Exploring and Comparing Types of Cell Therapy and Its Applications

What Is Cell Therapy?

AstraZeneca defines cell therapies as a treatment that replaces damaged cells with healthy cells or an immune cell treatment that targets and removes dysfunctional cells.

Although cell and gene therapy are often lumped together, they are two distinct areas of healthcare. The definitive difference between cell therapy and gene therapy is that cell therapy introduces new cells to treat a particular health condition; however, gene therapy edits a patient’s genome to address inherited diseases.

While they can be two distinct categories, cell and gene therapy can be combined for cell-based gene therapy, such as CAR-T and modified stem cell therapy. Cell and gene therapy uses may vary and depend on the patient’s medical condition, test results, treatment goals, preferences, and availability.

According to the United States Food and Drug Administration (FDA) Center for Biologics Evaluation and Research (CBER), cell therapies may include cellular immunotherapies, cancer vaccines, and autologous or allogenic cells for therapeutic indications. Cell therapy may also refer to hematopoietic stem cells and adult or embryonic stem cells.

A 2021 article published in Frontiers in Medicine divides cell therapies into multiple categories: stem cell-based, non-stem cell-based, and multicellular therapies. Each class is divided into subcategories with different applications and uses.

Stem Cell-Based Cell Therapies

The Memorial Sloan Kettering Cancer Center defines stem cells as “immature cells that can become any type of blood cell.” Stem cells’ ability to differentiate into nearly any cell type makes them a unique tool for regenerative medicine, cell therapy, and genetic disease treatments.

An article published by DVC Stem, Louis A. Cona, MD, provided an overview of stem cell therapy and its applications. The treatment pathway often addresses autoimmune diseases, inflammatory disorders, and neurological conditions.

Moreover, stem cell research has explored stem cell-based cell therapy for hematologic malignancies, including acute myeloid leukemia (AML), acute lymphoblastic leukemia (ALL), chronic myeloid leukemia (CML), chronic lymphocytic leukemia, multiple myeloma, and myelodysplastic syndromes (MDS).

Lymphomas, including Hodgkin’s and non-Hodgkin’s lymphoma, and bone marrow failure syndrome, such as aplastic anemia, paroxysmal nocturnal hemoglobinuria (PNH), Fanconi anemia, and pure red cell aplasia, can be treated using a stem cell transplant.

Additionally, clinical studies have explored various types of stem cell transplants that can be used to address the following conditions:

• Inherited immune system disorders: severe combined immunodeficiency (SCID), Wiskott–Aldrich syndrome, and chronic granulomatous disease
• Autoimmune disorders: systemic lupus erythematosus (SLE), multiple sclerosis (MS), rheumatoid arthritis, Sjogren’s syndrome, and system sclerosis
• Neurological disorders: Parkinson’s disease, Alzheimer’s disease, amyotrophic lateral sclerosis (ALS), spinal muscular atrophy (SMA), stroke, traumatic brain injury (TBI), and spinal cord injury
• Cardiovascular disease: ischemic heart disease (myocardial infarction), dilated cardiomyopathy, congestive heart failure, and peripheral arterial disease
• Diabetes: types 1 and 2 diabetes
• Liver disease: cirrhosis and acute liver failure
• Kidney diseases: chronic kidney disease and acute kidney injury
• Lung diseases: chronic obstructive pulmonary disease (COPD), idiopathic pulmonary fibrosis, and cystic fibrosis
• Musculoskeletal and connective tissue disorders: osteoarthritis, cartilage defects, osteogenesis imperfecta, bone fractures, and nonunions
• Gastrointestinal disorders: Crohn’s disease, ulcerative colitis, graft-versus-host disease (GVHD)
• Skin disorders: severe burns and epidermolysis bullosa
• Ocular diseases: age-related macular degeneration, retinitis pigmentosa, and corneal diseases

DVC Stem identifies six main of medical applications for stem cells: tissue regeneration and repair, new drug discovery and testing, disease modeling, gene therapy and editing, immunotherapy, and personalized medicine.

Types of Stem Cells

Multiple sources of stem cells comprise the different types used for treatment, including human embryonic stem cells — derived from human embryos, adult stem cells, and induced pluripotent stem cells (iPSCs).

Embryonic stem cells (ESC) are extracted from the inner cell mass of a blastocyst. These cells can also be called human pluripotent stem cells, which, unlike multipotent stem cells, can differentiate into many different cell types.

According to DVC Stem, “Embryonic stem cells are typically grown in the laboratory as "stem cell lines," which are cultures of human cells that can be maintained and expanded to increase the total amount of pluripotent stem cells. Several lines of human embryonic stem cells have been established and used for research purposes.”

Adult stem cells are adult cells that have not been differentiated into specific cell types despite being surrounded by specialized cells. Researchers and clinicians can extract these cells from a variety of adult tissues. These cell types are multipotent and have a limited differentiation ability.

Hematopoietic stem cells are adult stem cells that produce blood cells and mesenchymal stem cells.

Mesenchymal stem cells (MSCs) are adult cells that can be differentiated into multiple cell types, including bone, cartilage, and fat. DVC Stem notes that these cell types are immunomodulatory, anti-inflammatory, and have self-renewal properties. These stem cells are derived from adipose tissue, bone marrow, umbilical cord blood and tissue, liver, dental pulp, and skin. They can also be used as progenitor cells undergoing in vitro fertilization to create more stem cells in the laboratory.

Induced pluripotent stem cells are genetically modified adult cells that mimic embryonic stem cells often used for autologous transplants.

Non-Stem Cell-Based Cell Therapies

Unlike stem cell therapies, non-stem cell-based cell therapies use somatic cells, such as fibroblasts, chondrocytes, keratinocytes, hepatocytes, pancreatic isle cells, and immune cells. According to the Frontiers article, “Somatic cell-based therapies are generally employed as an in vivo source of enzymes, cytokines, and growth factors; as an adoptive cell therapy (ACT) to treat cancers; as transplanted cells, such as hepatocytes or pancreatic islet cells, to correct inborn metabolic errors; or as scaffold-based or -free cellular systems to treat ulcers, burns, or cartilage lesion.”

One vital type of ACT is chimeric antigen receptor T-cell therapy, also known as CAR-T cell therapy, which uses autologous T-cells, modified to express CARs on the cell surface, to attack and kill tumor cells.

In August 2017, the United States Food and Drug Administration (FDA) approved the first-ever CAR-T cell therapy, Kymriah — a treatment for acute B-cell lymphoblastic leukemia (ALL), which Novartis manufactured.

Later that year, in October 2017, Gilead and Kite Pharma secured FDA approval for Yescarta, a CAR-T cell therapy for subtypes of non-Hodgkin’s lymphoma (NHL): diffuse large B-cell lymphoma (DLBCL) and primary mediastinal large B-cell lymphoma (PMBCL).

Multi-Cellular Therapies

Multi-cellular therapies can combine multiple different kinds of cell therapy. At a minimum, multi-cellular treatments require two types of stem cell or non-stem cell therapy. These protocols may involve both types of treatment. Multi-cellular therapies may include ACT products, scaffold-based or free cellular products, stromal vascular fraction (SVF), stem cell transplant (sometimes called bone marrow transplants), and bone marrow aspirated (BMA)-derived therapies.