Stem Cell Therapies – Reality vs. Hope and Hype

By Nasser Ayyad DO (Updated: 11/1/2021)

Introduction

Nearly every day, the practitioners at Desert Spine and Sports Physicians are asked by patients about regenerative medicine treatments, such as stem cell therapy for musculoskeletal complaints affecting the hip, knee, shoulder, back, neck, and more. Because humans are living longer and longer, there is a growing number of people with osteoarthritis and tendinosis, that is driving a need to develop therapies that not only address the painful symptoms but also prevent the progressive destruction of joints and soft tissues.

Scientists, doctors, and patients are excited about stem cells for an obvious reason, as they appear to have the potential to help repair or replace damaged tissue. Treatments with stem cells are booming in the U.S. and internationally, with clinics offering treatment for conditions ranging from arthritic knee pain, to multiple sclerosis, to erectile dysfunction. But the U.S. Food and Drug Administration (FDA) is concerned that some patients seeking cures and remedies are vulnerable to stem cell treatments that may be illegal, ineffective, costly, and potentially harmful. To ensure that the emerging field of stem cell therapy fulfills its promise to patients, we must develop a solid understanding of the basic science of stem cells, educate ourselves on the risks and benefits, and employ safe and effective treatments.

What Are Stem Cells?

Stem cells are the body’s master cells. All other cells arise from stem cells, including muscle cells, nerve cells, blood cells, and others. Stem cells have two key properties: 1) the ability to self-renew in order to ensure a steady supply of replacement cells for those lost to disease, injury, and age, and 2) the ability to differentiate into diverse specialized cell types such as heart, brain, and bone cells. There are three basic types of stem cells: 1) embryonic stem cells, 2) non-embryonic (adult) stem cells, which include mesenchymal and perinatal (amniotic fluid and umbilical cord) stem cells, and 3) induced pluripotent stem cells. The two main sources of stem cells are autologic (from yourself) or allogenic (from a donor). For a full description of the different stem cells and their sources, see the glossary at the end of this blog.

Approved Stem Cell Therapies

To date, the only stem cell therapy explicitly approved by the FDA for use in the U.S. consists of versions of bone marrow/hematopoietic (blood) stem cell transplantation for cancer and other specific blood-related disorders. This means that any other stem cell treatment you see advertised on the internet or elsewhere is not FDA-approved. The exceptions to this are if the stem cell treatment is part of an FDA-approved clinical trial or if the treatment is using stem cells in a procedure that meets other criteria. California’s Stem Cell Agency provides a detailed list of the disease programs and clinical trials currently underway in stem cell research.

In August 2017, the FDA announced that when stem cell products are used in unapproved ways or when they are processed in ways that are more than minimally manipulated, which relates to the nature and degree of processing, they have the authority to take action to protect the public’s health. To learn more about the FDA’s oversight of stem cell therapies, see FDA Commissioner Scott Gottlieb, MD’s statement and the most recent FDA Consumer Advisory Statement.

Evidence

According to an article published in March 2017 by the FDA in the New England Journal of Medicine, the assertion that stem cells are intrinsically able to sense the environment into which they are introduced and address whatever functions require replacement or repair – whether injured knee cartilage or a neurologic deficit – is not based on scientific evidence. Moreover, published data derived primarily from small, uncontrolled studies in addition to a few randomized controlled trials (RCTs), have not reliably demonstrated the effectiveness of stem cell treatments. This was shown by researchers at the Mayo Clinic, who published an RCT in August 2016 on bone marrow stem cell therapy for arthritic knee pain. While no complications were observed in the study, patients surprisingly experienced similar levels of pain relief whether they received stem cells or saline (salt water). The authors concluded that while apparently safe, stem cell injections cannot yet be recommended for routine care of knee arthritis.

Stem cell therapies for chronic spine pain have also demonstrated similar findings. For example, an RCT published in 2017 evaluated intradiscal injection of allogeneic mesenchymal bone marrow stem cells for the treatment of chronic back pain due to degenerative disc disease (DDD). While the stem cell-treated discs did show marginally improved quality on follow-up imaging, the researchers found no difference in level of pain relief or functional improvement compared to sham injection.1 A more recent study, published in 2020, retrospectively evaluated bone marrow aspirate concentrate (often referred to as BMAC) for the treatment of lumbar DDD. Thirty-three patients underwent intradiscal injection of BMAC, and researchers found pain decreased by at least 50% in nearly half of the patients at six weeks post-injection. However, this declined to less than one-quarter of patients by six months. There were no significant complications reported.² Again, while apparently safe, these studies and others are limited by the small number of patients, lack of scientific rigor, and overall poor quality of evidence. Further research is needed to determine the regenerative potential of stem cells for knee arthritis, DDD, and other musculoskeletal disorders affecting the cartilage, tendon, and other soft tissues in the body.

The Future of Stem Cells and Regenerative Medicine

Stem cells have tremendous potential to help us understand and treat a range of diseases, injuries, and other health-related conditions. Excitement about the potential for new stem cell therapies has obscured the fact the scientific evidence for these treatments has lagged far behind the hype. Therefore, stem cell treatment should be viewed as experimental in nature rather than standard practice. Moving forward, it is critical that the regenerative medicine field develop standards and oversight while simultaneously encouraging research and innovation to ensure that patients have access to safe and effective treatments as efficiently as possible.

