Abstract 248: Comparison Of Transplantation Of Bone Marrow-derived Stem Cells, Adipose-derived Stem Cells And Endometrium- Derived Stem Cells In The Infarcted Heart

2014 ◽  
Vol 115 (suppl_1) ◽  
Author(s):  
Xin Yang Hu ◽  
Kan Wang ◽  
Jian-an Wang
Keyword(s):  
Myocardial Infarction ◽  
Stem Cells ◽  
Bone Marrow ◽  
Flow Cytometry ◽  
Adipose Tissue ◽  
Cardiac Function ◽  
Control Cell ◽  
Intramyocardial Injection ◽  
Infarcted Heart

Background: A variety of adult stem cells have been transplanted into the infarcted heart to cure myocardial infarction(MI), however, comparative studies are lacking to show more suitable source of cells for transplantation. Mesenchymal stem cells hold promise for myocardial regeneration therapy. Derivation of these cells from the endometrium tissue might be easier compared to bone marrow and adipose tissue. However,the in vivo fate of endometrium stem cells (EnSCs) in the infarcted heart has never been compared directly to mesenchymal cells derived from bone marrow(BMMSCs) and adipose tissue(AdMSCs). Methods: EnSCs, AdMSCs and BMMSCs were isolated from healthy donors were characterized using flow cytometry for surface markers identification and microscopy for cell morphology. They were characterized with β-actin promoter driving firefly luciferase and green fluorescent protein (Fluc-GFP) double fusion reporter gene, and were characterized using flow cytometry, bioluminescence imaging (BLI) and luminometry. Cell proliferation was tested by CCK-8 kit, colony forming unit(CFU) was stained by crystal violet staining and apoptosis ratio were detected by TUNEL assay. Rat (n=8/group) underwent myocardial infarction followed by intramyocardial injection of 5х105 EnSCs, AdMSCs and BMMSCs, or saline (negative control). Cell survival was measured using BLI for 6 weeks and cardiac function was monitored by echocardiography and hemodynamics analysis. Ventricular morphology was assessed using histology. Results: EnSCs, AdMSCs and BMMSCs were CD29+, CD90+, CD105+, shared similar morphology, but EnSCs had best proliferation, colony-forming and anti-apoptosis activity of 3 types of MSCs. Cells expressed Fluc reporter genes in a number-dependent fashion, as confirmed by luminometry. After cardiac transplantation, transplantation of EnSCs was better capable of preserving ventricular function and dimensions than others, as confirmed by echo test, PV-loops and histology. Conclusions: This is the first study comparing the in in vitro and in vivo behavior of 3 types of MSCs in the infarcted heart. AdMSCs and BMMSCs do not tolerate well in the cardiac environment, resulting in more cell death andworse cardiac function than EnSCs groups.

Effect of G-CSF and Intramyocardial Injection of Bone Marrow Cells on Cardiac Function in Mouse Model of Myocardial Infarction: A Word for Neo-Vasculogenesis.

Blood ◽  
2004 ◽  
Vol 104 (11) ◽  
pp. 2693-2693
Author(s):  
Larissa Verda ◽  
Kehuan Luo ◽  
Xiaoqiang Han ◽  
Andrew Wasserstrom ◽  
Jon Lomasney ◽  
...  
Keyword(s):  
Myocardial Infarction ◽  
Stem Cells ◽  
Bone Marrow ◽  
Cardiac Function ◽  
Bone Marrow Cells ◽  
Ischemia Reperfusion ◽  
Myocardial Repair ◽  
Intramyocardial Injection ◽  
Border Zones ◽  
Marrow Cells

Abstract Recent studies suggest that primitive stem cells derived from bone marrow (BM) possess greater functional plasticity that was expected previously. It has been shown that bone marrow stem cells (BMSC) promote repairing mechanisms within myocardium following ischemia/reperfusion models of myocardial infarction (MI). Although it remains unclear whether BMSC transdifferentiate into or just fuse with cardiomyocytes, hemodynamic improvement after intramyocardial BMSC injection as well as after G-CSF injection has been demonstrated. Here, we investigated the contribution of BMSC versus G-CSF administration in myocardial repair following MI. Ten weeks old C57BL/6J mice were irradiated and transplanted with green fluorescent protein (GFP) positive bone marrow cells. Three months later, these mice underwent ligation of left anterior descending branch (LAD) of coronary artery and subsequently divided into three groups. One group (n=7) received G-CSF administration at 200ug/kg for 10 consecutive days. Another group (n=9) was injected with GFP+ marrow cells directly into ischemic heart. The third group was held as control (n=7). One month after coronary ligation we found significant improvement in cardiac function determined as a cardiac output, maximum power and dP/dt, in the G-CSF group compared to control. We evaluated the phenotype of GFP+ cells within myocardium in each treatment group by 488 nm laser-scanning confocal miscroscopy (of whole heart and slides) 35 days after LAD ligation. We found no evidence of myocardial transdifferentiation or cardiomyocyte cell fusion. Instead GFP+ capillaries were present and exclusively located in infarct border zones in both the G-CSF and bone marrow implantation groups, confirmed by anti-factor VIII staining. G-CSF administration and to a lesser extent marrow injection resulted in improved post infarct cardiac function indices. This beneficial effect is not due to transdifferentiation but could be explained by marrow injected or G-CSF mobilized endothelial progenitor cells (EPC) and/or cytokine mediated neo-vasculogenesis.

