Adult Bone Marrow Cell Therapy Improves Survival and Induces Long-Term Improvement in Cardiac Parameters

Jeevanantham, Vinodh; Butler, Matthew J.; Saad, Andre; Abdel‐Latif, Ahmed; Zuba‐Surma, Ewa; Dawn, Buddhadeb

doi:10.1161/circulationaha.111.086074

Cited by 427 publications

(373 citation statements)

References 75 publications

Supporting

Mentioning

349

Contrasting

Unclassified

Order By: Relevance

“…Combining bioactive materials with stem cell products represents a natural extension of these approaches given recent meta-analyses demonstrating only modest persistence of injected stem cell products alone (approx. 1-2%) beyond 12 months [5,12,25,26]. As such, a variety of biomaterials have entered active development with the intent of providing a supportive scaffold that improves both acute cell retention and long-term cell viability [8,13,27].…”

Section: Discussionmentioning

confidence: 99%

The effect of encapsulation of cardiac stem cells within matrix-enriched hydrogel capsules on cell survival, post-ischemic cell retention and cardiac function

Mayfield¹,

Tilokee²,

Latham³

et al. 2014

Biomaterials

112

106

View full text Add to dashboard Cite

Transplantation of ex vivo proliferated cardiac stem cells (CSCs) is an emerging therapy for ischemic cardiomyopathy but outcomes are limited by modest engraftment and poor long-term survival. As such, we explored the effect of single cell microencapsulation to increase CSC engraftment and survival after myocardial injection. Transcript and protein profiling of human atrial appendage sourced CSCs revealed strong expression the pro-survival integrin dimers αVβ3 and α5β1-thus rationalizing the integration of fibronectin and fibrinogen into a supportive intracapsular matrix. Encapsulation maintained CSC viability under hypoxic stress conditions and, when compared to standard suspended CSC, media conditioned by encapsulated CSCs demonstrated superior production of pro-angiogenic/cardioprotective cytokines, angiogenesis and recruitment of circulating angiogenic cells. Intra-myocardial injection of encapsulated CSCs after experimental myocardial infarction favorably affected long-term retention of CSCs, cardiac structure and function. Single cell encapsulation prevents detachment induced cell death while boosting the mechanical retention of CSCs to enhance repair of damaged myocardium.

show abstract

Section: Discussionmentioning

confidence: 99%

The effect of encapsulation of cardiac stem cells within matrix-enriched hydrogel capsules on cell survival, post-ischemic cell retention and cardiac function

Mayfield¹,

Tilokee²,

Latham³

et al. 2014

Biomaterials

112

106

View full text Add to dashboard Cite

show abstract

“…[71] This finding is underlined by a recently published meta-analysis. [72] In this respect, large scaled phase 3 trials are on the way to identify the effects of BMMNCs on clinical outcome and mortality in patients with acute myocardial infarction or ischemic cardiomyopathy (BAMI, NCT01569178; REPEAT, NCT01693042). …”

Section: Bone-marrow-derived and Mobilized Cd34+ Cells For Cell-basedmentioning

confidence: 99%

Current Status of Cell-Based Therapy for Heart Failure

Jakob

Landmesser

2013

Curr Heart Fail Rep

View full text Add to dashboard Cite

In the last two decades, morbidity and mortality of patients with chronic heart failure could be further reduced by improved pharmacological and cardiac device therapies. However, despite these advances, there is a substantial unmet need for novel therapies, ideally specifically addressing repair and regeneration of the damaged or lost myocardium and its vasculature, given the limited endogenous potential for renewal of cardiomyocytes in adults. In this respect, cardiac cell-based therapies have gained substantial attention and have entered clinical feasibility and safety studies a decade ago. Different cell-types have been used, including bone marrow-derived mononuclear cells, bone marrow-derived mesenchymal stem cells, mobilized CD34+ cells, and more recently cardiac-derived c-kit+ stem cells and cardiosphere-derived cells. Some of these studies have suggested a potential of cell-based therapies to reduce cardiac scar size and to improve cardiac function in patients with ischemic cardiomyopathy. While first clinical trials examining the impact of cardiac cell-based therapy on clinical outcome have now been initiated, improved understanding of underlying mechanisms of action of cell-based therapies may lead to strategies for optimization of the cardiac repair potential of the applied cells. In experimental studies, direct in vivo reprogramming of cardiac fibroblasts towards cardiomyocytes, and microRNA-based promotion of cardiomyocyte proliferation and cardiac repair have recently been reported that may represent novel therapeutic approaches for cardiac regeneration that would not need cell-administration but rather directly stimulate endogenous cardiac regeneration. This review will focus mainly on recently completed clinical trials (within the last 2 years) investigating cardiac cell-based therapies and the current status of experimental studies for cardiac cell-based repair and regeneration with a potential for later translation into clinical studies in the future. AbstractIn the last two decades, morbidity and mortality of patients with chronic heart failure could be further reduced by improved pharmacological and cardiac device therapies.However, despite these advances, there is a substantial unmet need for novel therapies ideally specifically addressing repair and regeneration of the damaged or lost myocardium and its vasculature, given the limited endogenous potential for renewal of cardiomyocytes in adults.In this respect, cardiac cell-based therapies have gained substantial attention and

show abstract

“…[3][4][5][6] Only a small number of participants have been enrolled into most studies, but some meta-analyses have, nevertheless, been performed to evaluate the benefit of BMSC therapy for cardiac repair. [7][8][9] For example, in one meta-analysis the investigators included 50 studies (a total of 2,625 patients), and reported that BMSCs improved left ventricular ejection fraction (LVEF), reduced infarct size, and limited remodelling in patients with ischaemic heart disease (IHD), and that these benefits seemed to persist during long-term follow-up. 8 Similarly, the authors of a 2014 Cochrane Systematic Review, which included 23 randomized controlled trials involving 1,255 participants, reported that BMSC treatment can improve LVEF, mortality, and performance status in the long term (after at least 1 year) in individuals with IHD and heart failure.…”

mentioning

confidence: 99%

“…[7][8][9] For example, in one meta-analysis the investigators included 50 studies (a total of 2,625 patients), and reported that BMSCs improved left ventricular ejection fraction (LVEF), reduced infarct size, and limited remodelling in patients with ischaemic heart disease (IHD), and that these benefits seemed to persist during long-term follow-up. 8 Similarly, the authors of a 2014 Cochrane Systematic Review, which included 23 randomized controlled trials involving 1,255 participants, reported that BMSC treatment can improve LVEF, mortality, and performance status in the long term (after at least 1 year) in individuals with IHD and heart failure. 9 Meta-analyses are considered the highest level of evidence and might have a major effect on future health policy decisions; therefore, ensuring their accuracy is of paramount importance.…”

mentioning

confidence: 99%

“…However, many of studies of BMSC-based cardiac repair were statistically underpowered, preliminary, 4,6,8 Furthermore, substantial differences exist between these trials, in that the investigators used different cell types, delivery methods, cell injection numbers, study designs, baseline characteristics of patients, and cardiac imaging modalities. Results of meta-analyses can be misleading if these differences are not accounted for.…”

mentioning

confidence: 99%

See 1 more Smart Citation