Cell-based therapies to reconstruct craniofacial defects often utilize mesenchymal stem cells (MSCs) and osteogenic cells, transplanted with scaffolds to create an active microenvironment for osteogenesis. The restricted availability, limited life span and donor site morbidity are limitations of commonly used bone marrow stromal cells (BMSCs). Various sources of MSCs have been explored to overcome the limitations. Adipose tissue, umbilical cord, cord blood and amniotic fluid have shown a potential to be sources of MSCs with variations in growth and differentiation potential. With the accessibility and a capability to form bone, human adipose tissue has gained extensive interest as an alternative source of MSCs for transplantation.

A requirement for a large numbers of cells for transplantation with minimal adverse effects from extensive expansion on the differentiation potential and stability necessitate the development of well defined and efficient cell culture models to generate large numbers of homogenous population of MSCs. An ability to circumvent and suppress host immune response of MSCs heightens a possibility to create an allergenic MSC pool for transplantation.

Challenges of cell-based transplantation therapies are to enhance survival and integration of the transplanted cells in local tissue for continuous regeneration. Delivery vehicles play crucial roles in regulating bone formation capacity of MSCs. Mesenchymal stem cells might be pre-exposed to or transplanted with osteogenic proteins/growth factors to enhance cell survival and the differentiation potential. For the predictability of clinical outcome, reliability and consistency of bone formation capacity of MSCs in vivo need to be improved.