Immunological Barriers to Stem-Cell Based Cardiac Repair

Karabekian, Zaruhi; Posnack, Nikki Gillum; Sarvazyan, Narine

doi:10.1007/s12015-010-9202-x

Cited by 26 publications

(21 citation statements)

References 105 publications

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“…Furthermore, the fact that W8B2 1 CRSCs lack MHC class II proteins might allow them to escape recognition by effector CD4 1 T cells and thus evade immune recognition [31]. However, the lack of MHC class II molecule expression does not assure that W8B2 1 CRSCs are immune privilege as allogeneic transplantation of stem cells with similar MHC expression profile has been shown to cause immune rejection [32,33]. This is likely because host T lymphocytes can also be stimulated by MHC class I antigen of the donor cells.…”

Section: Discussionmentioning

confidence: 99%

Cardiac Repair With a Novel Population of Mesenchymal Stem Cells Resident in the Human Heart

et al. 2015

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Cardiac resident stem cells (CRSCs) hold much promise to treat heart disease but this remains a controversial field. Here, we describe a novel population of CRSCs, which are positive for W8B2 antigen and were obtained from adult human atrial appendages. W8B2 1 CRSCs exhibit a spindle-shaped morphology, are clonogenic and capable of self-renewal. W8B2 1 CRSCs show high expression of mesenchymal but not hematopoietic nor endothelial markers. W8B2 1 CRSCs expressed GATA4, HAND2, and TBX5, but not C-KIT, SCA-1, NKX2.5, PDGFRa, ISL1, or WT1. W8B2 1 CRSCs can differentiate into cardiovascular lineages and secrete a range of cytokines implicated in angiogenesis, chemotaxis, inflammation, extracellular matrix remodeling, cell growth, and survival. In vitro, conditioned medium collected from W8B2 1 CRSCs displayed prosurvival, proangiogenic, and promigratory effects on endothelial cells, superior to that of other adult stem cells tested, and additionally promoted survival and proliferation of neonatal rat cardiomyocytes. Intramyocardial transplantation of human W8B2 1 CRSCs into immunocompromised rats 1 week after myocardial infarction markedly improved cardiac function (~40% improvement in ejection fraction) and reduced fibrotic scar tissue 4 weeks after infarction. Hearts treated with W8B2 1 CRSCs showed less adverse remodeling of the left ventricle, a greater number of proliferating cardiomyocytes (Ki67 1 cTnT 1 cells) in the remote region, higher myocardial vascular density, and greater infiltration of CD163 1 cells (a marker for M2 macrophages) into the border zone and scar regions. In summary, W8B2 1 CRSCs are distinct from currently known CRSCs found in human hearts, and as such may be an ideal cell source to repair myocardial damage after infarction. STEM CELLS 2015;33:3100-3113 SIGNIFICANCE STATEMENTWe have isolated a new type of adult stem cell from human heart tissue, which carries markers different from known cardiac resident stem cells. These cells can be rapidly expanded and have powerful regenerative effects when injected into the hearts of rats after heart attack, such that they greatly improve cardiac performance compared with controls that have also suffered heart attack. We showed these cells protect other cells from dying and promote growth of blood vessels, actions which assist cardiac regeneration. Importantly, their protective actions in this regard are superior to those of other adult stem cells that have shown some benefit in clinical trials after heart attack. These new stem cells have great potential for repairing the heart, and could be derived from the individual patients in need, avoiding any problem of immunorejection.

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Section: Discussionmentioning

confidence: 99%

Cardiac Repair With a Novel Population of Mesenchymal Stem Cells Resident in the Human Heart

et al. 2015

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“…In case of graft failure, the transplanted cells die first (eg, because of hypoxia or mechanical factors), which leads to secondary macrophage influx and clearance of dead cells (7). In case of graft rejection, specific stem cell immunophenotypes attract monocytes, macrophages, lymphocytes, and dendritic cells, which recognize, kill, and eliminate the transplanted cells (8).…”

Section: Contrast Agentmentioning

confidence: 99%

Intravenous Ferumoxytol Allows Noninvasive MR Imaging Monitoring of Macrophage Migration into Stem Cell Transplants

