Stem cell–based therapies in pediatric disorders: translational advances, unresolved challenges, and future horizons

Abstract

Pediatric disorders consist of genetic, hematologic, neurologic, autoimmune, and inflammatory diseases. These conditions impose long-term health challenges on children, despite many advancements with conventional medicine. Although conventional treatments increase life expectancy and provide better disease control, many present challenges such as toxicity, insufficient control of the disease, and adverse effects on normal growth, development, and quality of life. Many researchers have shown increased interest in using stem cell therapies as an alternative to current medications to allow for complete, sustainable repair of damaged tissues and modification of disease processes (i.e., using stem cells to regenerate tissue or change the way in which a disease occurs). This paper will provide the current information on stem cells used in the treatment of children and the many different types of stem cells, including: hematopoietic stem cells (and their derivatives), mesenchymal stem cells (and their derivatives), induced pluripotent stem cells, embryonic stem cells, tissue-specific progenitor cells, extracellular vesicles, and bioengineered products. This paper will also discuss what is known about the stem cells listed as well as their methods of action, where they might currently be better utilized, and future uses of these cells in children for a variety of types of pediatric diseases. Because each stem cell type listed has very different scientific background and clinical evidence, there is much variability in the amount of scientific evidence available to support stem cell therapies. For example, hematopoietic stem cell transplantation (HSCT) has over 50 years of clinical experience; thus, there are many studies defining the clinical efficacy and long-term outcomes associated with HSCT. Conversely, while there are many published studies supporting the use of mesenchymal stem cells (MSCs), extracellular vesicles (EVs), gene-edited cells, organoids, and many induced pluripotent stem cell-derived therapies, more evidence (clinical and basic science) is still needed to fully establish efficacy for the use of these various stem cells in children with pediatric diseases. In addition to needing more clinical evidence, stem cell-based therapies face many important challenges to the advancement of these therapies, including (but not limited to) long-term safety assessments, manufacturing standardization, regulatory oversight, ethical concerns, and equitable access to advanced therapies. Addressing these challenges will be important for future advances in the use of regenerative medicine in pediatric patients which will also require the rigorous evaluation of new stem cell therapies, the continued improvement of translational mechanisms, and the ongoing incorporation of new techniques (e.g., genome editing, organoid modeling, EV therapeutics, bioengineering, and artificial intelligence) to advance regenerative medicine and demonstrate its value through safe and reproducible clinical trial results.