Catálogo de publicaciones - libros

For continued clinical gains in the practice of radiotherapy, management of breathing motion is essential. The problem of organ motion in radiotherapy is complex; thus, interventions to reduce organ-motion-related uncertainties require effort, expertise, and collaboration from many disciplines. The application of image-guidance techniques, i.e., imageguided radiotherapy, will play an increasing important role in developing new and improved delivery techniques, i.e., adaptive radiotherapy. With some anecdotal clinical evidence and many potentially beneficial but unproven technologies under development and on the horizon, it is essential to place equal emphasis on the planning and implementation of prospective clinical trials.

Treatment of damaged myocardium after myocardial infarction by cell transplantation is becoming an increasingly promising therapeutic approach. Ideally, the donor cells should be amplified efficiently in culture and would lead to regeneration of infarcted myocardial tissue, including cardiogenic differentiation with local angiogenesis. Two of the most widely used cell types for cardiac repair today are skeletal muscle-derived progenitors, or myoblasts, and bone marrow-derived progenitors. Both cell types share advantages over other cells used for cardiac repair (or at least for limiting infarcts) in that they are readily available, autologous, exhibit a high proliferative potential and share a low potential for tumor genesis.

However, the transplantation of autologous cells to repair the heart also has serious drawbacks. It is labor intensive since isolation and cell proliferation has to be done for each patient. This procedure also delays the treatment. The ‘ideal’ cell to treat the heart should be transplantable without delay to any patient without a sustained immunosupression. Such ideal cells may be obtained one day by the genetic engineering of embryonic stem cells.

Through cellular therapies, the concept of “growing” heart muscle and vascular tissue and manipulating the myocardial cellular environment may revolutionize the approach to treating heart disease.

For continued clinical gains in the practice of radiotherapy, management of breathing motion is essential. The problem of organ motion in radiotherapy is complex; thus, interventions to reduce organ-motion-related uncertainties require effort, expertise, and collaboration from many disciplines. The application of image-guidance techniques, i.e., imageguided radiotherapy, will play an increasing important role in developing new and improved delivery techniques, i.e., adaptive radiotherapy. With some anecdotal clinical evidence and many potentially beneficial but unproven technologies under development and on the horizon, it is essential to place equal emphasis on the planning and implementation of prospective clinical trials.

This chapter outlined the authors’ current perspective on the complexities of general product testing requirements and design characteristics for preclinical studies involved in investigational use of cellular products for cardiac repair. The IND process is intended to balance the potential benefit of novel therapies to society with the need to generate data for prudent product development, to increase scientific knowledge, to protect subject safety, and to benefit the public health. This chapter represents an introduction to the regulation of these cellular products and investigator/sponsors are encouraged to contact FDA CBER OCTGT for more specific information on the conduct of clinical trials.

Skeletal myoblast transplantation opened the field of cellular cardiomyoplasty and remains its best studied procedure. Preclinical studies have moved to randomized clinical trials; lessons have been learned and questions remain. Cell transplantation offers the promise of a new era in the treatment of cardiovascular disease, but only if this new modality is carefully evaluated. Combining genomics, tissue engineering and advanced imaging methods to understand the mechanisms by which cell engraftment improves function, to promote graft longevity, and to improve electromechanical graft integration are the next preclinical frontiers. Basing clinical trials on good pre-clinical data, carefully defining the best cell type for a given clinical situation and performing randomized controlled trials that can be compared world-wide are the tasks before us as a field. Accepting the challenge, and pushing back this frontier is our opportunity. Changing patient outcomes will be our prize. Yet, doing it improperly could relegate this promising field to failure before its potential is realized.

This chapter outlined the authors’ current perspective on the complexities of general product testing requirements and design characteristics for preclinical studies involved in investigational use of cellular products for cardiac repair. The IND process is intended to balance the potential benefit of novel therapies to society with the need to generate data for prudent product development, to increase scientific knowledge, to protect subject safety, and to benefit the public health. This chapter represents an introduction to the regulation of these cellular products and investigator/sponsors are encouraged to contact FDA CBER OCTGT for more specific information on the conduct of clinical trials.

Epicardial transplantation of skeletal myoblasts in conjunction with a CABG or LVAD procedure is feasible and safe, and it does not appear that 116 Edward B. Diethrich cell transplantation poses a substantial risk of life-threatening arrhythmia in this small evaluation. Further study of the efficacy of myoblast transplantation is warranted, and we are now involved in investigations of catheterbased delivery systems and imaging protocols that support percutaneous skeletal myoblast transplantation (as described in “Percutaneous Myoblast Transplantation”, chapter 14 of this text).

This chapter outlined the authors’ current perspective on the complexities of general product testing requirements and design characteristics for preclinical studies involved in investigational use of cellular products for cardiac repair. The IND process is intended to balance the potential benefit of novel therapies to society with the need to generate data for prudent product development, to increase scientific knowledge, to protect subject safety, and to benefit the public health. This chapter represents an introduction to the regulation of these cellular products and investigator/sponsors are encouraged to contact FDA CBER OCTGT for more specific information on the conduct of clinical trials.

Adult stem cells are found in many tissues and participate in adult growth as well as repair and regeneration of damaged tissue. Adult stem cells such as MSCs may be the cell of choice for tissue repair because the cellular and tissue environment in the adult is likely very different from the early embryo conditions that produce embryonic stem cells. Bone marrow provides an accessible and renewable source of adult mesenchymal stem cells that can be greatly expanded in culture and characterized. Culture-expanded and characterized MSCs have been tested for their ability to differentiate into several lineages and also tested in animal models for their ability to enhance tissue repair and undergo differentiation. One of their greatest attributes is their potential to supply growth factors and cytokines to repairing tissue. MSCs do not appear to be rejected by the immune system, allowing for large scale production, appropriate charaterization and testing, and the subsequent ready availability of allogeneic tissue repair enhancing cellular therapeutics. This provides for the further development of this new field and paves the way for the use of yet other stem cells. The potential to use MSCs to repair damaged cardiovascular tissue is very promising and moving forward quickly. The current results from many labs and early cardiac clinical studies suggest important therapeutic approaches will be forthcoming through the use of MSCs. Perhaps most importantly, the understanding of adult stem cells such as the MSCs will provide us with greater understanding of the role they play in human biology in the developing and aging man.

Treatment of damaged myocardium after myocardial infarction by cell transplantation is becoming an increasingly promising therapeutic approach. Ideally, the donor cells should be amplified efficiently in culture and would lead to regeneration of infarcted myocardial tissue, including cardiogenic differentiation with local angiogenesis. Two of the most widely used cell types for cardiac repair today are skeletal muscle-derived progenitors, or myoblasts, and bone marrow-derived progenitors. Both cell types share advantages over other cells used for cardiac repair (or at least for limiting infarcts) in that they are readily available, autologous, exhibit a high proliferative potential and share a low potential for tumor genesis.

However, the transplantation of autologous cells to repair the heart also has serious drawbacks. It is labor intensive since isolation and cell proliferation has to be done for each patient. This procedure also delays the treatment. The ‘ideal’ cell to treat the heart should be transplantable without delay to any patient without a sustained immunosupression. Such ideal cells may be obtained one day by the genetic engineering of embryonic stem cells.

Through cellular therapies, the concept of “growing” heart muscle and vascular tissue and manipulating the myocardial cellular environment may revolutionize the approach to treating heart disease.