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37 - Stem Cell -based Musculoskeletal Tissue Engineering

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Speaker : Gun-Il Im, Ph.D. (Dept of Orthopaedics, Dongguk University Ilsan Hospital) 

Date : 2012-10-26

Location : Room 106Pharmacy Hall, Dankook University

Abstract : Adult stem cells have drawn attention as an attractive cell source for tissue regeneration. Mesenchymal stem cells (MSCs) in adults are capable of self-regeneration and differentiation into several cell types. While bone marrow provides the most universal source of MSCs, other tissues such as the periosteum, muscle, synovial membrane and adipose tissue also possess MSCs. Of these, adipose tissue offers a unique source of stem cells with considerable advantages for its accessibility and abundance. The adipose stem cells (ASCs) obtained from lipoaspirates have been also proven to possess the multilineage potential.

The focus of musculoskeletal tissue engineering is the regeneration of bone and cartilage. 

To achieve the goal, an effective induction of differentiation poses a key challenge in the use of adult stem cells. While osteogenic differentiation of bone marrow MSCs is easily induced, ASCs have much lower osteogenic potentials than bone marrow MSCs. It can be enhanced with the used of vitamin D or BMPs. Gene transfer of osteogenic growth factors such as BMPs or transcription factors such as Runx-2 and Osterix can markedly enhance the osteogenic potential of ASCs. Recent advancement in nonviral gene transfer by electroporation has achieved a high transfection rate, and shed a light to their possible clinical application. Chondrogenic differentiation of MSCs poses greater challenge than osteogenic differentiation. TGF- has been used to induce chondrogenesis from MSCs, but the markers of hypertrophy increase along with chondrogenic markers in this setting. Inhibitor of hypertrophy such as PTHrP can be used to induce chondrogenesis while suppressing hypertrophy from MSCs. It is even difficult to induce chondrogenesis from ASCs, requiring greater doses or different combination of growth factors. The nonviral gene transfer of SOX trio, the key transcription factors of chondrogenic differentiation, can also enhance the chondrogenesis from MSCs and ASCs. 

In conclusion, great efforts have been devoted to the research to engineer bone or cartilage from adult stem cells and various strategies for tissue engineering from stem cells have been developed. Nevertheless, a lot of unsolved questions and dilemmas remain until we obtain tissues of high quality from stem cells. 

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