A Distinctive MRI-Based Absolute Bias Correction Protocol for the Potential Labelling and In Vivo Tracking of Stem Cells in a TBI Mice Model

2019 ◽  
pp. 93-111
Author(s):  
Sushanta Kumar Mishra ◽  
Subash Khushu ◽  
Gurudutta Gangenahalli
Keyword(s):  
Stem Cells ◽  
Bias Correction ◽  
Mice Model ◽  
Absolute Bias

The differentiation of hematopoietic stem cells was reprogrammed in advanced tumor-bearing mice

2020 ◽  
Author(s):  
Jicong Du ◽  
Penglin Xia ◽  
Yuan Gao ◽  
Ying Cheng ◽  
Ruling Liu ◽  
...  
Keyword(s):  
Stem Cells ◽  
Hematopoietic Stem Cells ◽  
Cancer Progression ◽  
Multilineage Differentiation ◽  
Mice Model ◽  
Hematopoietic Stem ◽  
Culture Techniques ◽  
Tumor Bearing ◽  
Advanced Tumor

Abstract Background: Hematopoiesis and the differentiation of HSC have been proved to not only play important roles in cancer progression but also be changed or reprogrammed by the tumor microenvironment itself. In this study, we investigated the changes of HSCs differentiation in advanced tumor-bearing mice. Methods: The tumor-bearing mice model was established by subcutaneously inoculating with xenografts of B16-F10 mouse melanoma cells into the right back of male wild-type C57BL/6 mice. Hematopoietic stem cells and multilineage differentiation were evaluated using blood routine, HE-staining, flow cytometry assay and HSCs culture techniques. Results: The multilineage differentiation of hematopoietic stem cells was reprogrammed in vivo . Especially, the differentiations of megakaryocyte and erythrocyte were blocked , while myeloid cell and lymphoid cell differentiation was encouraged in advanced tumor-bearing mice. Conclusion: In this study we showed the potential mechanism of hematopoietic disorder in tumor condition from a respective of hematopoietic stem cell and multilineage differentiation, which provided new knowledge regarding cachexia.

scholarly journals A Pig-a conditional knock-out mice model mediated by Vav-iCre: stable GPI-deficient and mild hemolysis

2022 ◽  
Vol 11 (1) ◽  
Author(s):  
Yingying Chen ◽  
Hui Liu ◽  
Lijie Zeng ◽  
Liyan Li ◽  
Dan Lu ◽  
...  
Keyword(s):  
Stem Cells ◽  
Animal Model ◽  
Mouse Model ◽  
Paroxysmal Nocturnal Hemoglobinuria ◽  
Basic Research ◽  
Mice Model ◽  
Hematopoietic Stem ◽  
Knock Out ◽  
Knock Out Mice

AbstractParoxysmal nocturnal hemoglobinuria is a clonal disease caused by PIG-A mutation of hematopoietic stem cells. At present, there is no suitable PNH animal model for basic research, therefore, it is urgent to establish a stable animal model. We constructed a Pig-a conditional knock-out mice model by ES targeting technique and Vav-iCre. The expressions of GPI and GPI-AP were almost completely absent in CKO homozygote mice, and the proportion of the deficiency remained stable from birth. In CKO heterozygote mice, the proportion of the deficiency of GPI and GPI-AP was partially absent and decreased gradually from birth until it reached a stable level at 3 months after birth and remained there for life. Compared with normal C57BL/6N mice and Flox mice, pancytopenia was found in CKO homozygous mice, and leukopenia and anemia were found in CKO heterozygotes mice. Meanwhile, in CKO mice, the serum LDH, TBIL, IBIL, complement C5b-9 levels were increased, and the concentration of plasma FHb was increased. Hemosiderin granulosa cells can be seen more easily in the spleens of CKO mice. What’s more, CKO mice had stable transcription characteristics. In conclusion, our mouse model has stable GPI-deficient and mild hemolysis, which may be an ideal in vivo experimental model for PNH.

