Hepatocyte transplantation: past efforts, current technology, and future expansion of therapeutic potential.

Hepatic cell transplantation (HCT) continues to garner interest as an alternative to orthotopic liver transplantation and the attendant donor shortage. When compared with solid organ transplantation, advantages of cell transplantation include the potential to treat more patients with a considerably less invasive procedure, the ability to utilize organs otherwise unsuitable for transplant, and leaving the native organ in situ with the potential for regeneration. While studies date back to the early 1960s, advancement of clinical application has been slow due in part to limitations of suitable tissue supplies and reproducible robust techniques. Compared with orthotopic liver transplantation, there are fewer absolute contraindications for donor selection. And, current techniques used to harvest, isolate, store, and even transfuse cells vary little between institutions. Significant variation is seen due to a lack of consensus with maintenance therapy. Although the ideal recipient has not been clearly identified, the most significant results have been demonstrated with correction of congenital metabolic liver disorders, with a few trials examining its utility in cirrhotics and more recently acute liver failure. The most exciting new topic of discussion examines techniques to improve engraftment, with many such as ischemic preconditioning and nonselective partial embolization (microbead therapy), while not yet used in HCT study, showing promise in solid organ research. Advancements in HCT, although slow in progress, have great potential in the ability to alleviate the burden faced in solid organ transplantation and possibly become a long-term viable option, beyond that of a bridge or salvage therapy.

Pancreatic islet cell transplantation: an update for interventional radiologists.

Pancreatic islet cell transplantation is a promising cellular-based therapy for type 1 diabetes mellitus. This procedure involves portal venous injection of islet cells and affords 1-year insulin independence in as many as 80% of recipients. Although transplant surgeons represent historical drivers of islet therapy, requirement for image guidance and transcatheter techniques has fostered collaboration with interventional radiologists, who are positioned to play a significant role in clinical performance of islet transplantation and in basic science research in this field. This review article aims to familiarize interventional radiologists with islet cell transplantation patient selection, procedure technique, clinical outcomes, and future clinical and research avenues.

Chapter 55: neural transplantation.

The history of cell transplantation in the nervous system is reviewed in four main sections. The "early era" spans the period from 1890 to 1940, during which the first attempts at cell transplantation in the brain were undertaken. Many contemporary themes were first addressed such as surgical factors to achieve survival of grafted cells and how that should be assessed, immunological factors, use of tumors as a readily viable cell source; and use of the anterior eye chamber as a model transplantation site. However, such studies generally exhibited only low levels of viability or successful implantation. The "middle era" from 1940 to 1970 spans the period when the techniques for viable and reliable cell transplantation using embryonic donor tissues implanted into sites with effective vascularization were first established in brain and neuroendocrine systems in a limited number of specialist centers. However, although sometimes impressive, these results were at variance with the prevailing view that the adult mammalian brain is immutable and resistant to plasticity, growth or regeneration, and were largely ignored. The "modern era," since 1970, began with the pioneering studies that combined cell transplantation with the use of improved histochemical and ultrastructural anatomical techniques to demonstrate selectivity, specificity and regenerative capacity of implanted cells, and the slow acceptance that the adult brain does exhibit considerable potential for plasticity and repair. The last three decades have witnessed the identification of reliable and efficient transplantation technologies combined with progressively refined methods of molecular, cellular, biochemical, physiological and functional analysis. This now enables the ready use of cell transplantation as a powerful novel method within the neuroscience tool-kit, which is being used: to analyze normal organization and function of the nervous system; to reveal the biological mechanisms and principles of neuronal development, regeneration and plasticity; and to study the principles of surgically directed cell therapies for promoting plasticity, replacement and repair in response to injury and disease. The final section reviews recent progress in translating cell transplantation to the clinic for application in Parkinson's and other central nervous system diseases.

[Development and status quo of testis transplantation].

A lot of advances have been made in testis autotransplantation, testis homotransplantation, testicular tissue transplantation, Leydig cell transplantation and spermatogonial stem cell transplantation in the past decades. And recent years, have witnessed remarkable progress in Leydig cell transplantation and spermatogonial stem cell transplantation, which promise to be new means for the treatment of male infertility and hypogonadism. The development and present state of testis transplantation are summarized in this paper based on the related literature of recent years.

The birth of therapy with cultured cells.

Long ago, I set out to solve a problem, but something happened along the way: I was diverted by an unexpected observation. Thereafter, the direction of my research was guided at each stage by increasing familiarity with the experimental material and what could be done with it. The result was the birth of therapy with cultured keratinocytes. Subsequent developments soon led to the formation of the company Biosurface Technology (later taken over by the Genzyme Corporation), which provided autologous cultures for burn victims in many parts of the world. Further progress by others led to new therapeutic applications of cultured keratinocytes, such as treatment of an ocular disease and gene therapy. Unfortunately, there have developed serious regulatory problems that are a danger to future progress. As described in this brief history, the initial stages of development of cell therapy for the treatment of human disease were possible only because there was no restraint by committees or governmental regulations.

History of xenotransplantation.

The present historical review reports the clinical experiences of transplantations from animal to human. The first transplantation attempts were made without any knowledge of the species barrier. The pioneers of xenotransplantation realized xenotransfusions as early as the 16th century, then cell and tissue xenotransplantations in the 19th century. At the beginning of the 20th century, xenotransplantation of testicles became the latest craze. At the same time, and later in the 1960s, organ xenotransplantations were attempted, with disappointing results. Mathieu Jaboulay, Serge Voronoff, Keith Reemtsma, James Hardy, Denton Cooley, Thomas Starzl, Christiaan Barnard and Leonard Bailey were among the pionneers of xenotransplantation. Recent trials concerned above all tissue and cell xenotransplantations. Nowadays, with encapsulation, transgenesis, and cloning, great advances have been made for controlling xenograft rejection, but ethical questions linked to the risk of infections have become a major pre-occupation within the scientific community and the general population.