Regenerative medicine is a complex and rapidly advancing field that holds tremendous promise in treating, and even curing, many diseases. The understanding and control of tissue repair is one of the most urgent challenges in medicine today. Regenerative medicine seeks to either recruit the patient’s reparative cells or to replace the malfunctioning tissue altogether to restore the deficient organ to adequate function. The common link among all types of regenerative therapies is the stem cell, which gives all tissues the capacity to regenerate. The mechanisms underlying the ability of a progenitor cell to differentiate have been challenging to elucidate, with recent experimentation focused on editing the genome itself. It has been even more difficult to determine how a differentiated cell can be instructed to revert to an immature state and undergo a re-specification to another differentiated cellular phenotype or an asymmetrical division to generate more immature cells. Our ability to modify genomes, harness stem cells, and transplant autologous or allogeneic tissues has transformed biomedical inquiry and offers hope to patients with diseases spanning all organ systems, including cardiac, lung, central nervous system, and liver and pancreatic diseases.
Acronyms and Abbreviations:
ALS, amyotrophic lateral sclerosis; AMI, acute myocardial infarction; ATI or ATII, alveolar epithelial cells type I or II; BASCs, bronchiolar alveolar stem cells; BDNF, bone-derived neurotrophic factor; BM-derived, marrow-derived; CAR, chimeric antigen receptor; CDCs, cardiac-derived stem cells; COPD, chronic obstructive pulmonary disease; CRISPRs, clustered regularly interspaced short palindromic repeats; dmPGE2,16,16-dimethyl-prostaglandin E2; DPSCs, dental pulp stem cells; DSB, double-strand break; EC, embryonic carcinoma; ESCs, embryonic stem cells; EPCs, epithelial progenitor cells; FAH, fumarylacetoacetate hydrolase; GVHD, graft-versus-host disease; HCT, hematopoietic cell transplantation; hESC, human embryonic stem cell; HR, homologous recombination; IDLV, integrase-deficient lentiviral; iPSCs, induced pluripotent stem cells; MN, meganuclease; MNCs, mononuclear cells; MSCs, mesenchymal stromal/stem cells; NHEJ, nonhomologous end-joining; NSC, neural stem cell; OPCs, oligodendrocyte progenitor cells; OT, off target; PD, Parkinson disease; SCID-X1, X-linked severe combined immunodeficiency; SCNT, somatic cell nuclear transfer; TALEN, transcription activator-like effector nuclease; TCR, T-cell receptor; TGF-β1, transforming growth factor-β1; UBCs, umbilical cord blood cells; VEGF, vascular endothelial growth factor; ZFN, zinc finger nuclease.
Regenerative medicine is a concept that evolved from knowledge in genome regulation and modification, from understanding of embryonic development and “stemness” of cells, and from 50 years of experience in human transplant biology. Therefore, a narrow view of any of these disciplines is not sufficient for illuminating the mechanisms of action underlying the already accomplished successes and for guiding the potential of novel basic biology discoveries into clinically meaningful regenerative medicine (Fig. 30–1).
The three-body problem of regenerative medicine. The three factors—cell, genome, and patient—influence each other in complex and sometimes unexpected ways. These three separate scientific foci of regenerative medicine must be developed in the context of one another to have meaningful impact.
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