**1. Introduction**

Bone is a highly vascularized tissue with an intrinsic property to self-repair, regenerate and remodel. It has an excellent ability to heal traumatic injuries (e.g. fractures) without any formation of scars. However, there still exist a number of clinical scenarios where their selfrepair and regenerative capabilities fail. Some of the classic examples include large bone defects caused by traumatic injury, infection, tumour resection and skeletal abnormalities due to congenital diseases. Bone-related injuries resulting from these clinical scenarios have

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significant impacts on the health and lifestyle of individuals. In the USA alone, more than half a million patients experience problems due to bone defects each year, with medical cost associated with these defects being more than \$2.5 billion/annum and this figure is expected to double by 2020. It is estimated that about 2.2 million bone graft procedures are performed around the world annually [1–3]. The current strategies used for augmenting bone regenera‐ tion include different bone-grafting methods, such as autologous bone grafts and allografts [4]. Autologous bone grafts have relatively successful clinical outcomes; however, donor site morbidity, limited supply and the complicated surgical procedures associated with bone harvests hinder the efficacy of such procedures. On the other hand, allogenic bone grafts are excellent in terms of sourcing large quantities of donor tissue required for treating large bone defects; however, the issues related to immunogenicity, rejection reaction and disease transmission render this treatment less ideal [4, 5]. The shortcomings associated with these treatments have led to exploring tissue engineering approaches and stem cell-based thera‐ pies for bone repair.

There is great promise for stem cell-based therapeutics for the treatment of numerous diseases and injuries; as such, substantial investment has been made over the past decade for new therapies. Stem cells play a critical role in tissue regeneration and repair, maintenance, turnover and the control of haematopoiesis in the bone marrow. They are considered as an attractive cell population for bone repair due to their proliferation, osteogenic potential and secretion of potent endogenous trophic factors to enhance local vascularization. These cells have an incredible ability to differentiate into specific cell types like osteoblasts, chondro‐ cytes or myocytes and to develop bone, cartilage or muscle tissues. It is believed that the stem cells can help in repairing the damaged tissue not only by direct differentiation process but also indirectly through the secretion of their bioactive (trophic) factor [6]. In case of any tissue damage, the stem cells can be attracted to the damage site wherein they secrete bioactive factors that can function to trophically assist the repair and regeneration process.

In this chapter, we discuss about the (1) role of the stem cells in bone regeneration and their trophic factors and (2) the influence of stem cell microenvironment on the secretion of trophic factors and their effects on bone regeneration. The stem cell-based therapies using trophic factors may have profound clinical applications.
