In recent years, stem cell research provides fundamental knowledge for translating stem cell-mediated tissue regeneration into clinical therapies. The craniofacial region contains many specified tissues including bone, connective tissue, fat, blood vessels, neural tissue and muscle. Reconstruction of craniofacial components is one of the most important and intricate objectives in stem cell-mediated regenerative medicine (Warren et al, 2003; Cowan et al, 2004; Warnke et al, 2004). In addition, craniofacial deformities have enormous psychosocial impacts for individuals, with the most common causes for craniofacial defects being post-cancer ablative surgery, trauma, congenital malformations, and progressive deforming skeletal diseases (Phillips et al, 1992; Jeffcoat, 1993; Nguyen and Sullivan, 1993). Autogenous graft, allogeneic graft, and various alloplastic materials, such as demineralized bone matrices, synthetic bone pastes, and semisynthetic scaffolds, which have been utilized to reconstruct craniofacial defects have all led to improved clinical outcomes of various degrees. However, these approaches showed inherent limitations, such as insufficient autogenous resources, donor site morbidity, contour irregularities, disease transmission, major histoincompatibility, graft-versus-host disease (GVHD), immunosuppression, unpredictable outcome for bone formation, and infection of foreign material (Jackson et al, 1986; Oklund et al, 1986; Sawin et al, 1998; Warren et al, 2003). To overcome these limitations, stem cell-based tissue regeneration offers a promising approach to providing an advanced and reliable therapeutic strategy for craniofacial tissue repair.
One potential avenue for developing a stem cell-based therapy is the use of embryonic stem (ES) cells, which are derived from the inner cell mass of the blastocyst and possess pluripotent differentiation capacity (Evans and Kaufman, 1981; Martin, 1981; Shamblott et al, 1998; Thomson et al, 1998). Although ES cells are considered as important cell resources in the future for many tissue repair/regeneration applications, the clinical use of ES cells is still limited because of ethical issues, uncontrolled differentiation of ES cells, and immune rejection problems between donor and recipient. Moreover, long-term clinical trials are necessary to exclude the possibility of chromosomal instability and tumorigenesis when ES cells are utilized in vivo.
Tissue-specific postnatal stem cells have been isolated from a variety of organs and tissues, including but not limited to, bone marrow (Castro-Malaspina et al, 1980; Civin et al, 1984; Baum et al, 1992; Craig et al, 1993; Prockop, 1997; Pittenger et al, 1999; Kondo et al, 2003), neural tissue (Flax et al, 1998; Johansson et al, 1999), muscle (Chen and Goldhamer, 2003; Huard et al, 2003), skin (Lavker and Sun, 2000; Janes et al, 2002), eye (Lavker and Sun, 2003), intestine (Marshman et al, 2002), and liver (Alison et al, 1997; Shafritz and Dabeva, 2002). It was reported that craniofacial tissues also contain postnatal stem cells such as bone marrow-derived mesenchymal stem cells (BMMSCs), dental pulp stem cells, periodontal ligament stem cells, and stem cells from human exfoliated deciduous teeth (SHED) (Gronthos et al, 2000, 2002; Miura et al, 2003; Seo et al, 2004; Matsubara et al, 2005; Akintoye et al, 2006). However, bone marrow is the only system thus far that provides stem cells for successful and routine treatment of hematopoietic diseases, cancer therapy, and GVHD (Mulder et al, 1989; Broun et al, 1997; Thomas, 1999; Le Blanc et al, 2004). Bone marrow contains at least two populations of postnatal stem cells; hematopoietic stem cells (HSCs), which can reconstitute all blood cell lineages (Lemischka et al, 1986; Osawa et al, 1996), and mesenchymal stem cells (MSCs), which are derived from bone marrow stromal tissues with the capacity for multipotent differentiation into cell types of mesodermal origin such as osteoblasts, chondrocytes, adipocytes, and muscle cells (Castro-Malaspina et al, 1980; Prockop, 1997; Pittenger et al, 1999). Both HSCs and MSCs have been used to treat a variety of human diseases and tissue defects (Korbling and Estrov, 2003). Transplantation of whole bone marrow cells or mobilized peripheral blood, which includes HSCs and MSCs, has been used to treat a variety of hematopoietic diseases and malignancies, following systemic infusion into patients. To date, there is no evidence to show that bone marrow-derived stem cells have given rise to any primary cancers or had any association with severe side effects since the first successful allogeneic marrow graft performed in a patient 38 years ago (Thomas, 1999). Taken together, BMMSCs have been considered of an effective and safe resource for stem cell-based clinical therapy. In this review, we discuss the potential of BMMSC-mediated tissue regeneration for repairing craniofacial tissues.