Questions to Ask Before a Stem Cell Procedure

• Is the treatment routine for this specific disease or condition? What is the scientific evidence that this new procedure could work for my disease or condition? Where is this published?
• What are the alternative treatment options for my disease or condition?
• What are the possible benefits I can expect? How will this be measured, and how long will this take?
• How is this stem cell procedure done?
• What is the source of the stem cells?
• If the cells are from a donor, what will prevent my immune system from reacting to the transplanted cells?
• Is there any independent oversight or accreditation of the clinic where the treatment will be done and the facility where the cells are processed?
• Is there approval from a national or regional regulatory agency, such as the U.S. Food and Drug Administration (FDA) or European Medicines Agency (EMA), for this treatment of this specific disease?

GLOSSARY

Origins and Types of Stem Cells

Embryonic Stem Cells: These stem cells are obtained from early-stage embryos, a group of cells formed when a woman’s egg is fertilized with a man’s sperm; this process takes place at an in vitro fertilization clinic with the informed consent of donors who donate their eggs and sperm for research purposes. These stem cells are pluripotent, meaning they are capable of developing into any type of cell in the human body and can divide indefinitely. This versatility gives embryonic stem cells the potential to regenerate or repair diseased tissue and organs. In 2009, President Barack Obama issued Executive Order 13505, allowing the Secretary of Health and Human Services, through the Director of the NIH, to support and conduct responsible human stem cell research, including human embryonic stem cell research.

Non-embryonic (Adult) Stem Cells: Adult stem cells have a misleading name because they are also found in infants and children. Adult stem cells are multipotent, meaning they can generate a few different cell types, generally in a specific tissue or organ. There are many different types of adult stem cells that are located in the body, including the brain, teeth, blood vessels, skin, skeletal muscles, liver, bone marrow, heart, peripheral blood, and fat. For example, hematopoietic (blood) stem cells are found in the bone marrow; they give rise to red blood cells, white blood cells, and platelets. Neural stem cells are another type of adult stem cell and are found in the nervous system.

Mesenchymal stem cells (MSCs) are a type of adult stem cell found in adipose (fat) tissue, bone marrow, and the blood. These cells have the potential to form bone, cartilage, muscle, tendon, and fat. Scientists are investigating how MSCs might be used to treat bone and cartilage diseases. Bone marrow aspirate concentrate (BMAC) is a common source for harvesting mesenchymal stem cells. BMAC is currently approved by the United States Food and Drug Administration and represents one of the few means for acquiring stem cells for subsequent injection.

Perinatal stem cells are a type of MSC derived from amniotic fluid and umbilical cord blood (i.e., Wharton’s Jelly). Cord blood is usually discarded after delivery, however, if taken with the permission of the parents, these multipotent cells can be donated for research and treatment.

Induced Pluripotent Stem Cells: These stem cells are another type of pluripotent stem cell. While embryonic stem cells are derived from the early embryo, induced pluripotent stem cells are created when adult stem cells are reprogrammed to become like embryonic stem cells. By culturing (growing) adult cells in the laboratory in the presence of genes which are functional in the early embryo, the adult genes are switched off, and the cells’ embryonic genes switched on. Like embryonic stem cells, these induced pluripotent stem cells are capable of developing into any cell type in the body.

Stem Cell Sources:

There are two main sources of stem cells used for stem cell treatments. If you have an autologous (or autograft) transplant, you receive your own stem cells that were collected before your treatment started. An example of autologous stem cells are mesenchymal stem cells harvested from one’s bone marrow and then used as treatment in an arthritic joint. An advantage of autologous stem cell transplant is that you’re getting your own cells back, so you don’t have to worry about the stem cells attacking your body or about getting an infection from another person.

Allogeneic stem cells come from a donor, such as stem cells from an umbilical cord or another person.  Allogeneic stem cells are most often used to treat certain types of blood cancers, such as leukemia and multiple myeloma. In these cases, the advantage of allogeneic stem cell transplantation is that the donor stem cells make their own immune cells, which help destroy any cancer cells that may remain after cancer treatment. The potential challenge associated with donor stem cells is that they can die or be destroyed by the patient’s immune system before transforming into new tissue. On the other hand, immune cells from the donor can also attack cells in the patient’s body, which is called graft-versus-host disease. There is also a very small risk of certain infections from donor cells.

References:

1. Noriega DC, Ardura F, Hernández-Ramajo R, Martín-Ferrero MÁ, Sánchez-Lite I, Toribio B, Alberca M, García V, Moraleda JM, Sánchez A, García-Sancho J. Intervertebral Disc Repair by Allogeneic Mesenchymal Bone Marrow Cells: A Randomized Controlled Trial. Transplantation. 2017 Aug;101(8):1945-1951.
2. Wolff, M., Shillington, J.M., Rathbone, C. et al. Injections of concentrated bone marrow aspirate as treatment for Discogenic pain: a retrospective analysis. BMC Musculoskelet Disord 21, 135 (2020).