Regenerative medicine encompasses a broad array of therapies, from hematopoietic stem cell therapies currently in clinical practice to therapies derived from human embryonic stem cells and human induced pluripotent stem (iPS) cells. Ten cell therapies are currently on the US market, ranging from treatments for hematopoietic reconstitution (e.g., Hemacord and Ducord), to mucogingival wounds (Gintuit) to cartilage repair (Carticel), all the way to cosmetics for the correction of severe wrinkles (LaVive).

More than most other fields of biomedicine, cell therapies face a complex path to market. Even the scale-up of less controversial adult stem cell therapies requires innovative thinking and new delivery systems (Commentary, p. 729). Developing therapies derived from pluripotent stem cells presents even stiffer challenges, although several groups are pushing treatments into the clinic for such conditions as age-related macular degeneration, refractory thrombocytopenia, epidermolysis bullosa (Nat. Biotechnol. 31, 483–486, 2014) and diabetes. Translation of regenerative medicine treatments involves not only regulatory issues (see Podcast; Correspondence p. 721) but also ethical, political (Correspondence, p. 724) and legal (Patent Article, p. 742; Patent Table, p. 749) issues. In the face of these crosswinds, several states have set up specific programs to facilitate commercialization of cell therapy products (Feature p. 736).

In the research arena, progress is accelerating through advances at the intersection of cell biology and technology. A key aspect of any allogeneic cell therapy is the issue of immune rejection of transplanted cells. Decades of clinical experience in transplanting solid organs and hematopoietic cells offer important lessons on immunosuppression, and new tolerance-induction strategies are being developed specifically for applications in cell therapy (Review, p. 786). The ability to improve cell therapies depends on understanding the fate of cells after transplantation into patients. Frank, Murry and colleagues review the capabilities and limitations of clinical imaging technologies for assessing cell fate and the extent of regeneration (Review, p. 804). Conventional transplantation of whole organs is easier on sensitive cells than cell therapy because the cells' native microenvironment is preserved. 3D bioprinting, a high-tech version of traditional tissue engineering, aims to produce transplantable tissues and organs in the laboratory to address the severe shortage of donor organs (Review, p. 773; News Feature, p. 716).

For some diseases, it may be possible to avoid cell therapy altogether using small molecules, proteins or biomaterials to activate latent molecular pathways of regeneration or to introduce new ones. Watt and colleagues consider the prospects for enhancing regeneration by manipulating the stem-cell niche (Review, p. 795).

Innovations in in vitro modeling of development and disease are facilitating the study of tissue regeneration and the search for drugs to control these processes. Microfluidic 'organs-on-chips' allow more precise control over cell patterning and microenvironmental conditions than conventional cell-culture systems and show promise for recapitulating organ-level functions. Potential applications in regenerative medicine include drug testing and investigation of organ development, physiology and pathology (Perspective, p. 760). In a separate piece, Ken Garber explores the use of patient-derived iPS cell lines as a tool for creating neuron- and glia-like cells to probe disease mechanisms and screen drug candidates (News Feature, p. 712). An editorial discusses the importance of a broad range of different treatment modalities in realizing the potential of regenerative medicine (Editorial, p. 699).