Impact of Timing and Dose of Mesenchymal Stromal Cell Therapy in a Preclinical Model of Acute Myocardial Infarction

Richardson, J. David; Bertaso, A.; Psaltis, Peter J.; Frost, L.; Carbone, A.; Paton, Sharon; Nelson, Adam; Wong, D.; Worthley, M.; Gronthos, Stan; Zannettino, Andrew C.W.; Worthley, Stephen G.

doi:10.1016/j.cardfail.2013.03.011

Cited by 43 publications

(42 citation statements)

References 38 publications

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“…In rats with myocardial infarctions, it has been shown that the earlier the MSC transplantation was performed, the better the recovery of heart function was. Analysis of reduction in ventricular remodeling demonstrated that the effect of MSC on heart transplantation was dose dependent (Richardson et al, 2013). Due to their therapeutic potentials, MSCs are one of the most widely studied types of adult stem cells at present.…”

Section: Discussionmentioning

confidence: 99%

Rehmannia glutinosa oligosaccharide induces differentiation of bone marrow mesenchymal stem cells into cardiomyocyte-like cells

Wang

Xiaojuan

et al. 2016

Genet. Mol. Res.

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ABSTRACT. The aim of this study was to observe the effect of Rehmannia glutinosa oligosaccharide (RGO) on differentiation of bone marrow mesenchymal stem cells (MSCs) into cardiomyocytelike cells . Rat MSCs were isolated, treated, and grouped as follows: RGO treatment group, 5-azacytidine (5-aza) treatment group, RGO + 5-aza treatment group, and control group. Following a four-week induction period, cardiac troponin I (cTnI) levels in MSCs were quantified by chemiluminescence, and the levels of myocardial enzymes creatine kinase (CK) and creatine kinase isoenzyme-MB (CK-MB) were measured using a dry chemistry analyzer. The cTnIand connexin 43 (Cx43)-positive MSC population was identified by immunofluorescence, and expression levels of cTnI and Cx43 were analyzed by western blots. Following induction, cTnI, CK, and CK-MB levels were significantly higher in the RGO + 5-aza group as compared with the RGO and 5-aza groups (P < 0.05). In addition, fluorescence intensity of cTnI and Cx43 was higher in the RGO + 5-aza group as compared with the RGO and 5-aza groups. No cTnI-or Cx43-positive cells were detected in the control group. Western blot analysis further confirmed that cTnI and Cx43 were not expressed in the control group, while cTnI and Cx43 was higher in the RGO + 5-aza group than in the RGO and 5-aza groups. These results suggest that MSCs can be induced by RGO to differentiate into cardiomyocyte-like cells in vitro, and that RGO in combination with 5-aza enhance differentiation of MSCs.

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Section: Discussionmentioning

confidence: 99%

Rehmannia glutinosa oligosaccharide induces differentiation of bone marrow mesenchymal stem cells into cardiomyocyte-like cells

Wang

Xiaojuan

et al. 2016

Genet. Mol. Res.

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“…Although sharing the same mechanisms of action of BM-derived stem cells, CBMSC bring additional advantages ( Fig. 1), such as their larger availability and easier isolation, excluding any laborious sorting procedure [32,33]. The promise of CBMSC potential in regenerative medicine was already observed in a mouse model of AMI.…”

Section: Cortical Bone-derived Stem Cellsmentioning

confidence: 95%

“…Cell refinement can be achieved, for instance, by density centrifugation [13], magnetic-(MACS) [26,33] or fluorescence-activated cell sorting (FACS) [99] or by pre-in vitro priming [8,13,27,33,58,99,100]. Density centrifugation is often used to isolate mononuclear cells (BMMNC) from BM cell suspension [13,75], while MACS and FACS achieve a higher degree of selectivity by picking up cells according to their surface markers (cluster of differentiation, CD).…”

Section: Cell Choice Refinement Dosage and Timing Of Administrationmentioning

confidence: 99%

“…The advantages and limitations of each stem cell with regard to the possible emergence of ethical concerns (symbolized by ¥), the invasiveness and collection (from + to ++++), the isolation procedure, the abundance (from + to ++++), expansion and proliferation rate, the transdifferentiation capacity, the paracrine effects or/and cardiomyogenic potential, the survival and engraftment capacity as well as the immunogenic, oncogenic or teratogenic risks is given in the accessory side tables. The left table abridges bone marrow-derived stem cells [3,[19][20][21]27,28], cortical bone-derived stem cells [32,33], adipose tissue-derived stem cells [34,37,39,41] and gestation-related stem cells [42][43][44][45][46][47][48][49]51,54] and the right table abridges cardiac stem cells [57,59,60], skeletal muscle stem cells [62,63,66] and induced pluripotent stem cells [67,[69][70][71]. The human body scheme was constructed with images sourced from Servier Medical Art (http://www.servier.com/ Powerpoint-image-bank) and Cientic website (http://www.cientic.com/).…”

