunosuppressors. They also inhibit the differentiation and maturation of dendritic cells. Furthermore, they also release activin-A and HLA-G6 to suppress INF-ϒ released by natural killer (NK) cells and their cytolytic activity. A study by Wu et al. indicated that hUC-MSCs improved stem cell engraftment while reducing GVHD.
Adverse Effects
More than 100 clinical trials are underway or finished employing hUC-MSCs. However, doubts regarding their safety crop up every once in a while. Hematopoietic stem cell transplant showed immune rejection and GVHD, whereas ESCs form tumors. It is only logical to consider them as potential risks with hUC-MSC transplantation. However, none of the studies in animals and humans alike have reported any adverse reactions, indicating that the cells are well-tolerated. Wang et al. have shown the absence of any tissue-based toxicity over a period of 6 years.
Clinical Applications
Several diseases, especially those lacking a proper cure, employ hUC-MSCs. These primarily include damaged tissues and degenerative disorders.
Diabetes: Diabetes is characterized by hyperglycemia and broadly categorized into type I and type II based on the underlying cause. The patients often develop insulin dependency resulting in complications in long term use. The hUC-MSC infusion showed differentiation into insulin-producing islet cells. Furthermore, clinical studies demonstrated improvements in insulin levels and normal glucose levels and reduced dependency on drugs.
Liver Damage: Liver damage usually involves the fibrosis stage, that is, excessive accumulation of extracellular matrix by hepatic stellate cells. The cord MSCs stimulate the apoptosis of these cells and the degradation of the matrix by expressing matrix metalloproteinases. They also alleviate neutrophil recruitment, liver cell apoptosis, inflammation, and oxidative stress, thus protecting against ischemia-reperfusion injury. By regulating the proliferation of stellate cells, they delay and can potentially reverse liver damage.
Arthritis: Arthritis is a degenerative disorder of joints triggered by many factors. The cord MSCs treat the condition by differentiating into osteoblasts and chondrocytes. They also promote the apoptosis of T cells and suppress inflammation that damages the tissue. Both the mechanisms delay the cartilage destruction, thus exhibiting a chondroprotective effect. They also promote chondrocyte proliferation and inhibit other immune cells like NK cells, dendritic cells, M1 macrophages, etc. Their administration into patients has resulted in better joint function and quality of life.
Stroke: Stroke occurs due to ruptured or blocked blood vessels in the brain which leads to low or negligible blood supply, resulting in death of brain cells. hUC-MSCs induce vessel formation and exhibit neuroprotective effects by releasing glial cell-derived growth factor and brain-derived neurotrophic factor.
Neurological Disorders: These disorders can be degenerative, injury-based, or developmental in nature. hUC-MSCs modulate immune response, exhibit neuroprotective effects, and reduce oxidative stress that decreases cell apoptosis. The positive outcomes have been the result of their ability to form nerve cells. Their administration showed inactive lesions in patients with multiple sclerosis.
In A Nutshell
The cord MSCs’ distinct biological characteristics boost their therapeutic effectiveness. Their usage over other MSC sources has become easier owing to their non-invasive, painless collection and greater capacity for regeneration. It has spurred the industry of cord blood banking and the utilization in clinical trials. None of the trials went to Phase III. However, Phase I/II studies have reported positive outcomes without any safety issues.
On the contrary, their immunosuppressive abilities have decreased the phenomenon of GVHD, according to research. Their clinical translation requires optimization of treatment protocols like dosage, administration route, etc. Additionally, phase III clinical trials can ultimately validate their efficacy and safety. Kosheeka provides MSCs from umbilical cord and other sources to enhance stem cell research. Our team characterizes the product thoroughly and runs high-throughput tests to assure the quality and purity of the product.
FAQs
Q: How are mesenchymal stem cells (MSCs) from the human umbilical cord better than those from other sources?
MSCs from the umbilical cord do not contain the age-induced changes that are present in those from adult tissues. Human umbilical cord MSCs (hUC-MSCs) have higher regeneration potential, and they can be noninvasively extracted in high quantities.
Q: What are the therapeutic properties of hUC-MSCs?
They show anti-inflammatory, immune-modulating, anti-fibrotic, and antioxidant properties, in addition to inducing repair by paracrine effects.
Q: How do hUC-MSCs suppress the immune system?
They release various factors that inhibit the proliferation of immune cells, thereby exhibiting immunosuppressive properties.
Q: Are hUC-MSCs safe for therapeutic applications?
Numerous clinical trials have shown that their application does not cause any adverse effects, deeming it safe.
