Stem cells are the body’s unspecialized cells capable of self-renewal and differentiation into multiple other cell types. These cells serve as an internal repair system, dividing to replenish other cells throughout life. Historical medical practice first recognized their therapeutic potential in the mid-20th century, long before their underlying biology was fully understood. Early applications focused on using adult stem cells to replace damaged or diseased tissues, primarily in the blood system and on the body’s surface. This history established the foundation for modern regenerative medicine.
The Foundational Use: Hematopoietic Stem Cell Transplants
The earliest and most established clinical use of stem cells began with hematopoietic stem cell transplantation (HSCT), commonly known as bone marrow transplantation. Dating back to the 1950s, this therapy was initially developed to treat patients whose blood-forming system had been destroyed, often by radiation exposure or high-dose chemotherapy. The goal was to replace the damaged bone marrow with healthy stem cells capable of producing all types of blood cells, including red cells, white cells, and platelets.
The first successful bone marrow transplant between a related donor and recipient occurred in 1956, performed by Dr. E. Donnall Thomas, who later received a Nobel Prize for his work. Early procedures were challenging due to the difficulty of finding an immunological match and controlling the severe immune reaction known as graft-versus-host disease (GVHD). By 1968, the technique was successfully extended to treat non-cancerous conditions, such as severe combined immunodeficiency syndrome (SCID), a life-threatening inherited disorder.
HSCT expanded to treat various hematologic malignancies like acute and chronic leukemias and lymphomas. It also became a curative option for severe non-malignant blood disorders, such as aplastic anemia, sickle cell anemia, and thalassemia. The procedure works by infusing healthy hematopoietic stem cells, typically collected from bone marrow, peripheral blood, or umbilical cord blood, into the patient. These cells travel to the bone marrow space, where they engraft and begin producing a new, healthy blood and immune system.
Repairing Surface Tissues: Skin and Corneal Applications
Stem cells have also been used historically to regenerate surface tissues, relying on adult stem cells found in the skin and the eye. This application focuses on repairing physical damage to the body’s protective barriers. One of the earliest uses involved epidermal stem cells, or keratinocyte stem cells, for treating severe burn victims who lacked enough healthy skin for traditional grafting.
Pioneering work in the 1970s and 1980s led to the development of cultured epithelial autografts (CEA). This technique involves taking a small biopsy of a patient’s healthy skin, isolating the epidermal stem cells, and expanding them in a laboratory culture to create large sheets of skin. These cultured sheets were then used to provide permanent coverage for massive, full-thickness burn wounds, becoming clinically established in the early 1980s.
Another historical application is limbal stem cell transplantation (LST) for repairing the surface of the eye. Limbal stem cells are located at the border between the cornea and the white of the eye, where they continuously renew the corneal surface. Damage to this area, often caused by chemical burns, can lead to limbal stem cell deficiency, resulting in chronic pain, scarring, and blindness. The first modern LST procedure, involving the transplantation of limbal tissue from the patient’s healthy eye, was reported in 1989. This procedure successfully stabilized the ocular surface and restored vision.
Historical Context of Stem Cell Types
The historical clinical applications described above, such as bone marrow transplants and skin grafts, rely exclusively on Adult Stem Cells (ASCs), also known as somatic stem cells. These cells are multipotent, meaning they can only differentiate into a limited range of cell types related to their tissue of origin. ASCs were accessible in the body, which allowed their therapeutic use to advance without major ethical or political controversy.
The discussion around stem cell usage broadened considerably with the isolation of human Embryonic Stem Cells (ESCs) in 1998. ESCs are pluripotent, possessing the capacity to become nearly any cell type in the body, which made them immensely valuable for research into regenerative medicine. However, their derivation from early-stage human embryos immediately led to intense ethical and political debates regarding the destruction of the embryo.
These ethical concerns historically influenced which types of stem cells were studied and used in the United States. Federal funding for research on new human ESC lines was restricted by executive order in 2001, limiting federally supported scientists to a small number of existing cell lines. This policy context meant that the development and historical research trajectory of ESCs were significantly constrained by federal policy and funding limitations for nearly a decade, cementing ASCs as the dominant source for early clinical stem cell success.