Development of Facial Bone from Stem Cells Marks Groundbreaking Discovery in Tissue Engineering
January 17, 2009
In the recent years, the identification of the potential of human mesenchymal stem cells (hMSCs) to differentiate into myogenic, osteogenic, adipogenic, and chondrogenic lineages, has opened up diverse clinical applications in the field of regenerative medicine and tissue engineering. However, reconstructing the complexities of bone tissues in three-dimensional in vitro models has been identified as one of the greatest challenges confronted by scientists. Now, a team of US researchers report the successful creation of the temporomandibular joint (TMJ) using patient-specific stem cells and a ‘biomimetic’ scaffold-bioreactor system.
Warren L Grayson from the Department of Biomedical Engineering, Columbia University, and colleagues, used digitized clinical images for the creation of anatomically similar scaffolds from fully decellularized trabecular bone. After seeding the hMSCs to the scaffold, the cells were cultured by maintaining an interstitial flow of culture medium. A specially designed bioreactor, emulating the shape of the human TMJ, was used to regulate the perfusion through the construct. After 5 weeks of culture, analysis conducted using various techniques, revealed the following features of the artificial bone graft:
• Formation of osteoids
• Enhanced volume of mineralized matrix deposition
• Development of confluent layers of lamellar bone
Further experimental and modeling studies demonstrated that the intensity and pattern of the interstitial flow is correlated with the bone matrix density and architecture. Also, the full viability of the cells is suggested as a probable factor influencing the graft function at a given physiological density.
In another study presented at the 2009 American Association of Plastic Surgeons annual meeting, Taylor et al reported that the revitalization of large volumes of allograft holds potential implications in the reconstruction of craniomaxillofacial and axial skeleton. The review study explained the procedure adopted for the revitalization of porcine allograft mandible, using mesenchymal stem cells derived from adipose tissue and recombinant human bone morphogenic protein-2 (BMP-2). In a recently performed surgical procedure, Taylor and coworkers adopted the same strategy for artificially growing cheek bones in a patient suffering from congenital Treacher-Collins syndrome, a condition marked by underdeveloped or missing zygomatic bones.
The one day-long surgery, claimed to be the first of its kind, involved the filling of patient-specific mesenchymal cells into mineral-based scaffolding implants by drilled holes. Along with adipocyte-derived stem cells, the administration of BMP-2 induced the transformation of stem cells into osteoblasts. Further follow-up conducted after four months of the surgery demonstrated the normal development of bone structure.
On a physiological level, a combination of the three processes, osteogenesis, osteoconduction and osteoinduction, is involved in the reconstruction of bones. Bone reconstruction using autogenous grafts are reported to be more efficacious than allogenic or xenogenic grafts, bone substitutes, and alloplasts, with respect to function, form, and adaptability.
Though implantations using autogenous grafts are recognized as gold standard in reconstructive orthopedic surgery, it is associated with significant tissue morbidity at the harvest site. The recent strategies, which could be adopted for developing patient-specific viable bone grafts with complex geometries, are expected to revolutionize the current procedures of craniofacial and orthopedic reconstructions in the coming years.
References
1. Grayson WL, Fröhlich M, Yeager K, et al. Engineering anatomically shaped human bone grafts. PNAS. 2009 Oct 9. [Epub ahead of print]
2. Doctors Use Patient’s Own Stem Cells to Grow Facial Bone in Groundbreaking Procedure. Press Release. Cincinnati Children’s Hospital Medical Center. Last accessed October16, 2009.
3. Taylor JA, Jones DC, Maercks RA, Gordon CB, Billmire DA, Runyan CM. Porcine Allograft Mandible Revitalization Using Osteogenically-Induced Autologous Adipocyte-Derived Stem Cells and Periosteum. Paper presented at: American Association of Plastic Surgeons – Annual Meeting;March 23, 2009;California.
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