scholarly journals Comparative analysis of mouse bone marrow and adipose tissue mesenchymal stem cells for critical limb ischemia cell therapy

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Pegah Nammian ◽  
Seyedeh-Leili Asadi-Yousefabad ◽  
Sajad Daneshi ◽  
Mohammad Hasan Sheikhha ◽  
Seyed Mohammad Bagher Tabei ◽  
...  
Keyword(s):  
Stem Cells ◽  
Bone Marrow ◽  
Mesenchymal Stem Cells ◽  
Adipose Tissue ◽  
Cell Therapy ◽  
Femoral Artery ◽  
Critical Limb Ischemia ◽  
Limb Ischemia

Abstract Introduction Critical limb ischemia (CLI) is the most advanced form of peripheral arterial disease (PAD) characterized by ischemic rest pain and non-healing ulcers. Currently, the standard therapy for CLI is the surgical reconstruction and endovascular therapy or limb amputation for patients with no treatment options. Neovasculogenesis induced by mesenchymal stem cells (MSCs) therapy is a promising approach to improve CLI. Owing to their angiogenic and immunomodulatory potential, MSCs are perfect candidates for the treatment of CLI. The purpose of this study was to determine and compare the in vitro and in vivo effects of allogeneic bone marrow mesenchymal stem cells (BM-MSCs) and adipose tissue mesenchymal stem cells (AT-MSCs) on CLI treatment. Methods For the first step, BM-MSCs and AT-MSCs were isolated and characterized for the characteristic MSC phenotypes. Then, femoral artery ligation and total excision of the femoral artery were performed on C57BL/6 mice to create a CLI model. The cells were evaluated for their in vitro and in vivo biological characteristics for CLI cell therapy. In order to determine these characteristics, the following tests were performed: morphology, flow cytometry, differentiation to osteocyte and adipocyte, wound healing assay, and behavioral tests including Tarlov, Ischemia, Modified ischemia, Function and the grade of limb necrosis scores, donor cell survival assay, and histological analysis. Results Our cellular and functional tests indicated that during 28 days after cell transplantation, BM-MSCs had a great effect on endothelial cell migration, muscle restructure, functional improvements, and neovascularization in ischemic tissues compared with AT-MSCs and control groups. Conclusions Allogeneic BM-MSC transplantation resulted in a more effective recovery from critical limb ischemia compared to AT-MSCs transplantation. In fact, BM-MSC transplantation could be considered as a promising therapy for diseases with insufficient angiogenesis including hindlimb ischemia.

scholarly journals Comparison of Transplantation of Adipose Tissue- and Bone Marrow-Derived Mesenchymal Stem Cells in the Infarcted Heart

2009 ◽  
Vol 87 (5) ◽  
pp. 642-652 ◽  
Author(s):  
Koen E. A. van der Bogt ◽  
Sonja Schrepfer ◽  
Jin Yu ◽  
Ahmad Y. Sheikh ◽  
Grant Hoyt ◽  
...  
Keyword(s):  
Stem Cells ◽  
Bone Marrow ◽  
Mesenchymal Stem Cells ◽  
Adipose Tissue ◽  
Infarcted Heart

Bone marrow-derived mesenchymal stem cells inhibit T follicular helper cell in lupus-prone mice

Lupus ◽  
2017 ◽  
Vol 27 (1) ◽  
pp. 49-59 ◽  
Author(s):  
X Yang ◽  
J Yang ◽  
X Li ◽  
W Ma ◽  
H Zou
Keyword(s):  
Stem Cells ◽  
Bone Marrow ◽  
Flow Cytometry ◽  
T Cells ◽  
Lupus Nephritis ◽  
Bone Marrow Cells ◽  
Tfh Cells ◽  
Follicular Helper

