Bioengineering Hearts: Simple yet Complex

Abstract

Purpose of review: In this review, we focus on the multiple advancements in the field of cardiovascular regenerative medicine and the state-of-the art of building a heart. An organ is comprised of cells, but cells alone do not comprise an organ. We summarize the components needed, the hurdles, and likely translational steps defining the opportunities for discovery.

Recent findings: The therapies being developed in regenerative medicine aim not only to repair, but also to regenerate or replace ailing tissues and organs. The first generation of cardiac regenerative medicine was gene therapy. The past decade has focused primarily on cell therapy, particularly for repair after ischemic injury with mixed results. Although cell therapy is promising, it will likely never reverse end-stage heart failure; and thus, the unmet need is, and will remain, for organs. Scientists have now tissue engineering and regenerative medicine concepts to invent alternative therapies for a wide spectrum of diseases encompassing cardiovascular, respiratory, gastrointestinal, hepatic, renal, musculoskeletal, ocular, and neurodegenerative disorders. Current studies focus on potential scaffolds and applying concepts and techniques learned with testbeds to building human sized organs. Special focus has been given to scaffold sources, cells types and sources, and cell integration with scaffolds. The complexity arises in combining them to yield an organ.

Summary: Regenerative medicine has emerged as one of the most promising fields of translational research and has the potential to minimize both the need for, and increase the availability of, donor organs. The field is characterized by its integration of biology, physical sciences, and engineering. The proper integration of these fields could lead to off-the-shelf bioartificial organs that are suitable for transplantation. Building a heart will necessarily require a scaffold that can provide cardiac function. We believe that the advent of decellularization methods provides complex, unique, and natural scaffold sources. Ultimately, cell biology and tissue engineering will need to synergize with scaffold biology, finding cell sources and reproducible ways to expand their numbers is an unmet need. But tissue engineering is moving toward whole organ synthesis at an unparalleled pace.

Keywords: Decellularized extracellular matrix; Heart; Regenerative medicine; Stem cells; Tissue engineering.

Fig. 1

Multiple applications of the decellularized extracellular matrix (dECM) in the path of components of and steps toward building a fully functional heart. dECM can generate patches, valves, vessels, and substrates that can be used as an adjunct therapeutic tool for other regenerative medicine approaches including cell therapy and in-vitro drug testbeds