Choosing wisely

Clinics around the world use the generic term ‘stem cells’ to denote therapies for complications supposedly unresolvable through conventional medicine. A growing number of people for whom conventional medicine hasn’t produced favorable outcomes, seek alternative routes toward healing. With the general association of reconstructive healing with ‘stem cells’, the term has gained significant marketing value for thousands of clinics now rendering biological material of all sorts under this single category.

What you need to know

‘Stem cells’ broadly categorize any cell capable of differentiating into another type of cell. This capability creates therapeutic advantages wherever regeneration of damaged tissue is practically possible. This possibility and its success or failure, largely depend on the type of damaged tissue, the type of cells administered, quantity, viability, and secondary constituents of the ‘cell-mix’ being administrated. In other words, a lot of ‘IFs.

What doesn’t work

Not knowing what is being injected and how your body will respond to the chosen administration is by far the most common cause of non-efficacy and adverse events.

Globally, a wide range of biological material is administered under the common tag word, ‘stem-cells’. Such clinics stick to general administration methods, often easily carried out by nurses and without considering how the chosen method will impact the biological product during the administration and after coming in contact with the recipient’s body environment. In conventional medicine, drugs are tested for toxicology and bioavailability before marketing approval is granted by health regulatory authorities. Such tests are not performed for experimental cell products as these clinics don’t operate under the same biopharmaceutical regulations. Therefore what the product transforms into or how your body can respond to it, remains largely unknown. Lately, a growing patient distrust toward conventional medicine is paving the way for clinics offering common intravenous, intranasal, or intrathecal administrations of abortion bio-waste thought to be rich in mesenchymal stromal cells. These sources are commonly referred to as ‘fetal’ or ‘placental’ derivatives. Common risks like donor blood contamination of these products during their processing are most often the culprit behind a prolonged immune reaction post-therapy. Clinics offering these therapies are funded by their governments to boost medical tourism and conveniently placed at tourist destinations where local health regulators turn a blind eye to foreigners receiving these ‘stem-cell’ therapies. Ironically the same health regulatory relaxation does not apply to the locals seeking human experimental products in these countries.

Purity

The US FDA categorizes cellular products under ‘biological drugs’ and renders a streamlined, needs-based (disease-centric) clinical development approach.

Cellular products in biopharmaceutical research require characterization techniques to define the baseline purity of the biological product before use. Endothelial, epithelial, and neural cell lines are therefore refined by their glycoprotein characteristics to ensure statistical accuracy, often supporting formulations under clinical trials worth millions of dollars in ongoing expenditure and subject to future regulatory disapproval risk. This massive financial risk governs the significance of cellular purity in biopharmacological applications. The same level of precision is not practiced by therapy providers treating foreigners on vacation, given the ‘needless’ laboratory compliance expenditure.

Therapeutic Application

‘Stem cells’ commonly used in experimental therapies are multipotent, that is; they can differentiate into specific types of tissue, not all types of tissue. This creates the essential need for a clinician to know the purpose and scope of multipotency of their cellular products and for what conditions they may not work or cause an adverse reaction. Most clinics providing these therapies are buying their cell products from central labs and, therefore have no understanding of what is being injected into a patient.

Multipotency limits the differentiation capability of cells. For example, allogeneic hematopoietic cells cannot form neurons and often cause immunogenic reactions, while mesenchymal cells can differentiate into oligodendrocytes to aid remyelination but also cannot become neurons. To administer a safe and effective therapeutic protocol, a clinician needs to have a precise understanding of the disease or disorder to be treated and choose the cell types and administration protocols accordingly.

A therapy that (1) addresses the disease pathology or all courses of the disorder, (2) with the most appropriate regenerative elements, (3) processed for each specific administration route environment, (4) administered in their optimal state of health, (5) in quantities adequate for each course of the condition, and (6) closest to all areas of damage, becomes a successful therapy.

The only way to make good use of cellular therapy is to not use it like a vitamin supplement, a pain killer, or an antibiotic. The actions of cellular therapy are either directly or indirectly limited to regeneration only. Provided the causes of degeneration are tackled separately first, regeneration can overcome damages rendered by a disease or disorder, thereby allowing the patient to overcome challenges in their recovery. With no therapeutic impact on the underlying causes, no regeneration can last.

Clinicians that fail to understand your condition, will fail to choose the right cell mix for you. Clinics rendering cheap, general administration methods are cell salesmen. Clinics rendering the same product for all conditions are no different. Apart from a failed therapy, many adverse immune responses can worsen the baseline condition.

