Skeletal Stem Cells - Engineered Bone: Tissue Engineering Intelligence Unit - page 19

(Table 2). Only the strains that displayed a fibroblastic morphology formed bone. In situ hy-
bridization using species-specific DNA repetitive sequences as probes demonstrated that bone
tissue formed in transplants of human and guinea pig blood-derived adherent cells had donor
origin. 46 In some transplants, a complete hematopoietic marrow, including adipocytes, accom-
panied the new bone (Fig. 1B). These findings clearly demonstrate that SSCs with multiple
differentiation potential similar to that of BMSCs (osteo-chondro-adipo-stromo-fibrogenic)
are present in peripheral blood cells, albeit with highly variable frequency. Obviously, many
intriguing questions related to the circulating SSCs remain to be answered, such as their origin,
destination, and participation in physiological and/or pathological skeletogenic events.
Conclusions
Recently, several discoveries have had high impact on the field of skeletal stem cell biology.
First, it was shown that the differentiation potential of SSCs is not necessarily limited to skel-
etal tissues, such as bone, cartilage, adipocytes, hematopoiesis-supporting stroma, and fibrous
tissue. Rather, SSCs may differentiate into a much broader spectrum of tissues, including muscle,
endothelial, and even neural cells, thus displaying a phenotypic plasticity. Secondly, it now
appears that SSCs are located outside of bone marrow, having a much wider distribution through-
out the body, including the dental pulp, the microvasculature, circulating blood cells, and
subcutaneous fat. These exciting data have considerably modified our views on tissue regenera-
tion in adult mammals, and they have also opened novel, potentially very promising therapeu-
tic approaches. In vivo transplantation assays has provided convincing evidence of the varied
differentiation capacities of SSCs. However, either orthotopic transplantation or systemic in-
jection, followed by careful examination of the fate of transplanted cells, will be required to
answer the question whether, in the context of a real organ physiology, SSCs can integrate into
the organ, differentiate along a physiologically relevant pathway, and play a tangible role in the
organ's function.
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