Khurana¹,

Nejadnik²,

Gawande³

et al. 2012

Radiology

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Purpose:To develop a clinically applicable imaging technique for monitoring differential migration of macrophages into viable and apoptotic matrix-associated stem cell implants (MASIs) in arthritic knee joints. Materials andMethods:With institutional animal care and use committee approval, six athymic rats were injected with intravenous ferumoxytol (0.5 mmol iron per kilogram of body weight) to preload macrophages of the reticuloendothelial system with iron oxide nanoparticles. Forty-eight hours later, all animals received MASIs of viable adipose-derived stem cells (ADSCs) in an osteochondral defect of the right femur and mitomycin-pretreated apoptotic ADSCs in an osteochondral defect of the left femur. One additional control animal each received intravenous ferumoxytol and bilateral scaffold-only implants (without cells) or bilateral MASIs without prior ferumoxytol injection. All knees were imaged with a 7.0-T magnetic resonance (MR) imaging unit with T2-weighted fast spin-echo sequences immediately after, as well as 2 and 4 weeks after, matrix-associated stem cell implantation. Signal-to-noise ratios (SNRs) of viable and apoptotic MASIs were compared by using a linear mixedeffects model. MR imaging data were correlated with histopathologic findings. Results:All ADSC implants showed a slowly decreasing T2 signal over 4 weeks after matrix-associated stem cell implantation. SNRs decreased significantly over time for the apoptotic implants (SNRs on the day of matrix-associated stem cell implantation, 2 weeks after the procedure, and 4 weeks after the procedure were 16.9, 10.9, and 6.7, respectively; P = .0004) but not for the viable implants (SNRs on the day of matrix-associated stem cell implantation, 2 weeks after the procedure, and 4 weeks after the procedure were 17.7, 16.2, and 15.7, respectively; P = .2218). At 4 weeks after matrix-associated stem cell implantation, SNRs of apoptotic ADSCs were significantly lower than those of viable ADSCs (mean, 6.7 vs 15.7; P = .0013). This corresponded to differential migration of ironloaded macrophages into MASIs. Conclusion:Iron oxide loading of macrophages in the reticuloendothelial system by means of intravenous ferumoxytol injection can be utilized to monitor differential migration of bone marrow macrophages into viable and apoptotic MASIs in a rat model.

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“…Generation of a library of immune-compatible iPS or ES cells with defined epigenetic properties would circumvent such hassles but would still allow avoidance of posttransplant immunosuppression. [111][112][113] …”

Section: Epigenetic Regulation In Induced Pluripotent Stem Cellsmentioning

confidence: 99%

Epigenetic Modifications of Stem Cells

Zhou

Kim

Yuan

et al. 2011

Circulation Research

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Stem cells of all types are characterized by the ability to self-renew and to differentiate. Multiple lines of evidence suggest that both maintenance of stemness and lineage commitment, including determination of the cardiomyogenic lineage, are tightly controlled by epigenetic mechanisms such as DNA methylation, histone modifications, and ATP-dependent chromatin remodeling. Epigenetic mechanisms are intrinsically reversible, interdependent, and highly dynamic in regulation of chromatin structure and specific gene transcription programs, thereby contributing to stem cell homeostasis. Here, we review the current understanding of epigenetic mechanisms involved in regulation of stem cell self-renewal and differentiation and in the control of cardiac progenitor cell commitment during heart development. Further progress in this area will help to decipher the epigenetic landscape in stem and progenitor cells and facilitate manipulation of stem cells for regenerative applications.

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Immunological Barriers to Stem-Cell Based Cardiac Repair

Cited by 26 publications

References 105 publications

Cardiac Repair With a Novel Population of Mesenchymal Stem Cells Resident in the Human Heart

Cardiac Repair With a Novel Population of Mesenchymal Stem Cells Resident in the Human Heart

Intravenous Ferumoxytol Allows Noninvasive MR Imaging Monitoring of Macrophage Migration into Stem Cell Transplants

Epigenetic Modifications of Stem Cells

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