Abstract
Defects of the craniofacial skeleton arise as a direct result of trauma, diseases, oncological resection, or congenital anomalies. Current treatment options are limited, highlighting the importance for developing new strategies to restore form, function, and aesthetics of missing or damaged bone in the face and the cranium. For optimal reconstruction, the goal is to replace “like with like.” With the inherent challenges of existing options, there is a clear need to develop alternative strategies to reconstruct the craniofacial skeleton. The success of mesenchymal stem cell-based approaches has been hampered by high heterogeneity of transplanted cell populations with inconsistent preclinical and clinical trial outcomes. Here, we discuss the novel characterization and isolation of mouse skeletal stem cell (SSC) populations and their response to injury, systemic disease, and how their re-activation in vivo can contribute to tissue regeneration. These studies led to the characterization of human SSCs which are able to self-renew, give rise to increasingly fate restricted progenitors, and differentiate into bone, cartilage, and bone marrow stroma, all on the clonal level in vivo without prior in vitro culture. SSCs hold great potential for implementation in craniofacial bone tissue engineering and regenerative medicine. As we begin to better understand the diversity and the nature of skeletal stem and progenitor cells, there is a tangible future whereby a subset of human adult SSCs can be readily purified from bone or activated in situ with broad potential applications in craniofacial tissue engineering.
Highlights
Defects of the craniofacial skeleton may arise following trauma, diseases, oncological resection, or may be secondary to congenital anomalies
mesenchymal stromal/stem cells (MSCs) have been reportedly isolated from the heart, liver, synovium, placenta, pancreas, cord blood [24], the cells which encompass MSCs are heterogenous and their ability to differentiate into osteogenic progenitors occurs is not uniform [25]
The success of MSC-based approaches has been hindered by heterogeneity of the transplanted cell populations which is mainly attributable to the lack of consistency in tissue source, but may be a result of discrepancies in approaches to detection of a pure cellular population and isolation of prospective stem cells [18, 27]
Summary
Defects of the craniofacial skeleton may arise following trauma, diseases, oncological resection, or may be secondary to congenital anomalies. Tissue engineering supports tissue regenerative processes by implementing cells, scaffolds, growth factors, gene manipulation, or combinations of these elements to reconstruct defects [5, 7, 8]. By engineering and delivering tissues with or without cells capable of replacing damaged bone, regenerative medicine offers the potential to treat critical-sized bone defects which pose challenging clinical dilemmas. Bones undergo myriad biologically important steps throughout their life cycle, such as morphogenesis and development, explosive growth and functional maturation, maintenance and repair of proper architecture and function, supporting the existence of adult skeletal stem cells [18, 19]. We will focus on the novel characterization of SSC populations with potential for implementation in craniofacial bone tissue engineering and regenerative medicine and describe their response to injury, systemic disease, and how their re-activation can contribute to tissue regeneration
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