The Convergence of Fracture Repair and Stem Cells: Interplay of Genes, Aging, Environmental Factors and Disease

Abstract

The complexity of fracture repair makes it an ideal process for studying the interplay between the molecular, cellular, tissue, and organ level events involved in tissue regeneration. Additionally, as fracture repair recapitulates many of the processes that occur during embryonic development, investigations of fracture repair provide insights regarding skeletal embryogenesis. Specifically, inflammation, signaling, gene expression, cellular proliferation and differentiation, osteogenesis, chondrogenesis, angiogenesis, and remodeling represent the complex array of interdependent biological events that occur during fracture repair. Here we review studies of bone regeneration in genetically modified mouse models, during aging, following environmental exposure, and in the setting of disease that provide insights regarding the role of multipotent cells and their regulation during fracture repair. Complementary animal models and ongoing scientific discoveries define an increasing number of molecular and cellular targets to reduce the morbidity and complications associated with fracture repair. Last, some new and exciting areas of stem cell research such as the contribution of mitochondria function, limb regeneration signaling, and microRNA (miRNA) posttranscriptional regulation are all likely to further contribute to our understanding of fracture repair as an active branch of regenerative medicine.

Emergent properties of neural repair: elemental biology to therapeutic concepts

“…Such similarity in tissue repair in stroke to neurodevelopment has prompted suggestions that brain regeneration recapitulates development 117. Similar comparisons to regeneration and development have been made in other systems, such as kidney, bone, liver, and skin 118, 119, 120, 121…”

Age-related decline in the matrix contents and functional properties of human periodontal ligament stem cell sheets

“…Theoretically, there are two aspects of aging that may affect stem-cell-based tissue regeneration. Changes in the microenvironment (e.g., growth factors and hormones) that alter the biological activity of stem cells play an equally important role as intrinsic (genetic and epigenetic) changes such as changes in quantity, changes in quality (differentiation/regeneration capacity), and changes in mobilization capacity in stem cell populations [32,[60][61][62]. Defining the mechanisms involved in stem cell aging is important because reversal of this process can delay the effects of aging and enhance regeneration [63,64].…”

Pulp Revascularization on Permanent Teeth with Open Apices in a Middle-aged Patient

“…The comparatively delayed bone healing in our patient is likely related to her age. Two aspects of aging could affect tissue rehabilitation: intrinsic changes in stem cells and changes in the local environment that regulate the biological properties of stem cells (19). Adult progenitor cells, existing essentially in all tissues, modulate tissue homeostasis and regeneration.…”