Bench-to-bedside development of MSC therapies: A multidisciplinary approach

Abstract

There is a worldwide interest in developing mesenchymal stromal/stem cells (MSCs) for a broad and steadily expanding range of potential clinical applications. Whether developed by academia or industry, successful transition from the research bench to the clinic requires a systematic, coordinated, and multidisciplinary approach to execute the many simultaneous, interrelated activities aimed at demonstrating the product's safety and efficacy. Like conventional drug development, MSC product development requires attention to basic and translational science, preclinical safety and efficacy studies in animal models, manufacturing process development, good manufacturing practice, development and validation of analytical methods to characterize the product, quality control and quality assurance, regulatory affairs, and design and execution of clinical trials. Broad expertise is needed to accomplish these activities and includes molecular and cell biologists; scientists and technicians to develop and perform laboratory assays, manufacturing, and imaging; physicians with expertise in the disease application and clinical trials; pathologists; clinical imaging experts; nurses and clinical trials staff; veterinarians; quality officers; regulatory affairs experts, technology transfer officers and patent counsels; and institutional ethics committees. An integrated project management approach can be adapted by both academia and industry to successfully negotiate the complex product development pathway. In this chapter, we review the preclinical, manufacturing, clinical, quality, and regulatory requirements to move MSC products from bench to bedside and highlight the resources needed for success in this endeavor.