Adult Bone Marrow-Derived Cells for Cardiac Repair: A systematic review and meta-analysis

Harvard University, Cambridge, Massachusetts, United States
Archives of Internal Medicine (Impact Factor: 17.33). 05/2007; 167(10):989-97. DOI: 10.1001/archinte.167.10.989
Source: PubMed


The results from small clinical studies suggest that therapy with adult bone marrow (BM)-derived cells (BMCs) reduces infarct size and improves left ventricular function and perfusion. However, the effects of BMC transplantation in patients with ischemic heart disease remains unclear.
We searched MEDLINE, EMBASE, Science Citation Index, CINAHL (Cumulative Index to Nursing and Allied Health), and the Cochrane Central Register of Controlled Trials (CENTRAL) (through July 2006) for randomized controlled trials and cohort studies of BMC transplantation to treat ischemic heart disease. We conducted a random-effects meta-analysis across eligible studies measuring the same outcomes.
Eighteen studies (N = 999 patients) were eligible. The adult BMCs included BM mononuclear cells, BM mesenchymal stem cells, and BM-derived circulating progenitor cells. Compared with controls, BMC transplantation improved left ventricular ejection fraction (pooled difference, 3.66%; 95% confidence interval [CI], 1.93% to 5.40%; P<.001); reduced infarct scar size (-5.49%; 95% CI, -9.10% to -1.88%; P = .003); and reduced left ventricular end-systolic volume (-4.80 mL; 95% CI, -8.20 to -1.41 mL; P = .006).
The available evidence suggests that BMC transplantation is associated with modest improvements in physiologic and anatomic parameters in patients with both acute myocardial infarction and chronic ischemic heart disease, above and beyond conventional therapy. Therapy with BMCs seems safe. These results support conducting large randomized trials to evaluate the impact of BMC therapy vs the standard of care on patient-important outcomes.

Download full-text


Available from: Ewa K Zuba-Surma,
54 Reads
  • Source
    • "Characterization of CPCs is driving forward a new era in CV biology and stem and progenitor cell therapies that regenerate myocardium lost in the wake of ischemic or other injurious stimuli would have enormous benefit to humanity. Clinical data acquired thus far from cell therapy trials using bone marrow (BM) and cardiac-derived cell fractions (Abdel-Latif et al., 2007; Bolli et al., 2011; Clifford et al., 2012; Makkar et al., 2012) appear to be safe, although the therapeutic effect is modest at best (Nowbar et al., 2014) and in most cases the observed benefits likely involve paracrine effects on endogenous repair mechanisms rather than exogenous stem cell deployment (Laflamme and Murry, 2011). Thus, there is much to learn about the biology and therapeutic potential of these cells. "
    [Show abstract] [Hide abstract]
    ABSTRACT: Mammalian hearts carry a number of primitive stem cell-like populations, although the magnitude of their contribution to tissue homeostasis and repair remains controversial. Recent CRE recombinase-based lineage tracing experiments suggest only a minor contribution to the formation of new cardiomyocytes from such cells, albeit one that might be augmented therapeutically. As the field explores clinical translation of cardiac stem cells, it will be important to understand the biology of these cells in great detail. In this review we document the various reported stem and progenitor cell populations in mammalian hearts and discuss the current state of knowledge on their origins and lineage capabilities.
    Stem Cell Research 10/2014; 13(3). DOI:10.1016/j.scr.2014.09.008 · 3.69 Impact Factor
  • Source
    • "Clinical trials using BMMNCs for cardiac repair have now been the subject of several meta-analyses (Abdel-Latif et al. 2007; Martin-Rendon et al. 2008; Clifford et al. 2012). Together, close to 2000 subjects have received BMMNCs as cell therapy for cardiac dysfunction (predominantly for ischemic cardiomyopathy). "
    [Show abstract] [Hide abstract]
    ABSTRACT: Following significant injury, the heart undergoes induced compensation and gradually deteriorates towards impending heart failure. Current therapy slows but does not halt the resultant adverse remodeling. Stem cell therapy, however, has the potential to regenerate or repair infarcted heart tissue and therefore is a promising therapeutic strategy undergoing intensive investigation. Due to the wide range of stem cells investigated, it is difficult to navigate this field. This review aims to summarize the main types of stem cells (both of cardiac and extra-cardiac origin) that possess promising therapeutic potential. Particular focus is placed on clinical trials supporting this therapeutic strategy.
    SpringerPlus 08/2014; 3(1):440. DOI:10.1186/2193-1801-3-440
  • Source
    • "While endogenous repair mechanisms have been described, the preponderance of evidence indicates a limited capacity for self-repair in the cardiovascular system. Early clinical trials have suggested that the therapeutic application of adult stem and progenitor cells derived from the bone marrow may improve the repair and function of ischemic tissue following acute myocardial infarction [2] [3] [4], chronic myocardial ischemia [5], and CLI [6] [7]. Cumulatively, these findings support the consideration of cell-based therapies as a treatment modality for ischemic cardiovascular disease [8]. "
    [Show abstract] [Hide abstract]
    ABSTRACT: The translation of cell-based therapies for ischemic tissue repair remains limited by several factors, including poor cell survival and limited target site retention. Advances in nanotechnology enable the development of specifically designed delivery matrices to address these limitations and thereby improve the efficacy of cell-based therapies. Given the relevance of integrin signaling for cellular homeostasis, we developed an injectable, bioactive peptide-based nanofiber matrix that presents an integrin-binding epitope derived from fibronectin, and evaluated its feasibility as a supportive artificial matrix for bone marrow-derived pro-angiogenic cells (BMPACs) used as a therapy in ischemic tissue repair. Incubation of BMPACs with these peptide nanofibers in vitro significantly attenuated apoptosis while enhancing proliferation and adhesion. Pro-angiogenic function was enhanced, as cells readily formed tubes. These effects were, in part, mediated via p38, and p44/p42 MAP kinases, which are downstream pathways of focal adhesion kinase. In a murine model of hind limb ischemia, an intramuscular injection of BMPACs within this bioactive peptide nanofiber matrix resulted in greater retention of cells, enhanced capillary density, increased limb perfusion, reduced necrosis/amputation, and preserved function of the ischemic limb compared to treatment with cells alone. This self-assembling, bioactive peptide nanofiber matrix presenting an integrin-binding domain of fibronectin improves regenerative efficacy of cell-based strategies in ischemic tissue by enhancing cell survival, retention, and reparative functions.
    Journal of Molecular and Cellular Cardiology 06/2014; 74C:231-239. DOI:10.1016/j.yjmcc.2014.05.017 · 4.66 Impact Factor
Show more