Science is almost exclusively concerned with the “accessible unknown”; that is, what can be investigated using the current knowledge as a starting point. In other words, scientists only address — and talk about — questions they have a chance to answer using available tools and knowledge. If a subject is too far from what we know at a given time, we assign it to the realm of the distant future, science fiction, or metaphysics.

Thus, it is good news that, in the last twenty years or so, scientists have begun to talk openly about regenerative medicine. Once an esoteric subject for a few eccentric biologists working with animals such as hydras, planarians, or newts, regeneration has now gained the status of a respectable branch of biology — and medicine. It all started from the observation that a few privileged animals can regenerate some or all parts of their bodies and from the obvious ensuing question: if they can do it, why can we not?

The label “Regenerative medicine” refers to a variety of therapeutic approaches that aim at replacing or regenerating human cells, tissues or organs, to restore or establish normal function (Mason and Dunnill, 2008). Thus, it encompass apparently disparate strategies, including cell replacement therapy, construction of biological replacement parts in the laboratory, and enablement of dormant repair mechanisms to heal otherways irreparable tissues or organs. Current or envisioned regenerative medicine strategies often exploit stem cells from different sources.

In the last few decades, we have witnessed several revolutions in biology, many of which make possible previously inconceivable regenerative medicine approaches, hence allowing this field to enter biology’s and medicine’s mainstreams.

One breakthrough of great moment is the discovery and isolation of stem cells from the embryo, the germline, and tissues throughout the adult body. We are progressively learning more about their locations, behavior, properties, and multilineage potential. Several stem cells types, e.g., the hematopoietic and epidermal ones, are already part of established medical treatments, while many others are approaching the bedside. Altogether, stem cells constitute an important part of regenerative medicine’s raw materials.

Another revolution has been the realization that the fate of somatic cells is far from being irreversibly fixed as we once thought. In 2006 we were announced the “miracle” conversion of differentiated cells into pluripotent ones by the expression of four or fewer transcription factors (Takahashi and Yamanaka, 2006). As if this were not enough, it has just been reported that, astonishingly, somatic cells can spontaneously undergo a similar transformation in response to certain stress conditions (Obokata et al., 2014). Regenerative medicine benefits from all this, as cells with flexible fates multiply the potential building blocks for tissue renewal and repair.

One final, major advancement is the increasing awareness that stem and stem-like cells have marvelous self-organizing capacities. Here, the winning strategy is the use of aptly devised three-dimensional cultures, where cells can deploy their full potential. Using this simple trick, it has been possible to grow in the laboratory complex structures such as the intestinal epithelium, complete with villi and crypts (Sato et al., 2009), the eye retina (Eiraku et al., 2011), and cerebral organoids recapitulating many features of the human brain (Lancaster et al., 2013). Thus, we can plausibly envisage reconstructing lost tissues or organs in the adult by injecting suitable precursor cells into the lesion. The cells, it is legitimate to hope, will know what to do.

Biotechnology builds on biological advancements and adds to them. One promising strategy is that of acquiring a perfect organ “scaffold” by simply eliminating the cells of a natural organ and retaining its extracellular matrix frame. Such scaffold is then repopulated using cells obtained from the patient or a compatible donor. In principle, these “bioartificial” organs should be perfect replacements for the original one and far outperform conventional prostheses. Despite multiple biological and technical hurdles, scaffold repopulation is being used to reconstruct a wide variety of organs, including the heart, kidneys, liver, lungs, and pancreas (Goh et al., 2013).

The major scientific and technological progresses described here and many others that space does not allow to mention hold great promises for the coming of age of regenerative medicine.

References

Eiraku M, Takata N, Ishibashi H, Kawada M, Sakakura E, Okuda S, Sekiguchi K, Adachi T, Sasai Y. 2011. Self-organizing optic-cup morphogenesis in three-dimensional culture. Nature 472:51-56.

Goh SK, Bertera S, Olsen P, Candiello JE, Halfter W, Uechi G, Balasubramani M, Johnson SA, Sicari BM, Kollar E, Badylak SF, Banerjee I. 2013. Perfusion-decellularized pancreas as a natural 3D scaffold for pancreatic tissue and whole organ engineering. Biomaterials 34:6760-6772.

Lancaster MA, Renner M, Martin CA, Wenzel D, Bicknell LS, Hurles ME, Homfray T, Penninger JM, Jackson AP, Knoblich JA. 2013. Cerebral organoids model human brain development and microcephaly. Nature 501:373-379.

Mason C, Dunnill P. 2008. A brief definition of regenerative medicine. Regen Med 3:1-5.

Obokata H, Wakayama T, Sasai Y, Kojima K, Vacanti MP, Niwa H, Yamato M, Vacanti CA. 2014. Stimulus-triggered fate conversion of somatic cells into pluripotency. Nature 505:641-647.

Sato T, Vries RG, Snippert HJ, van de Wetering M, Barker N, Stange DE, van Es JH, Abo A, Kujala P, Peters PJ, Clevers H. 2009. Single Lgr5 stem cells build crypt-villus structures in vitro without a mesenchymal niche. Nature 459:262-265.

Takahashi K, Yamanaka S. 2006. Induction of pluripotent stem cells from mouse embryonic and adult fibroblast cultures by defined factors. Cell 126:663-676.