Chapters authored
Unique Aspects of the Design of Phase I/II Clinical Trials of Stem Cell Therapy
This chapter will review the unique aspects and limitations of the design of phase I/II (safety and efficacy) clinical trials of stem cell therapy. Although the classical pharmacologic principles applicable to drugs are not applicable to biologic (live cell) therapeutic agents, an important stage in the development of any new therapeutic agent is the establishment of an optimal dosage and delivery route. This can be particularly challenging when the treatment is a biologic agent, such as stem cells, that may exert its therapeutic effects via complex or poorly understood mechanisms. To date, clinical studies have shown inconsistent findings regarding the relationship between cell dose and clinical outcomes. This can be at least partially attributed to variations in donor cell type, source, characteristics, dosing/concentration, delivery route, underlying mechanisms of action, and efficacy endpoints tested. The current recommendations will be reviewed herein to give new investigators a general understanding of the unique issues that need to be considered and addressed when designing a stem cell therapy phase I/II clinical trial.
Part of the book: The Management of Clinical Trials
Mesenchymal Stromal Cells as a Therapeutic Intervention
Mesenchymal stem cells, also known as mesenchymal stromal cells (MSCs), are a safe and promising biologic therapeutic for inducing tissue repair and regeneration in a broad array of chronic diseases. The mechanisms underlying the beneficial effects of MSCs include immunomodulation, reduction in inflammation and fibrosis, and stimulation of neovascularization and endogenous regeneration. Accumulating evidence from a multitude of clinical trials support the notion that both autologous and allogeneic MSCs are not only safe but also possess the capacity for repair of diverse organ systems and amelioration of multiple chronic disease processes. However, there are many questions regarding the underlying mechanisms of action, the most efficacious cell characteristics, tissue source, dose/concentration, route of delivery, and timing of administration, interactions with concurrent therapies, sustainability of effect, donor and patient characteristics, and adverse effects, including infections and malignancy, that remain to be resolved. Answering these questions will require well-designed and rigorously conducted multicenter clinical trials with well-established and defined clinical endpoints and appropriately defined patient populations, number of patients, and duration of follow-up. This chapter will review the current state of knowledge in the use of MSCs as a therapeutic strategy for organ structural and functional repair in chronic diseases.
Part of the book: Stromal Cells