Cell–based cardiovascular repair

Abstract

Cardiovascular cell therapy offers the first real potential to treat the underlying injuries associated with cardiac and vascular disease. By delivering appropriate exogenous cells to an injury site, the potential exists to mitigate injury or even to begin to reverse damage. Based on their inordinate pre-clinical promise as myogenic or angiogenic precursors, skeletal myoblasts and bone marrow or blood-derived mesenchymal and hematopoietic progenitor cells have all rapidly moved from bench to early clinical studies. From these parallel paths we are learning a number of useful lessons and have begun to visualize the hurdles to be overcome as we move these therapies forward. It is now obvious that cell-based cardiac and vascular repair are feasible-both early and later in the disease process. In fact, cell therapy may offer an unparalleled opportunity for improvement to millions of individuals living with cardiovascular disease. However, many questions about the technology remain. The mechanisms associated with cardiovascular repair remain unclear. Whether a best cell type, delivery method, or route of administration exists is unknown. And, whether cellbased disease prevention is feasible is still unanswerable. Now is the time to delve deeply into the questions of cell-based myocardial and vascular repair-even as we cautiously proceed clinically. Only by understanding these issues will we be able to decrease unanticipated clinical effects and to fulfill the potential promise of the most exciting opportunity yet to treat CVD. As we do so, we must prevent uncontrolled, poorly planned studies and until we understand cell therapy's potential, we must limit "too good to be true" promises. Only by addressing unanswered questions, carefully limiting our promises, and rigorously performing pre-clinical and clinical studies can we provide the surest opportunity for safely moving the field forward.

RETRACTED: Potential of bone marrow mesenchymal stem cells in management of Alzheimer's disease in female rats

“…For stem cell delivery to the brain, systemic administration may be preferable. Strategies for local stem cell delivery increase risks and side effects such as bleeding and tissue injury with direct tissue injection or occlusion and embolization associated with direct arterial administration (Ott et al, 2005;Dimmeler et al, 2008). Therefore, if stem cell therapy is to be broadly applied as a therapeutic strategy, a simple intravenous approach would be ideal, giving broad biodistribution and easy access (Coronel et al, 2006).…”

Coronary Artery Ligation and Intramyocardial Injection in a Murine Model of Infarction

“…The nature of mice in terms of size, reproductive capacity, and comparatively less expense for purchase and maintenance make this species an appealing tool for a broad range of physiologic and pathophysiologic studies. As the miniaturization of technology for imaging in vivo advances [46][47][48][49] , as well as means to perform and analyze large scale genomics and proteomics, drug screening, efficacy of cell-based and/or protein therapies as well as biomaterials [50][51][52][53][54][55][56][57][58][59][60][61][62][63][64] , combined with the increasingly wide range of genetic manipulations afforded by ubiquitous or tissue specific transgenic or mutant/knockout mice, the murine model of myocardial infarction will undoubtedly continue to be an invaluable tool in evaluating acute cardiac injury and long term remodeling. Therefore, there is unquestionable value in being able to perform these experiments reliably and reproducibly.…”

Differences in Stem Cell Processing Lead to Distinct Secretomes Secretion—Implications for Differential Results of Previous Clinical Trials of Stem Cell Therapy for Myocardial Infarction

“…Ischemic heart disease (IHD) following acute myocardial infarction (AMI) still constitutes the major cause of premature death and disability in Western countries . At the dawn of the new millennium, stem cell therapy seemed a promising new therapy with conceiving results in animal models . Although first human trials further nurtured hope, broad clinical application was prevented by contradictory results in large clinical trials: in REPAIR‐AMI, by Schachinger et al intracoronary bone marrow‐derived cells (BMCs) administration was associated with left ventricular functional improvement after AMI.…”