Regenaracion Craneofacial

Transfer of Advances in Science into Dental Education

Dental and Skeletal Stem Cells:
Potential Cellular Therapeutics for
Craniofacial Regeneration
Paul H. Krebsbach, D.D.S., Ph.D.; Pamela Gehron Robey, Ph.D.
Abstract: The study of stem cells has received considerable attention since the discovery that adult stem cells have the capacity to
form many different tissue types. Technicaladvances have helped identify potential stem cells, and their capacity for regenerating
tissues is being studied in transplantation models. Further study of the isolation, nature, and differentiation potential of stem cells
will likely have a positive impact on our understanding of human development and regenerative medicine. This review highlights
the difference between embryonic and adult stemcells and discusses the potential use of these cells for cellular therapeutics for
craniofacial regeneration.
Dr. Krebsbach is Associate Professor of Dentistry and Biomedical Engineering, University of Michigan, and Dr. Robey is Branch
Chief, Craniofacial and Skeletal Diseases Branch, National Institute of Dental and Craniofacial Research, National Institutes of
Health. Direct correspondence andrequests for reprints to Dr. Paul H. Krebsbach, University of Michigan School of Dentistry,
Department of Oral Medicine, Pathology, and Oncology, 1011 North University Avenue, Ann Arbor, MI 48109-1078; 734-9362600 phone; 734-764-2469 fax; paulk@umich.edu.
Key words: stem cells, tissue engineering, regeneration, dentistry, bone marrow stromal cells, dentin, bone
Submitted for publication3/15/02; accepted 4/25/02

T

he human body has a remarkable capacity for
regeneration. Cells in tissues such as blood
and epithelia divide rapidly and are regenerated continually throughout life, whereas cells in most
other tissues turn over more slowly and respond only
to specific biological signals.
The unique cells that give rise to specialized
tissues are termed stem cells. Stem cells areextraordinary cells that have the capacity for self-renewal
and can give rise to one and sometimes many different cell types. In mature tissue, these adult stem cells
(ASCs) play a major role in homeostasis and tissue
repair. Although such stem cells have been studied
for decades, recent findings suggest that ASCs have
astonishing and unanticipated capacities to develop
into diverse tissues.Even more remarkable is the
developmental capacity of embryonic stem cells. Embryonic stem cells (ESCs) can, in theory, give rise to
all tissue types and, as such, provide much hope for
understanding human development and for regenerative medicine.

766

Embryonic Stem Cells
In the simplest sense, a fertilized egg represents the fundamental stem cell because it is totipotent and candevelop into a complete organism. In
early development, the totipotent fertilized egg undergoes several rounds of rapid cell divisions before
the cells begin to specialize. By the blastocyst stage
of development, a specialized compartment called
the inner cell mass begins to take shape. Cells within
the inner cell mass have been termed embryonic stem
cells (ECSs) (Figure 1). Murine ESCs can begenetically modified and are used to develop transgenic
mice that have a deficient gene, overexpress it, or
express a mutated form. These animal studies demonstrate that when placed into a developing embryo,
ESCs have the capacity to form every type of cell
found in the body. Scientists have learned to culture
these ESCs and have demonstrated that they have an
extraordinary ability to formmany cell types. ESCs
therefore may represent a repository of cells for po-

Journal of Dental Education ■ Volume 66, No. 6

Figure 1. Stem cells derived from the inner cell mass of blastocyst stage human embryos have been shown to
differentiate into several different cell types and have the potential to one day replace or regenerate tissues.

tential uses in regenerative medicine.1,2 As...