Chester J. Koh and Anthony Atala
Institute for Regenerative Medicine
Wake Forest University School of Medicine


Tissue engineering strategies generally fall into two categories:acellular matrices, where matrices are used alone and dependon the body’s natural ability to regenerate for properorientation and direction of new tissue growth, and matriceswith cells.  Acellular tissue matrices are usually prepared byremoving cellular components from tissues via mechanical andchemical manipulation to produce collagen-rich matrices.  These matrices tend to slowly degrade on implantation and aregenerally replaced by the extracellular matrix {ECM} proteins that are secreted bythe ingrowing cells.


When cells are used for tissue engineering, a small piece ofdonor tissue is dissociated into individual cells.  These cellsare either implanted directly into the host or are expandedin culture, attached to a support matrix, and then re-implantedinto the host after expansion.  The source of donor tissue canbe heterologous (different species), allogeneic (same species,different individual), or autologous (same host).  Ideally, both structuraland functional tissue replacements will occur with minimal complications.The most preferred cells to use are autologous.  The use of thesecells avoids rejection, and thus the deleterious side effectsof immunosuppressive medications can be avoided.


One of the limitations of applying cell-based regenerative medicinetechniques toward organ replacement has been the inherent difficultyof growing specific cell types in large quantities.  Even whensome organs, such as the liver, have a high regenerative capacityin vivo, cell growth and expansion in vitro may be difficult.  By studying the privileged sites for committed precursor cellsin specific organs, as well as exploring the conditions thatpromote differentiation, one may be able to overcome the obstaclesthat could lead to cell expansion in vitro.  Major advances have been achieved withinthe last decade on the possible expansion of a variety of primaryhuman cells, with specific techniques that make the use of autologouscells possible for clinical application.


For cell-based tissue engineering, the expanded cells are seededonto a scaffold synthesized with the appropriate biomaterial.  In tissue engineering, biomaterials replicate the biologic andmechanical function of the native ECM found in tissues in thebody by serving as an artificial ECM.  As a result, biomaterialsprovide a three-dimensional space for the cells to form intonew tissues with appropriate structure and function, and alsocan allow for the delivery of cells and appropriate bioactivefactors (e.g., cell adhesion peptides, growth factors), to desiredsites in the body.  Because the majority of mammalian celltypes are anchorage dependent and will die if no cell-adhesionsubstrate is available, biomaterials provide a cell-adhesionsubstrate that can deliver cells to specific sites in the bodywith high loading efficiency.  Biomaterials can also providemechanical support against in vivo forces such that the predefinedthree-dimensional structure is maintained during tissue development.  Furthermore, bioactive signals, such as cell-adhesion peptidesand growth factors, can be loaded along with cells to help regulatecellular function.


Although there has been tremendous interest in the field ofNuclear Cloning since the birth of Dolly in 1997, the firstsuccessful nuclear transfer was reported over 50 years ago.  There are two types of nuclear cloning, reproductive cloning and therapeuticcloning, and a better understanding ofthe differences between the two types may help to alleviatesome of the controversy that surrounds these revolutionary technologies.  While reproductivecloning is used to generate an embryo that has the identicalgenetic material as its cell source, therapeuticcloning is used to generate early stage embryos that are explantedin culture to produce embryonic stem cell lines whose geneticmaterial is identical to that of its source.  These autologousstem cells have the potential to become almost any type of cellin the adult body, and thus would be useful in the treatment of diseases, for which there islimited availability of immuno-compatible tissue transplants.


Therefore, therapeutic cloning, which has also been called somaticcell nuclear transfer, provides an alternative source of transplantablecells that theoretically may be limitless. As a result, with therapeutic cloning, the variety of seriousand potentially life-threatening complications associated withimmunosuppressive treatments may be avoided.

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