A randomized study of transendocardial injection of autologous bone marrow mononuclear cells and cell function analysis in ischemic heart failure (FOCUS-HF)

Perin, Emerson C.; Silva, Guilherme V.; Henry, Timothy D.; Cabreira-Hansen, Maria G.; Moore, Warren H.; Coulter, Stephanie; Herlihy, James; Fernandes, Marlos R.; Cheong, Benjamin; Flamm, Scott D.; Traverse, Jay H.; Zheng, Yi; Smith, Deirdre; Shaw, S.; Westbrook, Lynette; Olson, Rachel E.; Patel, Dipsu; Gahremanpour, Amir; Canales, John; Vaughn, William K.; Willerson, James T.

doi:10.1016/j.ahj.2011.01.028

Cited by 162 publications

(116 citation statements)

References 29 publications

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“…Regenerative medicine has been developed in recent years, such as mesenchymal stem cell (MSC) transplantation to repair myocardial infarction (MI) and restore heart function in both animal experiments1, 2, 3, 4 and patients 5, 6, 7, 8, 9, 10. There is mounting evidence that MSCs help repair or regenerate damaged tissues, primarily by means of secreting paracrine factors,11 including antiapoptotic factors,12 proangiogenic factors,13 and exosomes,14 rather than via the differentiation into cardiomyocytes 15, 16, 17…”

Section: Introductionmentioning

confidence: 99%

Engineered Exosomes With Ischemic Myocardium‐Targeting Peptide for Targeted Therapy in Myocardial Infarction

Wang

Chen

Zhao

et al. 2018

JAHA

252

206

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BackgroundExosomes are membranous vesicles generated by almost all cells. Recent studies demonstrated that mesenchymal stem cell–derived exosomes possessed many effects, including antiapoptosis, anti‐inflammatory effects, stimulation of angiogenesis, anticardiac remodeling, and recovery of cardiac function on cardiovascular diseases. However, targeting of exosomes to recipient cells precisely in vivo still remains a problem. Ligand fragments or homing peptides discovered by phage display and in vivo biopanning methods fused to the enriched molecules on the external part of exosomes have been exploited to improve the ability of exosomes to target specific tissues or organs carrying cognate receptors. Herein, we briefly elucidated how to improve targeting ability of exosomes to ischemic myocardium.Methods and ResultsWe used technology of molecular cloning and lentivirus packaging to engineer exosomal enriched membrane protein (Lamp2b) fused with ischemic myocardium‐targeting peptide CSTSMLKAC (IMTP). In vitro results showed that IMTP‐exosomes could be internalized by hypoxia‐injured H9C2 cells more efficiently than blank‐exosomes. Compared with blank‐exosomes, IMTP‐exosomes were observed to be increasingly accumulated in ischemic heart area (P<0.05). Meanwhile, attenuated inflammation and apoptosis, reduced fibrosis, enhanced vasculogenesis, and cardiac function were detected by mesenchymal stem cell–derived IMTP‐exosome treatment in ischemic heart area.ConclusionsOur research concludes that exosomes engineered by IMTP can specially target ischemic myocardium, and mesenchymal stem cell–derived IMTP‐exosomes exert enhanced therapeutic effects on acute myocardial infarction.

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Section: Introductionmentioning

confidence: 99%

Engineered Exosomes With Ischemic Myocardium‐Targeting Peptide for Targeted Therapy in Myocardial Infarction

Wang

Chen

Zhao

et al. 2018

JAHA

252

206

View full text Add to dashboard Cite

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“…subset must be functionally evaluated before clinical use; for instance, in the treatment of cardiac disease (18).…”

mentioning

confidence: 99%

Clonal precursor of bone, cartilage, and hematopoietic niche stromal cells

Chan

Lindau

Jiang

et al. 2013

Proc. Natl. Acad. Sci. U.S.A.

119

127

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Organs are composites of tissue types with diverse developmental origins, and they rely on distinct stem and progenitor cells to meet physiological demands for cellular production and homeostasis. How diverse stem cell activity is coordinated within organs is not well understood. Here we describe a lineage-restricted, self-renewing common skeletal progenitor (bone, cartilage, stromal progenitor; BCSP) isolated from limb bones and bone marrow tissue of fetal, neonatal, and adult mice. The BCSP clonally produces chondrocytes (cartilage-forming) and osteogenic (bone-forming) cells and at least three subsets of stromal cells that exhibit differential expression of cell surface markers, including CD105 (or endoglin), Thy1 [or CD90 (cluster of differentiation 90)], and 6C3 [ENPEP glutamyl aminopeptidase (aminopeptidase A)]. These three stromal subsets exhibit differential capacities to support hematopoietic (blood-forming) stem and progenitor cells. Although the 6C3-expressing subset demonstrates functional stem cell niche activity by maintaining primitive hematopoietic stem cell (HSC) renewal in vitro, the other stromal populations promote HSC differentiation to more committed lines of hematopoiesis, such as the B-cell lineage. Gene expression analysis and microscopic studies further reveal a microenvironment in which CD105-, Thy1-, and 6C3-expressing marrow stroma collaborate to provide cytokine signaling to HSCs and more committed hematopoietic progenitors. As a result, within the context of bone as a blood-forming organ, the BCSP plays a critical role in supporting hematopoiesis through its generation of diverse osteogenic and hematopoietic-promoting stroma, including HSC supportive 6C3(+) niche cells.endochondral ossification | lymphopoiesis

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“…[21][22][23][24][25] In the Focus-HF trial, Perin et al were able to demonstrate that intramyocardial transplantation of autologous bone marrow mononuclear cells in patients with ischemic heart failure improved quality of life and exercise capacity. 26 They attributed these beneficial effects of stem cells to improved perfusion of the ischemic myocardium. Similarly, Losordo et al showed that intramyocardial application of CD34+ stem cells in patients with refractory angina significantly reduced frequency and duration of anginal episodes.…”

Section: Clinical Effects Of Stem Cell Therapy In Ischemic Heart Failurementioning

confidence: 99%

Stem Cell Therapy in Patients with Heart Failure

Vrtovec¹,

Poglajen²,

Haddad³

2013

Methodist DeBakey Cardiovascular Journal

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A randomized study of transendocardial injection of autologous bone marrow mononuclear cells and cell function analysis in ischemic heart failure (FOCUS-HF)

Cited by 162 publications

References 29 publications

Engineered Exosomes With Ischemic Myocardium‐Targeting Peptide for Targeted Therapy in Myocardial Infarction

Engineered Exosomes With Ischemic Myocardium‐Targeting Peptide for Targeted Therapy in Myocardial Infarction

Clonal precursor of bone, cartilage, and hematopoietic niche stromal cells

Stem Cell Therapy in Patients with Heart Failure

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