Bone regeneration in the stem cell era: safe play for the patient?

The past decade has seen outstanding scientific progress in the field of stem cell (SC) research and clinical application. SCs are convenient both technically and biologically: they are easy to find and to culture and they can differentiate in virtually all tissues and even in whole organs. Induced pluripotent stem cells (iPSs) are a type of pluripotent SC generated in vitro directly from mature cells through the introduction of key transcription factors. The use of iPSs, however tantalizing, poses serious safety concerns because of their genomic instability. Recently, it has been suggested that the main mechanism of SC action relies on paracrine signals. Therefore, the secretome would be primarily responsible for SC effects. The therapeutical use of secretome is safer and more reliable and offers manufacturing, handling and transportation advantages. The authors discuss current applications of SCs with particular respect to bone regeneration stressing the possible risks that may arise from incautious employments of SCs—particularly when associated with stimulating factors. Safety issues hamper the advancement of SC-based innovative therapies and raise the need for novel standards to adequately address and rule out inconsistency and other concerns, considering the permanent nature of SC treatments. Many biological aspects concerning dose, time and site of administration are still to be elucidated. Solid clinical data and trials with long-term follow-ups are highly recommended as a means to evaluate the risk/benefit ratio of each potential intervention and to provide patients with clear and accurate information.