Risk factors

Cryoprotectants like Dimethyl sulfoxide (DMSO), dead cell debris, immune cell contamination, blood contamination, and abortion waste (fetal, placental) are the most common sources of trouble.

Surprisingly, many of these elements are now being promoted as beneficial. For example, DMSO is cytotoxic and begins to kill the cells it preserves, the moment the cells are thawed. Lack of knowledge, washing infrastructure, or plain arrogance has led to the human administration of low-viability cells along with DMSO into numerous patients who have suffered months to years of immunogenic reactions post-therapy. DMSO is used to preserve the integrity of cryopreserved cells during storage and transport from central labs to the clinics rendering therapies.

To avoid the risks of DMSO, some clinics have resorted to transporting cells in dry ice without DMSO, which significantly impacts viability, leading to an even worse bioload of dead cell debris.

The viability of cryopreserved cells transported, thawed, and washed accurately will remain within the range of 40-80%, which implies that at least 20% dead cell debris gets administered to patients receiving these therapies. Dead, decomposing cell protein can not only stir up the immune system into hypercytokinemia but also result in infections commonly noted after bone joint ‘stem cell’ injections.

Anything that is blood-derived will need to be HLA (Human Leukocyte Antigens) matched between the donor and recipient. Allogeneic hematopoietic cell lines come under this category. Despite HLA matching, hematopoietic cells sometimes cause temporary immune reactions in recipients. While tissue-derived multipotent cells such as mesenchymal lines will not. Therefore any rookie donor blood contamination during the lab processing of source tissue before harvesting cells can lead to the donor’s hematopoietic or immune cells entering the culture, thereby posing a serious risk for human therapeutic use.

Fetal cells

A new name has surfaced in recent years, originating from countries that lack an adequate supply of healthy multipotent cell tissue sources. Instead of using healthy umbilical cord tissue to source mesenchymal cells, some clinics separate mononuclear fractions from abortion fetal remains. These are known as ‘fetal’ cells which is not a scientific term to denote any specific cell line. Not only can such extracts pose a massive health hazard from infections, but most constituents of these products lack any glycoprotein identification, thereby leaving the patient with permanent autoimmunity amongst other multi-organ complications.

Placenta

Another drill carried out by clinics involves the use of Human Placenta Acetone Powder supposedly containing beneficial ‘nutrition’ for the injected ‘stem cells’. It is to be noted that multipotent cells do not require any placental derivatives for survival or division in the recipient’s body. The Centers for Disease Control and Prevention has issued a warning against consuming placenta-based products due to proven infection risks. There is no clinical evidence that consuming placenta or implanting human placenta powder below the skin provides any health benefit or aids cellular paracrine activity. This is another health hazard considering the lack of regulatory enforcement during the processing and manufacturing of such products which require complex decellularization methods, bioavailability tests, and protein characterisation to ensure safe human administration.

Exosomes

Exosomes are vesicles; extracellular pipes to transmit proteins used to communicate with other cells. Clinics ‘selling’ exosomes fail to address what those ‘pipes’ contain at the time of harvest and paint an image of exosomes in the minds of patients that portrays them as supplements to aid cell-based regeneration. Such claims have no scientific basis given that exosomes are generated by specific cells to communicate or respond to specific paracrine signals, always dependent on what activity the cells or host tissue are engaged in at the time of harvest. In simple terms, clinics selling exosomes have no idea what those vesicles contain, which equals further risk of immune hazards for the patient already suffering from a condition.

Amniotic fluid

In the early weeks of pregnancy, amniotic fluid is comprised of water from the mother’s body. Beyond 20 weeks of pregnancy, the fetus’s urine makes up most of the fluid. Amniotic fluid is said to contain nutrition, hormones, antibodies, and natural killer (NK) cells amongst other bio-loads specific to genetics.

Though natural killer cells have been known to improve immunodeficient conditions, their role in regenerative healthcare is not relevant. Therefore the direct application of amniotic fluid along with the fetus’s urine to improve degenerative conditions is of very limited significance and poses huge immune risks. For immunotherapies, given the bio-load and complexity of separating NK cells from amniotic fluid, umbilical cord blood is a superior choice to separate rich quantities of NK cells. Clinics lacking cell biology infrastructure generally procure amniotic fluid from hospitals for direct injection into patients.