Review
Mesenchymal stem cells: building blocks for molecular medicine in the 21st century

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Abstract

Mesenchymal stem sells (MSCs) are present in a variety of tissues during human development, and in adults they are prevalent in bone marrow. From that readily available source, MSCs can be isolated, expanded in culture, and stimulated to differentiate into bone, cartilage, muscle, marrow stroma, tendon, fat and a variety of other connective tissues. Because large numbers of MSCs can be generated in culture, tissue-engineered constructs principally composed of these cells could be re-introduced into the in vivo setting. This approach is now being explored to regenerate tissues that the body cannot naturally repair or regenerate when challenged. Moreover, MSCs can be transduced with retroviral and other vectors and are, thus, potential candidates to deliver somatic gene therapies for local or systemic pathologies. Untapped applications include both diagnostic and prognostic uses of MSCs and their descendents in healthcare management. Finally, by understanding the complex, multistep and multifactorial differentiation pathway from MSC to functional tissues, it might be possible to manipulate MSCs directly in vivo to cue the formation of elaborate, composite tissues in situ.

Section snippets

The state of the art

In the late 1980s, the technique for isolating, purifying and mitotically expanding MSCs from marrow specimens of individuals of any age was optimized 25. With an expansion potential exceeding one billion-fold in culture 26, and the subsequent availability of large numbers of MSCs, studies were initiated to further characterize these cells and their response to various bioactive molecules. Although inductive agents that cause the entrance into and progression along individual lineage pathways

Tissue protection, repair and replacement

The surgical reconstruction of any tissue will require reparative cells and the appropriate scaffold to both introduce the cells into the wound site and support tissue specific biosynthetic events. Additionally, inductive and phenotype-specific growth factors and cytokines must sequentially interact with the implanted cells and their progeny to effectively consummate a tissue engineered reformation of functional tissue. Hybrid tissues, such as articular cartilage on a bed of subchondral bone,

Acknowledgements

We thank our colleagues at Case Western Reserve University, DePuy, and elsewhere for their encouragement and scientific stimulation. Supported in part by DePuy, Inc., and grants from National Institutes of Health.

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