Imaging Long-Term Fate of Intramyocardially Implanted Mesenchymal Stem Cells in a Porcine Myocardial Infarction Model

Perin, Emerson C.; Tian, Mei; Marini, Frank C.; Silva, Guilherme V.; Zheng, Yi; Baimbridge, Fred; Quan, Xin; Fernandes, Marlos R.; Gahremanpour, Amir; Young, Daniel; Paolillo, Vincenzo; Mukhopadhyay, Utpal; Borne, Agatha; Uthamanthil, Rajesh; Brammer, David W.; Jackson, J.; Decker, William K.; Najjar, Amer; Thomas, Michael W.; Volgin, Andrei; Rabinovich, Brian A.; Soghomonyan, Suren; Jeong, Hwan Jeong; Rios, Jesse; Steiner, David; Robinson, Simon N.; Mawlawi, Osama; Tinsu, Pan; Stafford, Jason; Kundra, Vikas; Li, Chun; Alauddin, Mian M.; Willerson, James T.; Shpall, Elizabeth J.; Gelovani, Juri G.

doi:10.1371/journal.pone.0022949

Cited by 59 publications

(35 citation statements)

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“…31 In a porcine model, enhanced survival of MSCs demonstrated by manganese-enhanced MRI and PET correlated with improved myocardial function. 14,28 Furthermore, this study by Templin et al 3 confirms survival of transplanted hiPSCs when optimized by the MSCs. Although there are conflicting data on in vivo stem cell survival, these studies offer promise to cell therapy in cardiovascular diseases.…”

Section: Article See P 430supporting

confidence: 58%

Is Reliable In Vivo Detection of Stem Cell Viability Possible in a Large Animal Model of Myocardial Injury?

Yang

2012

Circulation

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Section: Article See P 430supporting

confidence: 58%

Is Reliable In Vivo Detection of Stem Cell Viability Possible in a Large Animal Model of Myocardial Injury?

Yang

2012

Circulation

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“…Repetitive, long-term (up to 5 months) PET/CT studies of MSCs expressing HSV1-tk were conducted with a porcine model of myocardial infarction. Cell proliferation peaked at 33–35 days after injection in peri-infarct regions, but surprisingly, most of the transplanted cells were found in the major cardiac lymphatic vessels and lymph nodes 75 .…”

Section: Imaging Of Cell Fate and Host Environmentmentioning

confidence: 98%

Clinical imaging in regenerative medicine

et al. 2014

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In regenerative medicine, clinical imaging is indispensable for characterizing damaged tissue and for measuring the safety and efficacy of therapy. However, the ability to track the fate and function of transplanted cells with current technologies is limited. Exogenous contrast labels such as nanoparticles give a strong signal in the short term but are unreliable long term. Genetically encoded labels are good both short- and long-term in animals, but in the human setting they raise regulatory issues related to the safety of genomic integration and potential immunogenicity of reporter proteins. Imaging studies in brain, heart and islets share a common set of challenges, including developing novel labeling approaches to improve detection thresholds and early delineation of toxicity and function. Key areas for future research include addressing safety concerns associated with genetic labels and developing methods to follow cell survival, differentiation and integration with host tissue. Imaging may bridge the gap between cell therapies and health outcomes by elucidating mechanisms of action through longitudinal monitoring.

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“…pMSCs are multipotent and have the capacity for neural, adipose and osteogenic differentiation [8,9]. MSCs from large animals such as the pig offer great potential to investigate cell differentiation and cell fate.…”

Section: Introductionmentioning

confidence: 99%

Characteristics and neural-like differentiation of mesenchymal stem cells derived from foetal porcine bone marrow

Liu

et al. 2013

Bioscience Reports

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MSCs (mesenchymal stem cells) are a stem cell source that can be easily obtained from bone marrow. Despite the increasing importance of the pig as a large animal model, little is known about foetal pMSCs (porcine MSCs). In this study, we observed the gene expression of pluripotent markers in foetal pMSCs and the capacity of pMSCs to differentiate into adipocytes, osteocytes and neural-like cells using quantitative RT–PCR (reverse transcription–PCR), normal histological staining and immunohistochemistry. Foetal pMSCs have either a spindle or a flattened shape, and flow cytometry revealed the expression of the MSC-related proteins CD44 and CD105 (endoglin) but not CD34 and CD45. pMSCs express pluripotent markers such as Oct4 (octamer-binding transcription factor 4) and Nanog at the protein and mRNA levels. qRT-PCR (quantitative real-time PCR) analyses revealed that pMSCs expressed nestin [for NSCs (neural stem cells)]. Immunocytochemical and RT–PCR data showed that 29% and 23% of pMSCs expressed MAP2 (microtubule-associated protein 2) for neurons and β-tubulin III (Tuj1) for immature neurons, respectively, after induction of neural differentiation. These findings demonstrate the plasticity of pMSCs and their potential for use in cellular replacement therapy for neural diseases.

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Imaging Long-Term Fate of Intramyocardially Implanted Mesenchymal Stem Cells in a Porcine Myocardial Infarction Model

Cited by 59 publications

References 50 publications

Is Reliable In Vivo Detection of Stem Cell Viability Possible in a Large Animal Model of Myocardial Injury?

Is Reliable In Vivo Detection of Stem Cell Viability Possible in a Large Animal Model of Myocardial Injury?

Clinical imaging in regenerative medicine

Characteristics and neural-like differentiation of mesenchymal stem cells derived from foetal porcine bone marrow

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