Stem cells are biological cells defined by two primary characteristics: the ability to self-renew and the capacity to differentiate, which allows them to mature into specialized cell types like blood, nerve, or muscle cells. This combination of properties makes them tools in regenerative medicine and disease treatment. The therapeutic application of these cells is not a recent development, but rather a field with a history spanning many decades, beginning with the successful replacement of a diseased blood system. Understanding the past uses of stem cells reveals a progression from simple cellular replacement to complex tissue engineering and attempts at organ repair.
Hematopoietic Stem Cell Transplantation
The most established clinical use of stem cells is in the treatment of blood-related disorders, a procedure historically known as a bone marrow transplant. This technique relies on hematopoietic stem cells (HSCs), which are multipotent cells capable of generating all components of the blood and immune system. The medical application of HSCs began in the mid-20th century, with the first successful transplant between identical twins to treat leukemia occurring in 1957, pioneered by physician E. Donnall Thomas.
The procedure is used to treat various malignancies, including leukemias and lymphomas, as well as non-malignant conditions like severe aplastic anemia and certain immune deficiency syndromes. Treatment typically involves ablating the patient’s diseased or dysfunctional bone marrow using high-dose chemotherapy or radiation. Healthy HSCs are then infused into the patient to repopulate the marrow and reconstitute a functional blood and immune system.
Initially, the cells were harvested exclusively from the bone marrow, but advancements led to the collection of HSCs from two other sources. Peripheral blood stem cells, mobilized from the marrow into the bloodstream, now account for the majority of transplants performed globally. Umbilical cord blood also became a viable source of HSCs, offering an alternative for patients who lack a fully matched adult donor. The development of human leukocyte antigen (HLA) matching was a major step forward, allowing researchers to identify suitable donors and significantly reducing the risk of graft-versus-host disease.
Regeneration of Surface Tissues
Stem and progenitor cells have been used for decades to repair and reconstruct surface structures, representing an application focused on localized tissue engineering. A notable historical success is the treatment of severe burns, which involves using epithelial stem cells and progenitors to create new skin. Pioneering work in the mid-1970s demonstrated that a small biopsy of a patient’s skin could be expanded in a laboratory culture to grow large, thin sheets of epidermis.
These cultured epidermal autografts (CEA) allowed physicians to treat patients with burns covering a vast percentage of their body surface area, a treatment previously impossible due to the lack of sufficient donor skin. The cells used were the patient’s own, which eliminated the risk of rejection and provided a permanent biological cover for the wound. This approach showed that adult stem cells could be harvested, manipulated ex vivo, and transplanted to restore a complex tissue structure.
Another successful application involves restoring the surface of the eye following chemical or thermal injury. The cornea’s transparent layer is maintained by limbal stem cells (LSCs). When these LSCs are destroyed, limbal stem cell deficiency (LSCD) occurs, leading to chronic inflammation and vision loss. The first clinical procedures involved transplanting an entire piece of healthy limbal tissue from a donor eye. This was later refined in 1997 with the development of Cultivated Limbal Epithelial Transplantation (CLET), a technique where LSCs from a tiny biopsy are grown in culture and then transplanted onto the damaged eye.
Historical Trials in Complex Organ Repair
The historical scope of stem cell use expanded in the early 2000s with initial attempts to repair complex internal organs. Early trials focused on the cardiovascular system, aiming to limit damage or regenerate heart tissue following a myocardial infarction, or heart attack. Researchers first explored the use of bone marrow-derived stem cells, including heterogeneous populations of bone marrow mononuclear cells (BMMNCs), which were injected into the coronary arteries or directly into the heart muscle.
These initial clinical studies demonstrated that the procedure was safe, but they also revealed a limitation: the cells did not consistently differentiate into new, functional heart muscle as hoped. Instead, subsequent research suggested the benefit might come primarily from the stem cells releasing paracrine factors, which act as signals to promote angiogenesis (new blood vessel growth) and tissue repair by other mechanisms. Although the initial promise of full cardiac regeneration was not fully realized in these early trials, they established the feasibility of delivering cells to the damaged heart and paved the way for continued research using different cell types, such as mesenchymal stem cells (MSCs).
In the neurological field, historical efforts focused on replacing specific cell types lost in neurodegenerative diseases. For Parkinson’s disease, which involves the death of dopamine-producing neurons, early trials in the 1980s and 1990s involved transplanting dopamine-rich fetal tissue directly into the brains of patients. These efforts were controversial and had mixed results, but they proved that the central nervous system could accept and integrate transplanted cells. This foundational work provided the biological and surgical framework for later clinical trials that used laboratory-derived neural stem cells to generate the specific dopamine-producing neurons needed for replacement therapy.