Bone marrow–derived mononuclear cell transplantation improves myocardial recovery by enhancing cellular recruitment and differentiation at the infarction site

Mäkelä, Jussi; Ylitalo, Kari; Lehtonen, Siri; Dahlbacka, Sebastian; Niemelä, Eija; Kiviluoma, Kai; Rimpiläinen, Jussi; Alaoja, Hanna; Paavonen, Timo; Lehenkari, Petri; Juvonen, Tatu; Anttila, Vesa

doi:10.1016/j.jtcvs.2007.05.004

Cited by 30 publications

(11 citation statements)

References 20 publications

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“…Our fi ndings disagree with some reports that mononuclears containing fractions of hemopoietic stem cells and multipotent stromal cells can differentiate into practically all cardiac tissues [10,12]. However, impossibility of replacement of damaged CMC with transplanted mononuclears does not rule out their therapeutic effect consisting in stimulation of myocardial reparation due to production of paracrine factors by transplanted cells.…”

Section: A B C Dcontrasting

confidence: 99%

Directions of Migration of Bone Marrow Mononuclears after Intracoronary Transventricular Injection

et al. 2009

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Directions of migration of mononuclear bone marrow cells after intracoronary transventricular injection procedure developed by us were experimentally studied. After nonselective injection of cells into the right and left coronary arteries in rats, the labeled cells were detected only in the damaged zone of the myocardium. Localization of transplanted mononuclears in the scar attests to their homing into the damaged zone. Numerous cells were found in the red pulp of the spleen and solitary cells were detected in the liver and lungs. In the heart, the labeled transplanted cells were detected only in the scar zone at all terms of the study; they were not incorporated into the vascular walls, but were surrounded by thick bundles of collagen fibers and probably underwent differentiation into fibroblasts. No data on possible differentiation of the transplanted cells into vascular cells or cardiomyocytes were obtained.

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Section: A B C Dcontrasting

confidence: 99%

Directions of Migration of Bone Marrow Mononuclears after Intracoronary Transventricular Injection

et al. 2009

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“…Wang et al analyzed 39 21 preclinical studies, including 382 animals, concerning MSC therapy for renal impairment, but did not address differences in cell source and immunologic issues.…”

Section: Noncardiac Meta-analyses Of Stem Cell Therapymentioning

confidence: 99%

Similar Effect of Autologous and Allogeneic Cell Therapy for Ischemic Heart Disease

Eding

Vesterinen

Spoel

et al. 2015

Circulation Research

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Rationale:In regenerative therapy for ischemic heart disease, use of both autologous and allogeneic stem cells has been investigated. Autologous cell can be applied without immunosuppression, but availability is restricted, and cells have been exposed to risk factors and aging. Allogeneic cell therapy enables preoperative production of potent cell lines and immediate availability of cell products, allowing off-the-shelf therapy. It is unknown which cell source is preferred with regard to improving cardiac function.Objective: We performed a meta-analysis of preclinical data of cell therapy for ischemic heart disease. Methods and Results:We conducted a systematic literature search to identify publications describing controlled preclinical trials of unmodified stem cell therapy in large animal models of myocardial ischemia. Data from 82 studies involving 1415 animals showed a significant improvement in mean left ventricular ejection fraction in treated compared with control animals (8.3%, 95% confidence interval, 7.1-9.5; P<0.001). Meta-regression revealed a similar difference in left ventricular ejection fraction in autologous (8.8%, 95% confidence interval, 7.3-10.3; n=981) and allogeneic (7.3%, 95% confidence interval, 4.4-10.2, n=331; P=0.3) cell therapies. Conclusions: Autologous and allogeneic cell therapy for ischemic heart disease show a similar improvement in

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“…Although this scenario remains speculative, Figure 8 illustrates this postulate, whereby enhanced proteolytic pathways occur post-MI and an echo effect of the delivered stem cells occurs, attenuating this process. Recognition that stem cell therapy interacts with alternative biological pathways moves us beyond the canonical belief that the use of stem cells is effective on post-MI remodeling only when transformation to cardiac-type cells occurs or when long-term engraftment is achieved (22, 47, 64, 84). …”

Section: Resultsmentioning

confidence: 99%

Myocardial Remodeling: Cellular and Extracellular Events and Targets

Dixon

Spinale

2011

Annu. Rev. Physiol.

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The focus of this review is on translational studies utilizing large-animal models and clinical studies that provide fundamental insight into cellular and extracellular pathways contributing to post–myocardial infarction (MI) left ventricle (LV) remodeling. Specifically, both large-animal and clinical studies have examined the potential role of endogenous and exogenous stem cells to alter the course of LV remodeling. Interestingly, there have been alterations in LV remodeling with stem cell treatment despite a lack of long-term cell engraftment. The translation of the full potential of stem cell treatments to clinical studies has yet to be realized. The modulation of proteolytic pathways that contribute to the post-MI remodeling process has also been examined. On the basis of recent large-animal studies, there appears to be a relationship between stem cell treatment post-MI and the modification of proteolytic pathways, generating the hypothesis that stem cells leave an echo effect that moderates LV remodeling.

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Bone marrow–derived mononuclear cell transplantation improves myocardial recovery by enhancing cellular recruitment and differentiation at the infarction site

Abstract: Autologous bone marrow-derived mononuclear cells at the infarcted area localize in the myocardium. The exact mechanism of recovery remains to be determined, but our findings may give new information concerning the cellular events that occur during cell therapy-enhanced recovery.

Cited by 30 publications

References 20 publications

Directions of Migration of Bone Marrow Mononuclears after Intracoronary Transventricular Injection

Directions of Migration of Bone Marrow Mononuclears after Intracoronary Transventricular Injection

Similar Effect of Autologous and Allogeneic Cell Therapy for Ischemic Heart Disease

Myocardial Remodeling: Cellular and Extracellular Events and Targets

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