Safety of Stem Cell Therapy

In the modern world, the issues concerning the safety of stem cell therapy have been incredibly relevant. Many people ask themselves, are stem cells safe, without a conclusive answer. However, before a definite answer can be given on whether cell therapy is safe, one has to understand what said safety implies.

When it comes to cell therapy, the risk of cancer is one of the most common safety concerns among patients and doctors alike. In order to have deeper insight, it is necessary to dismiss all speculations from individual journalists, medical officers, and patients. Instead, one should focus on authoritative scientific evidence. 

Before we start analyzing the scientific facts, let’s define the term “cell therapy”. It involves a variety of cellular products in their pure form, as well as tissue-engineered structures and surgical techniques, used to promote regeneration thanks to the ability of body cells.

For those asking are stem cells safe, this article will answer that. It will also discuss their origin and the safety and side effects of stem cell therapy.

What are stem cells?

Stem cells are the body’s foundational cells that give rise to all other cells. This ability allows stem cells to be used to repair parts of the body that would otherwise be irreparable.

For instance, let’s look at what are known as multipotent mesenchymal stromal cells (MSCs, or MMSCs). These are a type of adult stem cells capable of differentiation in various directions. This includes adipo-, osteo-, chondro-, neuro-, myogenic, and others. That is fat, bone, cartilage, nerve, and tissue cells, respectively. This demonstrates the potential that stem cells have to treat so many kinds of diseases.

Where do stem cells come from?

The most frequently used type of cells in cell therapy are the multipotent mesenchymal stromal cells (MMSCs). These cells are present in every organ and tissue where they regulate the regeneration process. MMSCs can be easily isolated from various available sources in the human body. These include bone marrow, adipose tissue, oral mucosa, umbilical cord, heart, muscles, and others.

The patient’s own tissues, such as bone marrow and adipose tissue, are predominantly used to get MMSCs since they contain the highest concentration of the desired cells. In cases where these are used to treat the same patient, these cell-based products are called ‘autologous’ stem cells.

In cases when it is impossible to obtain the patient’s own biomaterial (contraindications to sampling, an insufficient amount of cells in the patient’s biomaterial, or lack of time to prepare the cell-based product in event of acute conditions), donor tissue-derived cell products can be used. Such cell-based products are called allogeneic. Donated stem cells are taken from umbilical cord blood, Wharton’s jelly and placenta, received after a healthy birth.

It was found that the properties of stem cells harvested from different tissues are virtually identical regardless of the source. However, the main and most studied MMSCs sources in an adult are bone marrow, adipose tissue, umbilical cord, and placenta.

Stem cells can also be derived from non-adult tissues. They can be taken from fetal tissue (fetal stem cells), as well as embryonic tissue (embryonic stem cells). However, the latter is associated with ethical concerns. Some may ask, is stem cell therapy effective with MMSCs over embryonic cells? It is, which means there’s no need to cross that ethical divide.

How do stem cells work for therapy?

The therapeutic effect of MMSCs is found in paracrine regulation and direct influence on the surrounding cells. MMSCs secrete a significant amount of cytokines, chemokines, and adhesion molecules. These regulate various molecular signalling pathways by activating and/or blocking them. Due to paracrine signals, in particular, MMSCs potentiate the survival and proliferation of endogenous cells. They also inhibit apoptosis and activate the differentiation of resident progenitor cells. This ultimately leads to the improved function of the damaged tissue.

It was established that MMSCs are capable of influencing inflammatory processes and stimulating angiogenesis. A large number of cytokines, produced by MMSCs, block the inflammation signals that occur during various conditions, including autoimmune processes.

All these properties of stem cells are successfully used to treat a number of health conditions, including neurodegenerative diseases, lung and heart diseases, disorders of the digestive system, injuries of the musculoskeletal system, etc.

Is stem cell therapy safe?

Popular questions asked about therapy based on stem cells include are stem cells safe, and are stem cell treatments safe. Peer-reviewed publications provide evidence that cultured MSCs are vulnerable to malignant transformation and can trigger tumorigenesis. However, if you look deeper into all the provided experiments, you will notice something peculiar. These experiments were conducted either on animal cells (mice, rats) or human cells that were genetically modified using growth-promoting substances.

The case is that the process of obtaining a therapeutic dose of a cellular product takes a long time. This period, undoubtedly, depends on the individual specific features of the patient’s organism. For example, their past medical history, bad health habits, and various other factors. It typically requires at least 3 weeks. 