Background The objective of this paper is to analyze the role of bone marrow-derived mesenchymal stem cells (BM-MSCs) on the differentiation of T follicular helper (Tfh) cells in lupus-prone mice. Methods Bone marrow cells were isolated from C57BL/6 (B6) mice and cultured in vitro, and surface markers were identified by flow cytometry. Naïve CD4+ T cells, splenocytes and Tfh cells were isolated from B6 mice spleens and co-cultured with BM-MSCs. The proliferation and the differentiation of CD4+ T cells and Tfh cells were analyzed by flow cytometry. Lupus-prone MRL/Mp-lpr/lpr (MRL/lpr) mice were treated via intravenous injection with expanded BM-MSCs, the differentiation of Tfh cells was detected, and the relief of lupus nephritis was analyzed. Results MSCs could be successfully induced from bone marrow cells, and cultured BM-MSCs could inhibit T cell proliferation dose-dependently. BM-MSCs could prevent Tfh cell development from naïve CD4+ T cells and splenocytes. BM-MSCs could inhibit IL-21 gene expression and cytokine production and inhibit isolated Tfh cells and STAT3 phosphorylation. In vivo study proved that BM-MSCs intravenous injection could effectively inhibit Tfh cell expansion and IL-21 production, alleviate lupus nephritis, and prolong the survival rate of lupus-prone mice. Conclusions BM-MSCs could effectively inhibit the differentiation of Tfh cells both in vitro and in vivo. BM-MSC treatment could relieve lupus nephritis, which indicates that BM-MSCs might be a promising therapeutic method for the treatment of SLE.

Treatment with 8F4, An Anti-PR1/HLA-A2 T Cell Receptor-Like Antibody, Reduces Established Acute Myeloid Leukemia and Eliminates Leukemia Stem Cells in Mice

Blood ◽  
2011 ◽  
Vol 118 (21) ◽  
pp. 766-766
Author(s):  
Anna Sergeeva ◽  
Hong He ◽  
Kathryn Ruisaard ◽  
Karen Clise-Dwyer ◽  
Lisa S St. John ◽  
...  
Keyword(s):  
Stem Cells ◽  
Bone Marrow ◽  
Flow Cytometry ◽  
Myeloid Leukemia ◽  
Bone Marrow Cells ◽  
Cell Receptor ◽  
Leukemia Stem Cells ◽  
Nsg Mice ◽  
Secondary Transfer

Abstract Abstract 766 PR1 (VLQELNVTV) is an HLA-A2-restricted leukemia-associated peptide from proteinase 3 and neutrophil elastase that is recognized by PR1-specific cytotoxic T lymphocytes that contribute to cytogenetic remission of myeloid leukemia. We developed a high affinity T cell receptor (TCR)-like mouse monoclonal antibody (8F4) that binds to a conformational epitope of the PR1/HLA-A2 complex. Flow cytometry and confocal microscopy of 8F4-labeled cells showed significantly higher PR1/HLA-A2 expression on AML blasts compared with normal leukocytes. Moreover, 8F4 mediated complement dependent cytolysis of AML blasts and Lin−CD34+CD38− leukemia stem cells (LSC), but not normal leukocytes. To investigate in vivo biological effects 8F4 on established leukemia, we established xenografts of primary human HLA-A2-positive AML in sublethally irradiated NOD.Cg-PrkdcscidIl2rgtm1Wjl/SzJ (NSG) mice. Leukemia engraftment was monitored in peripheral blood by flow cytometry. Mice with established PR1/HLA-A2-expressing leukemia were treated with twice-weekly intravenous injections of 200 μg 8F4 or isotype control antibody. Flow cytometry and histology analysis of tissues was used to assess leukemia burden and level of engraftment. After 5 weeks of treatment AML was reduced 300-fold in bone marrow of 8F4-treated mice compared to isotype-treated control animals (0.07 ± 0.06% hCD45+cells versus 20.4 ± 4.1%, n=5 mice per group). Moreover, leukemia stem cells (LSC, CD34+CD38−Lin-) were no longer detected in bone marrow of 8F4-treated mice, compared to 0.88 ± 0.24% in isotype-treated mice. Equally, AML was evident in the liver and spleen of isotype-treated mice (1.1 ± 0.16% and 0.32 ± 0.17%, respectively), but was undetectable in 8F4-treated mice (p<0.001). Similar results were obtained with AML from two additional patients, one with secondary AML (CMML) and one with AML-M7. Bone marrow contained 6.2 ± 3.0% (n=3) AML versus 41 ± 15% (n=2 mice; p=0.06) in the first case and 0.16 (n=1) versus 7.0 ± 4.1 (n=2) in the second case after 2–3 weeks of twice-weekly injection. To confirm 8F4-mediated elimination of LSC, we performed secondary transfer experiment with 1×106 bone marrow cells from 8F4- and isotype-treated mice, transplanted into recipient NSG mice, irradiated with 250 cGy. AML was undetectable in mice that received bone marrow from 8F4-treated animals versus 4.1 ± 2.4% (n=4) in bone marrow of mice that received cells from isotype- treated mice, determined at 16 weeks after secondary transfer. Because PR1/HLA-A2 expression on normal hematopoietic cells (HSC) is similar to LSC in AML patients, we sought to determine whether 8F4 treatment of NSG mice xenografted with CD34-selected umbilical cord blood resulted in elimination of xenograft. Fourteen weeks after transplant stable chimerism (4.1 - 7.7% hCD45+ cells) was established, mice were treated with 50 μg 8F4 intravenously and peripheral blood was monitored weekly for chimerism. Human CD45+ cells decreased to 0.35 – 0.95% by week 1, but increased to 1.9 – 2.1 % hCD45+ cells at week 3. Bone marrow at week three contained myeloid (CD13+CD33+) and lymphoid (CD19+) cells showing that while 8F4 has off- target effects against normal hematopoietic cells, HSC are preserved. This is consistent with our previous studies that showed no 8F4-mediated effect on colony formation of normal bone marrow cells. In conclusion, these results show that anti-PR1/HLA-A2 monoclonal antibody 8F4 is biologically active in vivo and selectively eliminates LSC, but not normal HSC. This justifies continued study of 8F4 as a novel therapy for AML. Disclosures: No relevant conflicts of interest to declare.