Section: Adipose Tissue-derived Stem Cellsmentioning

confidence: 99%

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Towards the standardization of stem cell therapy studies for ischemic heart diseases: Bridging the gap between animal models and the clinical setting

Trindade

Leite‐Moreira

Ferreira-Martins

et al. 2017

International Journal of Cardiology

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Today there is an increasing demand for heart transplantations for patients diagnosed with heart failure. Though, shortage of donors as well as the large number of ineligible patients hurdle such treatment option. This, in addition to the considerable number of transplant rejections, has driven the clinical research towards the field of regenerative medicine. Nonetheless, to date, several stem cell therapies tested in animal models fall by the wayside and when they meet the criteria to clinical trials, subjects often exhibit modest improvements. A main issue slowing down the admission of such therapies in the domain of human trials is the lack of protocol standardization between research groups, which hampers comparison between different approaches as well as the lack of thought regarding the clinical translation. In this sense, given the large amount of reports on stem cell therapy studies in animal models reported in the last 3 years, we sought to evaluate their advantages and limitations towards the clinical setting and provide some suggestions for the forthcoming investigations. We expect, with this review, to start a new paradigm on regenerative medicine, by evoking the debate on how to plan novel stem cell therapy studies with animal models in order to achieve more consistent scientific production and accelerate the admission of stem cell therapies in the clinical setting.

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“…MSC are a nontumorigenic, adherent fraction of heterogeneous cells that exhibit spindlelike morphology and clonogenic growth and express CD90, CD105, and CD73 but not CD34 or CD45 (5). After acute MI, MSC reverse both pathologic remodeling and scar size and enhance both ventricular mass and ejection fraction (6,7). Overall, MSC have proven to be a safe, attractive, and potent candidate for CCT.…”

Section: Advances In Knowledgementioning

confidence: 99%

Multimodality Molecular Imaging of Cardiac Cell Transplantation: Part I. Reporter Gene Design, Characterization, and Optical in Vivo Imaging of Bone Marrow Stromal Cells after Myocardial Infarction

Parashurama

Ahn²,

Ziv

et al. 2016

Radiology

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4 The complete list of authors is at the end of this article.q RSNA, 2016 Purpose:To use multimodality reporter-gene imaging to assess the serial survival of marrow stromal cells (MSC) after therapy for myocardial infarction (MI) and to determine if the requisite preclinical imaging end point was met prior to a follow-up large-animal MSC imaging study. Materials and Methods:Animal studies were approved by the Institutional Administrative Panel on Laboratory Animal Care. Mice (n = 19) that had experienced MI were injected with bone marrow-derived MSC that expressed a multimodality triple fusion (TF) reporter gene. The TF reporter gene (fluc2-egfp-sr39ttk) consisted of a human promoter, ubiquitin, driving firefly luciferase 2 (fluc2), enhanced green fluorescent protein (egfp), and the sr39tk positron emission tomography reporter gene. Serial bioluminescence imaging of MSC-TF and ex vivo luciferase assays were performed. Correlations were analyzed with the Pearson product-moment correlation, and serial imaging results were analyzed with a mixed-effects regression model.

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Impact of Timing and Dose of Mesenchymal Stromal Cell Therapy in a Preclinical Model of Acute Myocardial Infarction

Cited by 43 publications

References 38 publications

Rehmannia glutinosa oligosaccharide induces differentiation of bone marrow mesenchymal stem cells into cardiomyocyte-like cells

Rehmannia glutinosa oligosaccharide induces differentiation of bone marrow mesenchymal stem cells into cardiomyocyte-like cells

Towards the standardization of stem cell therapy studies for ischemic heart diseases: Bridging the gap between animal models and the clinical setting

Multimodality Molecular Imaging of Cardiac Cell Transplantation: Part I. Reporter Gene Design, Characterization, and Optical in Vivo Imaging of Bone Marrow Stromal Cells after Myocardial Infarction

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