Adult Stem Cells

Edited by Kursad Turksen

Adult stem cells have been a powerful clinical tool for the last 40 years, yet are often the forgotten stepsister of embryonic stem cells now aglow with media and political attention. This book reminds us of the scientific heft and exciting new developments emerging in the study of adult stem cells. Adult stem cells were once thought to be exclusively found in tissues that rapidly turned over: the bone marrow, the skin and mucous membrane in the gut. However, it has become increasingly apparent that these tissues were simply the ones where it was easiest to envisage a stem cell role. Other tissues, including those previously regarded as essentially inert in cell turnover, contain resident primitive, stem-like cells. The best example of this is the brain. Conventional wisdom for all but the current generation of scientists/physicians was that once the complement of neurons was set in development, no further cell replenishment was possible. Yet, now there are cells in culture derived from adult brains that grow vigorously and differentiate along multiple lineages. Their source in vivo turns over and contributes to regeneration with certain types of injury. Not all tissues contain adult stem cells, and some identified stem cells are more accurately characterized as progenitor cells. However, the range of tissues that contain a primitive population of cells capable of self-renewing and providing more differentiated offspring (the two signature characteristics of stem cells), is large. This book uniquely combines detailed descriptions of most of them and includes thorough summaries and useful bibliographies. Most of the authors viewed the cells through the complex three dimensional contexts in which the cells reside and provided thoughtful perspectives on how adult stem cells may be applied therapeutically. Curiously absent, however, is a chapter on the adult stem cell pool actively used clinically, the hematopoietic stem cell. That notwithstanding, the book is a very valuable resource for those interested in regenerative medicine as a comparable volume of detailed, yet varied biology is not available to my knowledge.

Like all volumes compiling the work of many authors there is overlap in describing basic concepts and the quality of scholarship varies from author to author, but these are modest shortcomings. Like all texts, the delay in press often dates the book's information. Interpretations offered by the authors on some topics such as plasticity would likely be different now given the extensive data about cell fusion and transdifferentiation that has emerged. However, the moving nature of the target subject is well conveyed by the authors, and it would be the readers' failing if they viewed the text as more than background for what is a rapidly changing field.

One missed opportunity in the book is to address the issue of the biologic processes forming the divide between adult and embryonic stem (ES) cells. We know these cells are dramatically different and we would not expect otherwise, but why are they different; what basic cellular events dictate the embryonic stem cell versus the adult stem cell ‘state’? ES cells for example are known to have essentially no G1-S restriction in cell cycling, while most adult stem cells are deeply quiescent in vivo, cycling rarely largely due to emphatic G1-S blockade. Why and what does that mean for our ultimate ability to manipulate stem cells in a targeted manner? Can we learn from the ES setting about what we might molecularly target in the adult stem cell to make it more likely to proliferate. Expanding adult stem cells in a controlled manner would be enormously valuable for tissue repair, genetic repair and bioengineering. Another area of interest is that the adult stem cell mostly undergoes asymmetric cell division with one daughter cell self-renewing the stem cell and the other destined to differentiate. ES cells on the other hand seem almost hardwired to symmetrically divide with both daughter cells either retaining a stem cell phenotype or both undergoing differentiation. Only early in development or under extreme conditions do adult stem cells appear to do this. Controlling the symmetric versus asymmetric decision point for stem cells could be very useful for improving tissue repair or expanding stem cell pools. Characterizing such distinctions would be very helpful for encouraging the dialogue between adult and stem cell biologists. Neither can nor should work in isolation. While this book has organized the information about adult stem cell in varying tissues, synthesizing the principles of adult stem cell biology and comparing them with ES cells will need to be added by the reader. A worthwhile exercise and, perhaps, exciting sequel.