Adipose tissue-derived stem cells embedded with eNOS restore cardiac function in acute myocardial infarction model

2012 ◽  
Vol 154 (1) ◽  
pp. 2-8 ◽  
Author(s):  
Chun-zhi Shi ◽  
Xiao-ping Zhang ◽  
Zhong-wei Lv ◽  
Hui-li Zhang ◽  
Jian-zhong Xu ◽  
...  
Keyword(s):  
Myocardial Infarction ◽  
Acute Myocardial Infarction ◽  
Stem Cells ◽  
Adipose Tissue ◽  
Cardiac Function

scholarly journals Adipose tissue-derived mesenchymal stem cells have better restorative capacity than bone marrow-derived cells in a cerebellar ataxic rat model

2020 ◽  
Author(s):  
Rasha Att ◽  
Angie Ameen ◽  
Horeya Korayem ◽  
Noha Abogresha ◽  
Yasser El-Wazir
Keyword(s):  
Stem Cells ◽  
Bone Marrow ◽  
Mesenchymal Stem Cells ◽  
Adipose Tissue ◽  
Growth Factor ◽  
Motor Performance ◽  
Therapeutic Potential ◽  
Monosodium Glutamate ◽  
Control Group

IntroductionRegenerative treatment using stem cells represents a potentially effective therapy for cerebellar ataxia (CA). We compared the therapeutic potential of adipose tissue stem cells (ASCs) and bone marrow mesenchymal stem cells (BM-MSCs) in a rodent monosodium glutamate (MSG)-induced CA cell (BM-MSC) model.Material and methodsFemale Wistar rats (n = 40) were equally divided into a saline-treated control group and 3 MSG-induced CA groups randomly treated with either saline, or 1 × 106 ASCs or BM-MSCs. We assessed the following: 1) cerebellar motor functions in vivo (by Rotarod test, open-field test, and Quantitative gait analysis); 2) cerebellar histological architecture; and 3) cerebellar immunohistochemical examination of the Bax/Bcl-2 ratio as in indicator of apoptosis, and the levels of vascular endothelial growth factor (VEGF) and insulin-like growth factor-1 (IGF-1) as neuroprotective factors.ResultsTreatment with either of the MSCs improved MSG-induced poor motor performance, restored the disrupted Purkinje cell layer, decreased neuronal apoptosis and enhanced cerebellar VEGF and IGF-1 levels observed in CA rats. Adipose tissue stem cells showed superiority over BM-MSCs in the improvement of some motor performance parameters and cerebellar VEGF and IGF-1 levels.ConclusionsIn conclusion, both stem cell types induced structural, physiological, and biochemical improvement, with ASCs being best for treatment of CA.

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