Enhanced therapeutic effects on acute myocardial infarction with multiple intravenous transplantation of human cord blood mononuclear cells

et al. 2015

PLoS ONE

BackgroundWe previously showed that injection of peptide nanofibers (NF) combined with autologous bone marrow mononuclear cells (MNC) immediately after coronary artery ligation improves cardiac performance in pigs. To evaluate the clinical feasibility, this study was performed to determine the therapeutic time window for NF/MNC therapy in acute myocardial infarction (MI).Methods and ResultsA total of 45 adult minipigs were randomly grouped into 7 groups: sham or MI plus treatment with NS (normal saline), or NF or MNC alone at 1 day (1D) post-MI, or NF/MNC at 1, 4, or 7 days post-MI (N≥6). Cardiac function was assessed by echocardiography and ventricular catheterization. Compared with the NS control, pigs treated with NF/MNC at 1 day post-MI (NF/MC-1D) had the greatest improvement in left ventricle ejection fraction (LVEF; 55.1±1.6%; P<0.01 vs. NS) 2 months after MI. In contrast, pigs treated with either NF/MNC-4D or NF/MNC-7D showed 48.9±0.8% (P<0.05 vs. NS) and 43.5±2.3% (n.s. vs. NS) improvements, respectively. The +dP/dt and -dP/dt, infarct size and interstitial collagen content were also improved in the NF/MNC-1D and -4D groups but not in the -7D group. Mechanistically, MNC quality and the states of systemic inflammation and damaged heart tissue influence the therapeutic efficiency of NF/MNC therapy, as revealed by another independent study using 16 pigs.ConclusionsInjection of NF/MNC at 1 or 4 days, but not at 7 days post-MI, improves cardiac performance and prevents ventricular remodeling, confirming the importance of early intervention when using this therapy for acute MI.

Section: Discussionsupporting

confidence: 92%

“…Previous studies have demonstrated that only 1.3~2.6% of the administered cells were detected 1.5 hours after the injection [5]. It is now widely accepted that the effectiveness of cell therapy in improving cardiac function heavily depends on the cell retention numbers [6]. …”

Section: Introductionmentioning

confidence: 99%

The Time Window for Therapy with Peptide Nanofibers Combined with Autologous Bone Marrow Cells in Pigs after Acute Myocardial Infarction

Chang

et al. 2015

PLoS ONE

“…The data demonstrated that CD341 cells and/or MSCs aid cardiac repair. The outcomes were consistent with those reported previously [5,6,8]. At 2 weeks after transplantation, no significant improvement was observed in ventricular performance in terms of FS and LVEF in cell-treated groups.…”

Section: Discussionsupporting

confidence: 92%

Mesenchymal Stem Cells and Mononuclear Cells From Cord Blood: Cotransplantation Provides a Better Effect in Treating Myocardial Infarction

Stem Cells Translational Medicine

Yue²,

et al. 2016

The aim of this study was to evaluate the effect of cotransplanting mononuclear cells from cord blood (CB-MNCs) and mesenchymal stem cells (MSCs) as treatment for myocardial infarction (MI). Transplanting CD341 cells or MSCs separately has been shown effective in treating MI, but the effect of cotransplanting CB-MNCs and MSCs is not clear. In this study, MSCs were separated by their adherence to the tissue culture. The morphology, immunophenotype, and multilineage potential of MSCs were analyzed. CB-MNCs were separated in lymphocyte separation medium 1.077. CD341 cell count and viability were analyzed by flow cytometry. Infarcted male Sprague-Dawley rats in a specificpathogen-free grade were divided into four treatment groups randomly: group I, saline; group II, CB-MNCs; group III, MSCs; and group IV, CB-MNCs plus MSCs. The saline, and CB-MNCs and/or MSCs were injected intramyocardially in infarcted rats. Their cardiac function was evaluated by echocardiography. The myocardial capillary density was analyzed by immunohistochemistry. Both cell types induced an improvement in the left ventricular cardiac function and increased tissue cell proliferation in myocardial tissue and neoangiogenesis. However, CB-MNCs plus MSCs were more effective in reducing the infarct size and preventing ventricular remodeling. Scar tissue was reduced significantly in the CB-MNCs plus MSCs group. MSCs facilitate engraftment of CD341 cells and immunomodulation after allogeneic CD341 cell transplantation. Cotransplanting MSCs and CB-MNCs might be more effective than transplanting MSCs or CB-MNCs separately for treating MI. This study contributes knowledge toward effective treatment strategies for MI. STEM CELLS TRANSLATIONAL MEDICINE 2016;5:350-357 SIGNIFICANCEThis study assessed cotransplantation of hematopoietic stem cells (CD341 cells) and mesenchymal stem cells (MSCs) for treatment of myocardial infarction (MI) in a rat model. The results demonstrate that MSCs and mononuclear cells from cord blood may have synergistic effects and cotransplantation might be more effective in the treatment of MI than transplanting MSCs and CD341 cells separately. This study contributes knowledge toward a more effective treatment protocol for MI.

“…Apart from the choice of cells to be transplanted, the number cells retained in the myocardium can also affect overall cardiac function after cell therapy [15, 16]. Studies have demonstrated that the majority of the transplanted cells after intravenous transplantation were retained in other organs rather than in the heart [17].…”

Section: Introductionmentioning

confidence: 99%

Injection of Human Cord Blood Cells With Hyaluronan Improves Postinfarction Cardiac Repair in Pigs

Chang

Huang

Stem Cells Translational Medicine

et al. 2015

This study using healthy human cord blood mononuclear cells (CB-MNCs) to treat myocardial infarction provides preclinical evidence that combined injection of hyaluronan and human CB-MNCs after myocardial infarction significantly increases cell retention in the peri-infarct area, improves cardiac performance, and prevents cardiac remodeling. Moreover, using healthy cells to replace dysfunctional autologous cells may constitute a better strategy to achieve heart repair and regeneration.