Abstract
PURPOSE: The majority of adult tissues are limited in self-repair and regeneration due to their poor intrinsic regenerative capacity. It is widely recognized that stem cells are present in almost all adult tissues, but the natural regeneration in adult mammals is not sufficient to recover function after injury or disease. Historically, 3 classes of stem cells have been defined: embryonic stem cells (ESCs), adult mesenchymal stem cells (MSCs), and induced pluripotent stem cells (iPSCs). Here, we have defined a fourth fully engineered class: the synthetic artificial stem cell (SASC). This review aims to discuss the applications of these stem cell classes in musculoskeletal regenerative engineering. METHOD: We screened articles in PubMed and bibliographic search using a combination of keywords. Relevant and high-cited articles were chosen for inclusion in this narrative review. RESULTS: In this review, we discuss the different classes of stem cells that are biologically derived (ESCs and MSCs) or semi-engineered/engineered (iPSCs, SASC). We also discuss the applications of these stem cell classes in musculoskeletal regenerative engineering. We further summarize the advantages and disadvantages of using each of the classes and how they impact the clinical translation of these therapies. CONCLUSION: Each class of stem cells has advantages and disadvantages in preclinical and clinical settings. We also propose the engineered SASC class as a potentially disease-modifying therapy that harnesses the paracrine action of biologically derived stem cells to mimic regenerative potential. LAY SUMMARY: The majority of adult tissues are limited in self-repair and regeneration, even though stem cells are present in almost all adult tissues. Historically, 3 classes of stem cells have been defined: embryonic stem cells (ESCs), adult mesenchymal stem cells (MSCs), and induced pluripotent stem cells (iPSCs). Here, we have defined a fourth, fully engineered class: the synthetic artificial stem cell (SASC). In this review, we discuss the applications of each of these stem cell classes in musculoskeletal regenerative engineering. We further summarize the advantages and disadvantages of using each of these classes and how they impact the clinical translation of these therapies.