Mesenchymal Stem Cells

In 1991, Professor Arnold Caplan published the seminal paper, Mesenchymal Stem Cells (MSCs). In the article, he described MSCs as having the ability to differentiate and self-renew into multiple tissue types, as well as neurons and blood vessels. ^[1] In other words, they are ‘multipotent,’ meaning they can produce more than one type of specialized cell of the body, but not all types. Differentiation and self-renewal are the unique characteristics required of a cell to be a stem cell.

In the article’s introduction, he called MSCs, “the basis for the emergence of a new therapeutic technology of self-cell repair” (emphasis added). His tireless research gained extensive support from hundreds of other scientists. In fact, according to a PubMed search, there are now over 160,000 published papers that discuss MSCs. This vast body of literature has led to a broad agreement as to how these repair cells migrate to and repair diseased tissues and organs. The science has also progressed to include an understanding as to how MSCs restore normal function in our vascular, immune, and endocrine (hormone) systems.

Research has further progressed to include an appreciation of how MSCs do their job (and has led to a proposed new name for them). More on the new name later; first, here is the back story.

Biodistribution

Since the early days of research into MSCs, scientists have been on a quest to determine the optimum delivery route. Much like planning the most efficient course through a labyrinth-like city (such as London), they want our stem cells to stay clear of blind alleys, wrong-way streets, and circuitous routes. The investigators also recognize some courses may be riskier than others – even if seemingly more efficient per the map, e.g., directly injecting stem cells into the brain or the eye.

But there is a new angle to the planning process that is increasingly appreciated by researchers: The underlying role that low-level systemic inflammation (inflammaging) plays in chronic disease and the potential for stem cells to calm that down. More on inflammaging later; first, how do MSCs do their job?

Mechanisms of Action

Mechanism of action (MOA) refers to the way our stem cells (or drugs) produce their effect. In the case of MSCs, their MOAs are analogous to the fire department: They respond to a fire alarm – i.e., an inflammatory signal – and beeline to the source of it. MSCs have been called “guardians of inflammation.” ^[2] Once they get to the scene of the fire, they release hundreds of bioactive signaling molecules called “cytokines.” The cytokines activate the local cells in the neighborhood to do their jobs. This cell-to-cell communication is called the paracrine effect.

In short, since Dr. Caplan’s groundbreaking paper was published, researchers have verified that homing and the paracrine effect are the central roles of MSCs in the repair process. And so, that is why Prof. Caplan proposed changing the name to “Medicinal Signaling Cells.” ^[3]

Biodistribution Studies

Biodistribution studies have established that adult stem cells delivered IV migrate through the lungs and “park” there (“first-pass effect”) – and then move on. (There is some confusion as to whether the first-pass effect is a “dead-end street,” but suffice to say, research has established that it is not the case.) ^{[4] [5] [6]}

As they continue on their mission to fight inflammation and repair the body, they journey through the vascular system and organs to the spleen, our largest immune organ. They then route through the lymphatic system.

The lymphatic system, which runs parallel to the vascular system, is an essential part of the immune system. It carries lymph (a clear fluid containing a high number of a type of white blood cells called lymphocytes. Lymphocytes fight infection and destroy damaged or abnormal cells. They are abundant in the mixed population of cells accessed from our adipose tissue for cellular therapies.

Biodistribution Studies

A well-designed study of IV infusion of adult stem cells in baboons tracked the migration. The graph below shows distribution to all of the major internal body organs. ^[7]

Add to that, in a cardiac cell therapy study, researchers at Texas Heart Institute and MD Anderson tracked stem cells injected in the hearts of pigs. They also found the MSCs traveled through the blood vessel system into the spleen and then continued to move through the lymphatics. ^[8]

As a side note, lest we discount the potential of self-cell repair, a study in mice found that systemically delivered adult stem cells could repair chemically-induced corneal damage – without there being any of the MSCs directly applied to the cornea. ^[9]

Summary
For more on why AMBROSE accesses the MSCs and other regenerative cells from your adipose tissue, please read Why Adipose Tissue. Connecting this back to our Areas of Focus and Our Protocol, ADRCs, delivered IV, have the potential to home to all of the major organs and initiate a process of repair.

Chronic systemic inflammation (CSI) is a hot topic. This is for good reason as it is nearly universally agreed that CSI is a culprit in all chronic diseases of aging.

Major media outlets like the Washington Post and New York Times have featured stories on CSI. Raw and Red-Hot, summarized some of Harvard Medical School’s (and their affiliated institutions) enlightening studies on the subject.

By accessing the stem cells (and other regenerative cells) in our fat (adipose tissue), under the auspices of the Federal Right to Try Act of 2017, those with debilitating chronic systemic inflammatory conditions have access to a new option to improve their quality of life. You can read more about the Right to Try Act here.

But is inflammation all there is to it?
The intense focus on chronic inflammation (also known as “inflammaging”) has, in many instances, served to deemphasize (or even ignore) the other factors that are also commonly involved in chronic diseases. More on that in a moment; first the story of inflammation and the largely untold story of the biggest unmet need in healthcare – patients with multiple chronic diseases.

Inflammation
Inflammation isn’t a new idea. It has a long and colorful story. Egyptian papyri from almost 5,000 years ago refer to heat and redness as naturally associated with disease. From another angle, in the 5th century BC, Hippocrates described the beneficial side of inflammation as an early component of the healing process after tissue injury.

Put in everyday terms, short-term increases in inflammation (acute) are critical to repair, and even survival, in the event of physical injury and infection, respectively.

However, it has been revealed that certain social, environmental, trauma-related and lifestyle factors can cause inflammation to go out of control and become chronic. Chronic inflammation is like a smoldering fire inside the body; it slowly spreads, often igniting multiple chronic diseases (morbidities). Patients with multiple morbidities represent the most vexing problem in healthcare.

Given the broadscale recognition of the detrimental effects of inflammaging, there is an irrepressible movement in healthcare (including patients) to do something about it. Conventional doctors prescribe drugs to suppress inflammation, while integrative physicians recommend diets and supplements to tamp it down. Increasingly people (from the “worried well” to the chronically ill) drink green juices and eat kale salads to replace the sugary drinks, bread and desserts they were previously “enjoying” at the expense of their health.

Not to be left out, scientists are researching the pathways and genes in the body that turn excess inflammation on with the hope of discovering small molecules that can be put in a pill to turn it off like a light switch.

But, regardless of all that – and even with some people reporting benefits – the onslaught of chronic diseases of aging has not been reversed nor the prescriptions of drugs, surgeries and devices to fight them slowed.

The Plus Side
On the plus side, for more than 20 years hundreds researchers have described in more than 10,000 peer-reviewed papers, that a mixed population of stem and regenerative cells found in our fat (adipose tissue) can not only improve inflammatory markers, but also address the multiple factors that contribute to the ill health that resulted from inflammaging.

In 2016, researchers summarized the science and studies supporting the unique attributes of ADRCs in a review paper, Autologous Adipose Derived Regenerative Cells: A Platform for Therapeutic Applications.

Trish’s remarkable patient-reported outcome for “hypermobility”, an inherited connective tissue disease, is a profound example of the potential of benefits of AMBROSE Cell Therapy. Her condition had resulted in chronic inflammation, debilitating pain and disability. Unlike others in her family with the same condition, Trish is now able to live life to the fullest. Here is her story.