Regenerative Medicine, Stem Cells and the Liver PDF

Preface

The liver is an amazing organ which performs a myriad of functions necessary for life. The liver is highly resilient and the only internal human organ capable of large scale regeneration. During this process as little as 20–30% of healthy liver mass is all that is required to regenerate the whole liver. The regenerative capacity of the liver is captivating and some say this has been recognised for centuries, most notably in Greek mythology. The Titan Prometheus was chained to a rock and each day his liver was devoured by an eagle, only to grow back each night highlighting the liver's remarkable capacity for self-repair.

The primary regenerative response of the liver is provided by it's principal cell type, the hepatocyte. However when the liver is overwhelmed by insulting stimuli or chronically damaged, the hepatocyte response lost and a resident stem cell population is activated to regenerate functional tissue. Both acute and chronic liver injury can result in dramatic loss of human liver function and the onset of liver disease. The only real treatment for critically failing liver function is organ transplant. While transplantation is highly successful, the shortage of donor organs limits widespread implementation. Therefore researchers have been working together to explore scalable alternatives to support failing liver function. In particular, cell based therapies using human primary material have provided encouraging results. However, similar to organ transplant, there source of material is limited. This has led investigators to search for renewable cell sources, such as stem cells.

Stem cells are found in all multi-cellular organisms and divide producing identical copies of themselves, termed self renewal, or differentiate into specialized cell types. Stem cells are a very important source of cells which work to maintain organ function during human development, aging and injury. In addition to their role in tissue homeostasis, stem cells also offer great hope for developing novel medicines and cell based therapies to treat or replace diseased human tissue. Given the promise of stem cell biology and the potential it offers to human medicine in the 21st Century we have written this book.

We begin by outlining the complex nature of human liver disease and examining the potentials that stem cell based approaches have to offer.

We follow this by highlighting potential sources of cell populations for therapy and discuss the challenge with working with primary human material. All too frequently news headlines focus on the benefi ts of transplanting stem cell based products in patients. However in reality one of the most far-reaching benefi ts of stem cell research to society will be the accelerated development of novel, safer and more effective human medicines. Therefore the focus of the four following chapters discusses the role that stem cell technology has to play in understanding human biology, human disease and its application as a model to improve pharmaceutical drug development and safety. Following on from this we examine the important role that cell banking and manufacturing has to play in the scale up, quality assurance and clinical grade manufacture of stem cell derived products. This is followed by three chapters which focus on the use of cell based therapies for the treatment of human liver disease. We conclude the book with a chapter devoted to the challenges, technically and ethically, that exist for stem cell derived products for research and therapy.

I have been very lucky to work with a number of the world's experts on this project and we have endeavoured to provide comprehensive coverage of the fi eld. I hope you enjoy reading the book.