Dynamic Imaging of Allogeneic Mesenchymal Stem Cells Trafficking to Myocardial Infarction

Kraitchman, Dara L.; Tatsumi, Mitsuaki; Gilson, Wesley D.; Ishimori, Takayoshi; Kedziorek, Dorota; Walczak, Piotr; Segars, W. Paul; Chen, Hunter H.; Fritzges, Danielle; Izbudak, Izlem; Young, Randell G.; Marcelino, Michelle; Pittenger, Mark F.; Solaiyappan, Meiyappan; Boston, Raymond C.; Tsui, B.M.W.; Wahl, Richard L.; Bulte, Jeff W.M.

doi:10.1161/circulationaha.105.537480

Cited by 547 publications

(480 citation statements)

References 47 publications

(66 reference statements)

Supporting

Mentioning

455

Contrasting

Unclassified

Order By: Relevance

“…When injected into fetal sheep, individual MSCs show site-specific differentiation [5]. In non-human adult primates, engraftment is lower, but both autologous and allogeneic MSCs can be detected in a wide range of organs [5][6][7]. However, a large proportion of MSCs are trapped either in the lung during first passage after intravenous infusion or in the microvasculature when infused on the arterial side [8,9].…”

Section: Introductionmentioning

confidence: 99%

Analysis of Tissues Following Mesenchymal Stromal Cell Therapy in Humans Indicates Limited Long-Term Engraftment and No Ectopic Tissue Formation

et al. 2012

View full text Add to dashboard Cite

Mesenchymal stromal cells (MSCs) are explored as a novel treatment for a variety of medical conditions. Their fate after infusion is unclear, and long-term safety regarding malignant transformation and ectopic tissue formation has not been addressed in patients. We examined autopsy material from 18 patients who had received human leukocyte antigen (HLA)-mismatched MSCs, and 108 tissue samples from 15 patients were examined by PCR. No signs of ectopic tissue formation or malignant tumors of MSC-donor origin were found on macroscopic or histological examination. MSC donor DNA was detected in one or several tissues including lungs, lymph nodes, and intestine in eight patients at levels from 1/100 to <1/1,000. Detection of MSC donor DNA was negatively correlated with time from infusion to sample collection, as DNA was detected from nine of 13 MSC infusions given within 50 days before sampling but from only two of eight infusions given earlier. There was no correlation between MSC engraftment and treatment response. We conclude that MSCs appear to mediate their function through a “hit and run” mechanism. The lack of sustained engraftment limits the long-term risks of MSC therapy.

show abstract

Section: Introductionmentioning

confidence: 99%

Analysis of Tissues Following Mesenchymal Stromal Cell Therapy in Humans Indicates Limited Long-Term Engraftment and No Ectopic Tissue Formation

et al. 2012

View full text Add to dashboard Cite

show abstract

“…Mesenchymal stem cells (MSCs) have a potential to regenerate cardiac myocytes following acute myocardial infarction (MI) [1]. However, mobilized cells into infarcted tissue are subject to cell death due to insufficient oxygen [2].…”

Section: Introductionmentioning

confidence: 99%

Over-expression of CXCR4 on mesenchymal stem cells augments myoangiogenesis in the infarcted myocardium

Zhang

Fan

Zhou

et al. 2008

Journal of Molecular and Cellular Cardiology

254

218

View full text Add to dashboard Cite

Bone marrow mesenchymal stem cells (MSCs) participate in myocardial repair following myocardial infarction. However, their in vivo reparative capability is limited due to lack of their survival in the infarcted myocardium. To overcome this limitation, we genetically engineered male rat MSCs overexpressing CXCR4 in order to maximize the effect of stromal cell-derived factor-1α (SDF-1α) for cell migration and regeneration. MSCs were isolated from adult male rats and cultured. Adenoviral transduction was carried out to over-express either CXCR4/green fluorescent protein (Ad-CXCR4/GFP) or Ad-null/GFP alone (control). Flow cytometry was used to identify and isolate GFP/CXCR4 over-expressing MSCs for transplantation. Female rats were assigned to one of four groups (n = 8 each) to receive GFP-transduced male MSCs (2 × 10 6 ) via tail vein injection 3 days after ligation of the left anterior descending (LAD) coronary artery: GFP-transduced MSCs (Ad-null/ GFP-MSCs, group 1) or MSCs over-expressing CXCR4/GFP (Ad-CXCR4/GFP-MSCs, group 2), or Ad-CXCR4/GFP-MSCs plus SDF-1α (50 ng/μl) (Ad-CXCR4/GFP-MSCs/SDF-1α, group 3), or Ad-miRNA targeting CXCR4 plus SDF-1α (Ad-miRNA/GFP-MSCs + SDF-1α treatment, group 4). Cardiodynamic data were obtained 4 weeks after induction of regional myocardial infarction (MI) using echocardiography after which hearts were harvested for immunohistochemical studies. The migration of GFP and Y-chromosome positive cells increased significantly in the peri-and infarct areas of groups 2 and 3 compared to control group (p<0.05), or miRNA-CXCR4 group (p<0.01). The number of CXCR4 positive cells in groups 2, 3 was intimately associated with angiogenesis and myogenesis. MSCs engraftment was blocked by pretreatment with miRNA (group 4). Cardiac function was significantly improved in rats receiving MSCs over-expressing CXCR4 alone or with SDF-1α. The up-regulation of matrix metalloproteinases (MMPs) by CXCR4 overexpressing MSCs perhaps facilitated their engraftment in the collagenous tissue of the infarcted area. CXCR4 overexpression led to enhance in vivo mobilization and engraftment of MSCs into ischemic area where these cells promoted neomyoangiogenesis and alleviated early signs of left ventricular remodeling.