That is why many researchers and formulators try to reduce the length of the period needed to obtain the therapeutic dose of MMSCs. This is achieved by using numerous proliferation stimulants that accelerate cell division but at the same time may lead to changes in the cell’s properties, including the capacity for malignant transformation. A while back, an established journal published several articles, where numerous researchers reported the occurrence of spontaneous oncotransformation during long-term cultivation of the MMSCs. However, these articles were removed later and explanatory notes were added, stating that the researchers had accidentally cross-contaminated the MMSCs cultures with tumor cell lines.

So, is stem cell therapy safe? There is no scientific evidence of mesenchymal stem cells’ capability of spontaneous transformation when using a culture medium and serums specifically designed for MMSCs (unlike fetal or embryonic cells, which may show abnormal growth). With proper quality control, there’s no reason to be convinced that the therapeutic use of stem cells can cause such.

More importantly, the safety of MMSCs is further reflected in the total number of clinical safety studies. After all, the main goal of any clinical trial, especially if it is conducted for cell-based products, is their safety assessment. These trials ask, among other things, is stem cell research safe. According to ClinicalTrials.gov, there are 9144 studies registered as of June 2022, of which 3745 have been already completed. These trials were carried out for autoimmune diseases, skin diseases, neurological conditions, etc., among patients of different nationalities, age groups and gender. The geographical spread of said clinical studies is available in the figure above.

Can the body reject stem cells?

In the past, MMSCs were considered to be entirely immune-privileged cells. This means they do not carry histocompatibility complex class I molecules on their surface. However, over time, they have been branded more as immune evasive. This refers to them having very low immunogenicity. This is a result of certain new studies describing antibodies to these stem cells. 

So, with this known, is stem cell safe to use for therapy even with the risk of minimal rejection? Despite this, there is yet to be any proven difference in their efficacy, even when antibodies are formed. While it is possible for stem cells to be rejected in rare instances, there is no proof that rejection affects their effect. Human embryonic stem cells are also shown to be unable to induce an immune response. Also, mesenchymal stem cells are used to regulate anti-donor immune responses in transplant recipients.

Essentially, stem cells can be considered mostly unrecognizable to the immune system. 

What are the negative effects of stem cell therapy?

Just like any medical procedure, cell-based treatment is not without potential negatives. Those asking is stem cell therapy effective, will be pleased to know it is. However, it is important to be aware of the downsides of treatment before embarking on them.

Firstly, it is important to choose a stem cell clinic after due diligence. It should be kept in mind that stem cells are not a panacea. All patients are different, and while this kind of treatment may be very effective for one person, it may have very little effect on another.

• Stem cell therapy tends to be expensive. This is not surprising as it leverages cutting-edge science for treatment purposes. In many cases, it provides an option for treatment for conditions that are considered to have no cure. For instance, it can be used in autism, multiple sclerosis, or spinal cord injury.
• Infections at the site of stem cell administration. This is a rare effect to see arise, however, it does, in very scarce instances. Despite this, to those asking is stem cell injection safe, the risks are minimal. When conducted by a professional team, this is unlikely to be seen.
• Since the popularization of stem cell therapy, there have been concerns regarding its ethics. The reason for this was that most people believed that cell-based treatment made use exclusively of embryonic stem cells from aborted babies. However, in the modern-day, reputable centers opt for MMSCs from adult tissues — own patients or donated stem cells from umbilical cords and placenta.

Possible adverse reactions of stem cell treatment

The commonest of these adverse reactions and the factors that may affect their occurrence and intensity are listed in the table below.

In most cases, we do observe no adverse effects that can be had in patients receiving drugs based on mesenchymal stem cells at the Clinic. Short-term fever (less than 5% of treatments) is the most common one.

Advice for people considering stem cell therapy

For those considering medical procedures based on the introduction of stem cells, it is important to understand their potential and possible outcomes. Many query it by asking, is stem cell therapy effective? This kind of treatment can greatly improve symptoms of conditions that are otherwise very hard to treat. However, those considering it should know that stem cells may not produce the same effect in all patients. Some patients will notice very little improvement if any, and some will improve a lot. All patients and their conditions are different, and stem cell therapy effectiveness will also be. The fact is that this method provides a safe, ‘natural’ way to treat conditions while having almost no side effects.

If one makes the decision to go for stem cell therapy, one should make sure to select a reputable center. Sometimes people ask are stem cell treatments safe, mentioning adverse reactions that they may have heard anecdotally. However, many side effects can be avoided when treated by well-trained healthcare professionals. These centers are also more likely to combine other therapies for the greatest effect.