Skip to Main Content

The discipline of regenerative medicine is developing rapidly, is based on evolving principles of stem cell biology, and is characterized by rapid clinical investigation with rationales that lag behind the numerous laboratory studies that have emerged. This chapter reviews the areas of cell biology that have contributed to regenerative medicine and briefly discusses clinical applications. Despite the advances, the field is associated with numerous conflicting studies and a somewhat undisciplined approach to the use of the term stem cells. Nevertheless, laboratory studies have stimulated clinical trials, including prospective randomized trials to treat various types of tissue damage. The potential for this novel therapy is great, but much work is required to reduce the technology to routine clinical practice. The design of more appropriate preclinical models will better inform clinical trials design and move this field forward even more rapidly, in a manner analogous to the development of marrow transplantation 50 years ago.

Acronyms and Abbreviations

Acronyms and abbreviations that appear in this chapter include: G-CSF, granulocyte colony-stimulating factor; HSCs, hematopoietic stem cells; iPS, induced pluripotent stem cells; MSCs, mesenchymal stromal cells.

Regenerative medicine arose from the convergence of several disciplines over the last 20 years, including stem cell biology; tissue engineering; materials science; cell, tissue, and organ transplantation; and developmental and molecular biology.1,2 It has been defined as “an interdisciplinary field of research and clinical applications focused on the repair, replacement or regeneration of cell, tissues or organs to restore impaired function resulting from any cause, including congenital defects, disease, trauma or ageing.”2 Four important developments have influenced the field: (1) demonstration of putative differentiation of hematopoietic stem/progenitor cells along lineages leading to nonhematopoietic tissues; (2) differentiation of mesenchymal stromal cells found in the marrow and other sites to tissues of mesodermal and even nonmesodermal origin; (3) manipulation of embryonic stem cell differentiation; and (4) the ability to reprogram adult somatic cells-induced pluripotent stem (iPS) cells to embryonic-like cells, which in turn, can differentiate along specific lineages. The features of an ideal stem cell for clinical tissue regeneration have been identified3 as: (1) abundant (available in up to the billions); (2) can be harvested in a minimally invasive manner; (3) able to differentiate along multiple lineage pathways reproducibly; (4) able to be transplanted safely and effectively from allogeneic and autologous sources; and (5) able to be manufactured in a Good Manufacturing Practice–compliant manner.

In the first decade of the 21st century a number of studies suggested that hematopoietic cells, specifically hematopoietic stem cells (HSCs), could undergo “transdifferentiation” into cells of other lineages. The notion of a one-way HSC lineage differentiation pathway in which cells followed an orderly progression from less to more differentiated states came to be questioned (see Fig. 28–1).

Figure 28–1.

The conventional unidirectional stem cell lineage differentiation pathway was ...

Pop-up div Successfully Displayed

This div only appears when the trigger link is hovered over. Otherwise it is hidden from view.