Throughout its long history, medicine has made continuous and significant progress. From the early observations of Greek physicians – such as Hippocrates, widely considered the father of medicine – to the discoveries of later centuries, these advances have shaped what we now recognise as modern medicine.1 

In the late 1960s, organ transplantation represented a major therapeutic milestone. At that time, replacing a diseased organ with a healthy donor organ was considered one of the highest achievements in medicine, despite the technical challenges and the ongoing risk of immune rejection.2 

Today, regenerative medicine has entered both diagnostic and therapeutic fields and continues to gain ground. In simple terms, it builds on the body’s natural ability to repair damage, using biological elements generated by the organism itself. 

Defining regenerative medicine  

Regenerative medicine represents an important development in the treatment of diseases, particularly those of a degenerative nature. Degeneration should be understood not only as disease affecting organs, but also as the progressive changes associated with ageing and the natural decline of biological systems.3 

This approach therefore goes beyond the treatment of symptoms, aiming instead to restore or regenerate tissues, cells and, in some cases, organs. To achieve this, regenerative medicine draws on advances in molecular biology and cellular science, including the study of stem cells, mononuclear cells and platelets.4 

One of its most distinctive characteristics is the ability to stimulate processes that are already present within the body, encouraging repair through intrinsic biological mechanisms. In this sense, the organism itself becomes an active participant in the healing process. 

Regeneration in myth and early thought 

The idea of regenerating the human body has long existed within human imagination. In classical Greek and Roman mythology, regenerative abilities were often attributed to gods, demigods and mythical creatures.5 

Examples include Antaeus, who was said to heal every wound on his body through contact with the earth, and the Lernaean Hydra, a venomous nine-headed aquatic serpent, capable of regrowing multiple heads when one was removed (Figure 1).5 These narratives represent early attempts to interpret regenerative phenomena, placing them within a symbolic or supernatural framework. 

The sense of awe surrounding regenerative phenomena remains evident today, even as mythological explanations have given way to scientific understanding. Over time, the fictional elements associated with these narratives have diminished, while their symbolic value has persisted. The regenerative qualities of the Hydra, for example, have been widely adopted as a metaphor: Erasmus of Rotterdam used the creature to represent the persistence of war, while counterrevolutionary movements in late 18th- and early 19th-century France employed it pejoratively to describe the Revolution’s capacity to repeatedly re-emerge.5 In this way, regeneration has come to signify not only biological renewal, but also resilience, recurrence and transformation. 

Figure 1: A depiction of Lernaean Hydra, a venomous nine-headed aquatic serpent, capable of regrowing multiple heads when one was removed. 

Aristotle and the foundations of biological observations  

If classical mythology confined regenerative capacity to the realm of the supernatural, it was with the philosophical and scientific reflections of Aristotle (384–322 BC) that these observations began to be brought into a more rational framework.6 The philosopher sought to understand living systems through systematic observation, aiming to explain not only what occurs in nature, but why it occurs. 

Among the most relevant works in this context is Historia Animalium, a foundational text in early zoology, in which Aristotle documented a wide range of biological phenomena (Figure 2).6,7 Within this work, he described the ability of certain animals to regenerate lost body parts, including the regrowth of a lizard’s tail. While limited by the scientific knowledge of the time, such observations represent one of the earliest attempts to interpret regeneration as a natural process rather than a supernatural event. 

Aristotle’s broader philosophical framework proposed that the principles governing life are inherent within living matter itself, rather than imposed externally. This idea anticipates a central concept of modern regenerative medicine: that organisms possess intrinsic mechanisms capable of supporting repair and renewal. 

The influence of Aristotle’s naturalistic studies persisted for centuries. Even in the 16th century, zoologists such as Konrad Gessner continued to build upon Aristotelian descriptions of the natural world, further documenting regenerative phenomena in animals.7 

While Aristotle’s work cannot be considered scientific in the modern sense, he recognised a fundamental property of living systems – the capacity for regeneration – which would later become central to biological and medical research. 

Figure 2: The 1619 BEIC edition of Historia Animalium by Aristotle (originally published c.343-340 BC). 

Early scientific observations of regeneration  

The more distant history of regenerative medicine includes important contributions from 18th-century naturalists. Among them, Lazzaro Spallanzani (1729-1799), Professor of Natural History at the University of Pavia, carried out detailed experimental observations on regenerative phenomena.8 

In his work Dissertazioni di fisica animale e vegetabile (1780), Spallanzani described regeneration in several species, including snails (regrowth of horns), lizards (tails) and amphibians such as frogs (limbs). Although he was unable to fully explain the biological mechanisms underlying these processes, his work demonstrated that regeneration was a reproducible natural phenomenon. 

These observations were complemented by those of other 18th-century scholars, including René Antoine Réaumur and Jean-Étienne Guettard, who further documented regenerative processes in animals and contributed to the growing body of scientific knowledge in this area.9 

Figure 3: René-Antoine Ferchault de Réaumur’s Mémoires pour servir à l’histoire des insectes published in 1712.  

The transition to cellular understanding  

It was in the 19th century that regenerative phenomena began to be more closely associated with cellular biology. Early theories proposed that cells themselves possessed regenerative potential, shifting the focus from whole organisms to their fundamental structural units.10 

In 1892, Jacob Keller suggested that cells held intrinsic regenerative capacity. His ideas were later developed through the work of researchers such as Giulio Bizzozero (1846-1901) and Alexander Maximow (1874-1928), who contributed to the understanding of cellular lineage, particularly within the blood system.11 

These developments ultimately led to the concept of a common origin for blood cells and laid the groundwork for later discoveries. In the mid-20th century, Alexander Friedenstein identified mesenchymal stem cells, providing further evidence of the body’s capacity for cellular regeneration.12 

The emergence of modern regenerative medicine  

The contemporary concept of regenerative medicine began to take shape in the late 20th and early 21st centuries, supported by advances in molecular biology, genetics and biotechnology. 

A key milestone occurred in 2004 with the establishment of the California Institute for Regenerative Medicine, following the approval of Proposition 71 in the United States (Figure 4).13 This initiative allocated $3 billion in public funding to support research into stem cell biology and regenerative therapies, marking one of the most significant governmental investments in the field.13 Beyond its financial impact, the programme also played an important role in legitimising regenerative medicine as a defined area of scientific and clinical focus, accelerating both basic research and the translation of emerging therapies into clinical practice. 

Today, regenerative medicine encompasses a range of approaches, including cell therapy, tissue engineering, gene therapy and the development of biomaterials and medical devices. These strategies aim not only to treat disease, but to restore structure and function by activating or supporting the body’s own repair mechanisms. 

Applications are being explored across multiple clinical areas, including cardiovascular, musculoskeletal, neurological and soft tissue conditions, reflecting the broad potential of this evolving field. 

Figure 4: The Lorry I. Lokey Stem Cell Research Building at Stanford University, one of the largest California Institute for Regenerative Medicine facilities. Image copyright of Mark Tuschman.  

From imagination to intervention  

The concept of regeneration has evolved over time from mythological imagination to scientific reality. What was once attributed to supernatural forces is now understood as an intrinsic property of living systems, supported by increasingly sophisticated biological knowledge. 

Although regenerative medicine does not eliminate ageing or disease, it represents an important shift in medical thinking – from replacement and symptom management toward restoration and biological repair. As research continues to advance, it is likely to play an increasingly central role in the future of medicine.