Tissue engineering and regenerative medicine: semantic considerations for an evolving paradigm

Abstract

Tissue engineering (TE) and regenerative medicine (RM) are rapidly evolving fields that are often obscured by a dense cloud of hype and commercialization potential. We find, in the literature and general commentary, that several of the associated terms are casually referenced in varying contexts that ultimately result in the blurring of the distinguishing boundaries which define them. "TE" and "RM" are often used interchangeably, though some experts vehemently argue that they, in fact, represent different conceptual entities. Nevertheless, contemporary scientists have a general idea of the experiments and milestones that can be classified within either or both categories. Given the groundbreaking achievements reported within the past decade and consequent watershed potential of this field, we feel that it would be useful to properly contextualize these terms semantically and historically. In this concept paper, we explore the various definitions proposed in the literature and emphasize that ambiguous terminology can lead to misplaced apprehension. We assert that the central motifs of both concepts have existed within the surgical sciences long before their appearance as terms in the scientific literature.

Keywords: commercialization; device regulation; organ bioengineering; regenerative medicine; stem cells; tissue engineering.

Figure 1

A diaphragmatic illustration of the relationship between regenerative medicine (RM) and tissue engineering (TE). Though RM is a broader and more generalized field than TE, one does not wholly encompass the other. Both seek to restore function, but TE is more narrow in its focus and does not require cellular regeneration. Nevertheless, taken together, RM/TE has grown to resemble a singular research entity.

Figure 2

Phases in the history of regenerative medicine. When observing the evolution of regenerative medicine era, three phases can be identified. The first phase spans from the early days to the 1970s. In those days, Alexis Carrel and Charles Lindbergh for the first time had the idea of growing organ outside the human body. For those visionary experiments, Carrel should be referred as father, pioneer, and precursor of concepts that are currently being developed in modern regenerative medicine. In those days, biology was “cytocentric” and cells were considered to be the only relevant players in the biology of complex viable systems. Things changed when it was understood that actually the extracellular matrix is as important as cells, in organ welfare; this intuition allowed transition to the second phase which spans from the 1970s to the discovery of stem cells. This intuition was conceptualized by the iconic Harvard mouse, which represents the paradigm of new ideas that paved the ground for a breakthrough in the history of medicine, namely, the bioengineering and implantation of relatively simple body parts like vessels, segments of the urinary tract, and upper airways, bones, skin, and cornea. The third phase began with the discovery of stem cells, wherein the term regenerative medicine has been coined. The discovery of stem cells made us realize that, despite complex organisms like mammals have lost during phylogenesis their ability to regenerate in full their body parts, yet, these cells – if manipulated appropriately – may re-confer us this quiescent ability. In fact, the ultimate goal of regenerative medicine is to max out the regenerative, reparative potential intrinsic to the human body [adapted from Katari et al. (2014), with permission].