show abstract

“…MI is, by nature, an irreversible injury. 6,7 After an MI, some heart cells are lost and others hibernate because they are underperfused. Cell transplantation and gene therapy offer the promise to replace the lost cells (myogenesis) and to perfuse the hibernating cells (angiogenesis).…”

Section: Discussionmentioning

confidence: 99%

Experimental study of bone marrow-derived mesenchymal stem cells combined with hepatocyte growth factor transplantation via noninfarct-relative artery in acute myocardial infarction

Yang

Wang

et al. 2006

Gene Ther

View full text Add to dashboard Cite

We investigated the impact of bone marrow-derived mesenchymal stem cells (BM-MSCs) alone or in combination with hepatocyte growth factor (HGF) transplantation via noninfarct-relative artery in a swine myocardial infarction (MI) model. Donor BM-MSCs were derived in vitro from swine auto-bone marrow cultures labeled by bromodeoxyuridine (BrdU) incorporation. Host MI swine model was created by ligating the distal left anterior descending artery. After 4 weeks, age-matched male MI swines were used for the transplantation. Male MI swines were transfused via noninfarctrelative artery with vehicle (control, n ¼ 6) or BrdU-labeled BM-MSCs (5 Â 10 6 ) alone (MSCs, n ¼ 6) or BrdU-labeled BM-MSCs (5 Â 10 6 ) combined with HGF (4 Â 10 9 PFU) (MSCs+HGF, n ¼ 6). To evaluate the collateral artery growth (Rentrop) and cardiac perfusion in these animals, gate cardiac perfusion imaging and coronary angiography were performed before and 4 weeks after transplantation, respectively. To assess the contribution of donor-originated cells in stimulation of cardiomyocyte regeneration and angiogenesis, immunohistochemistry for BrdU and a-smooth muscle actin (a-SMA) and quantitative image analysis were performed at 4 weeks after transplantation. The results are as follows: (1) BrdU-positive cells were detected in host myocardium in both MSCs and MSCs+HGF groups, but not in the vehicle group.Most BrdU-positive cells expressed myosin heavy chain b.(2) a-SMA -positive arteriole densities in the infarcted border area and infarcted area were increased significantly in both transplantation groups compared with the vehicle group. (3) Gate cardiac perfusion imaging demonstrated that the cardiac perfusion was significantly improved in transplantation groups compared with the vehicle group. (4) Ejection fraction and a-SMA-positive arteriole densities were increased significantly in both transplantation groups compared with the vehicle group. However, there was no difference in ejection fraction and a-SMA-positive arteriole densities between the MSCs group and the MSCs+HGF group. Growth of collateral arteries was not detected by coronary angiography in all three groups. In conclusion, the current study indicates that BMMSCs transplantation via noninfarct-relative artery stimulates cardiomyocyte regeneration and angiogenesis and improves cardiac function, but does not stimulate collateral artery growth. BM-MSCs transplantation combined with HGF therapy is not superior to BM-MSCs alone transplantation. BM-MSCs transplantation via noninfarct-relative artery may be an alternative for those patients who cannot be transplanted via infarct-relative artery in clinical practice. Gene Therapy (2006) 13, 1564-1568.

show abstract

Dynamic Imaging of Allogeneic Mesenchymal Stem Cells Trafficking to Myocardial Infarction

Cited by 547 publications

References 47 publications

Analysis of Tissues Following Mesenchymal Stromal Cell Therapy in Humans Indicates Limited Long-Term Engraftment and No Ectopic Tissue Formation

Analysis of Tissues Following Mesenchymal Stromal Cell Therapy in Humans Indicates Limited Long-Term Engraftment and No Ectopic Tissue Formation

Over-expression of CXCR4 on mesenchymal stem cells augments myoangiogenesis in the infarcted myocardium

Experimental study of bone marrow-derived mesenchymal stem cells combined with hepatocyte growth factor transplantation via noninfarct-relative artery in acute myocardial infarction

Contact Info

Product

Resources

About