Cell Therapy - History

History

Cellular (cell) therapy can be defined as the use of cells to treat disease. Its origins can be traced to the early 1800s, when Dr Charles-Edward Brown-Séquard (1817–1894) injected animal testicle extracts to stop the effects of aging, followed by Paul Niehans (1882–1971), who practiced cell therapy using calf embryo cells in Switzerland.

Modern cellular therapy obtained its scientific legitimacy mainly from the field of bone marrow transplantation. The first breakthrough was provided by Prof Jean Dausset who in 1952 performed the experiments that lead to the identification of the first of many HLA antigens on the surface of cells. The understanding that HLA antigens are the body’s identification and when it does not recognize the patterns of an HLA antigen an immunological response is initiated, opened the field of allogeneic bone marrow transplantation. Dr Dausset's discovery and continuous work granted him the Nobel Prize in Physiology or Medicine in 1980. In the late 1950s his discoveries led to the first successful transplant of cells between identical twin patients. The transplant was performed by Dr E. Donnall Thomas, who went on to receive the Nobel Prize in physiology or medicine in 1990.

The consequence of such discoveries was the achievement of additional milestones in the area of cell transplantation and in 1968, in Minnesota, the first successful non-twin (allogeneic) transplantation took placed followed by the first unrelated bone marrow transplant in 1973, when a boy with a genetic immunodeficiency disorder received multiple marrow transplants from a donor identified as a match through a blood bank in Denmark.

While cellular compatibility issues were being deciphered, the cell therapy area continued to bloom. Stem cells from cord blood were successfully transplanted in 1988, in Paris, when it was used for the first time to regenerate blood and immune cells on a 6-year-old boy suffering from Fanconi anemia, a blood disorder, and in 1997 a successful cord blood transplant was performed on an adult suffering from chronic myelogenous leukemia using cord blood cells that were expanded ex vivo, which means outside of a living organism.

Another scientific leap occurred in 1998, when James Thompson from the University of Wisconsin – Madison developed the first embryonic stem cell lines. The capacity to generate different cell types from a common cell ancestor under control conditions and the increase understanding on how to grow cells ex-vivo, boosted the basic research and development of potential cell products in the field of regenerative medicine. Initially the studies were aimed at replacing cells that were damaged by disease with cells grown ex-vivo, however the field evolved and cells are instead used as secretors of factors that can ameliorate or change the course of disease. Due to the ethical controversy associated with the use of embryonic cells for research purposes, the field suffered a temporary setback, however in 2006, Shinya Yamanaka's team at Kyoto University, Japan first generated induced pluripotent stem cells (iPSCs) from mouse fibroblasts and in November 2007, James Thomson at University of Wisconsin–Madison and Shinya Yamanaka and colleagues, reported the production of iPSCs from adult human cells. This scientific discovery serves as a catalyst for new research in the area of regenerative medicine and diagnostics based on cellular therapies. During the last 20 years stem cells and adult cells derived from different tissues such as blood, bone marrow, muscle, brain, hair, skin, etc., have been characterized, grown in culture and tested in animals and in the clinic for a diverse number of illnesses.