Mesenchymal stem cells can be specifically transplanted into the femur: a Magic result by Magnetism-induced cell target transplantation (MagiC-TT) in dual transgenic mice model

Blood ◽  
2014 ◽  
Vol 124 (21) ◽  
pp. 2416-2416
Author(s):  
Qianli Jiang ◽  
Hao Huang ◽  
Qiusui Mai ◽  
Jia peng Wang ◽  
Yuncong Lu ◽  
...  
Keyword(s):  
Magnetic Field ◽  
Stem Cells ◽  
Bone Marrow ◽  
Transgenic Mice ◽  
Cell Group ◽  
Wild Type ◽  
Mice Model ◽  
Cell Target

Abstract BACKGROUND: Mesenchymal stem cells (MSCs), like non-hematopoietic multipotent stem cells, are considered as the most promising stem cells for clinical use, such as treatment of aplastic anemia, graft-versus-host-disease after allogeneic hematopoietic stem cell (HSC) transplantation, as well as tissue engineering, etc. But the fate of MSC in vivo remains almost unknown, including its homing, proliferation and the interaction between MSC and surrounding cells. Target transplantation has been a dream of researchers for many years, especially for such important cells as MSC or HSC, and now it can be made possible by our self-established novel Magnetism-induced cell target transplantation (MagiC-TT). OBJECTIVE: To explore the distribution and survival of donor MSCs transplanted by Magnetism-induced cell target transplantation (MagiC-TT) in vivo, with dual fluorescent protein transgenic mice model. Methods and results: 1) Magnetized cells: the C57BL/6 RFP-MSCs were bought from Cyagen Biosciences Inc. (China) and were magnetized by self-made Au@Fe nano-particle, positive cells were sorted by MACS column. 2) Cell biology: Both magnetized and wild type (wt) cells were stained by Wright Giemsa and HE staining, as well as Prussian blue, there were no differences in cell morphology, while the particles of Au@Fe exist within or on the surface of magnetized cells. CCK8 method did not find any statistical significances in cell proliferation (P=0.802), cell cycle and cell viability. 3) In vitro study: In order to study the influence of magnetism to magnetized cells, cells' migration to magnetism and proliferation curve, transwell migration and matrigel migration assays were carried out. Within the magnetic field, magnetized cells can migrate through matrigel and transwell membrane much more efficiently, 174±22 vs. 2±1 per 200X microscopic vision (P<0.0001); they also can migrate horizontally towards magnetism in matrigel (showed in Fig.1A); magnetized cells even grow well on the roof of 24-plate (grows against gravity) in the culture medium. 4) In Vivo study: Twenty C57BL/6 female GFP transgenic mice were divided into magnetized cell group and non-magnetized cell group (10 in each), magnetized and wt cells were injected into the femur cavity of the mice in both groups respectively. All the mice in both groups had magnetic field (which is of the same magnitude as the one used in vitro) on its femur for 24h. At different time points, 1h, 24h, 72h and 3m after RFP-MSCs injection, bioluminescence by Xenogen IVIS Imaging System (Lumina), FACS analysis of peripheral blood, bone marrow, liver, spleen and thymus; fluorescence and confocal microscopy, together with real-time PCR for GFP and RFP cells in different tissue after mice total body perfusion fixation were performed. Femurs and humeri of recipients were decalcified with self-made semi-solid decalcification (SSD, 2010 ASH poster, no.2625) to clarify the distribution of RFP-MSCs, traditional methods were used as control. At 1h, most MSCs stayed in lung in non-magnetized cell group while few in magnetized cell group. 24h later, confocal microscopy showed that lots of RFP-MSCs exit within femur and knee joint in magnetized cells group (Fig. 1B) while few in control group, thus, demonstrating the success of MSCs target transplantation. At 72h (2d post withdrawal of magnetic field), microscopy and bioluminescence showed the presence of few MSC in the lung of non-magnetized cell group, while many MSCs presented in lung and femur in magnetized cell group, MSCs also appeared in spleen, kidney, gut and other organs, showing the slow release of target transplanted MSCs from femur. By real-time PCR and frozen sections, MSCs were found to survive for 3m in the bone, lung, liver, spleen, etc. in both groups. Discussion: This study shows that magnetized MSCs have extra potential of moving under magnetism and comparable biology with wild-type cells. MagIC-TT can help MSCs' homing to bone marrow effectively, withdrawal of magnetic field permits MSCs to migrate into many tissues such as lungs, liver and spleen etc. Donor MSCs can survive for at least 3m in vivo. CONCLUSION: This dual transgenic mice model demonstrated that target cell transplantation can be achieved by MagIC-TT technology, and that it is useful in studying MSC and its mechanism in vivo. MagIC-TT also can be used in other cell therapy, by helping cells migrate to target tissues and organs in the future. Figure 1 Figure 1. Disclosures No relevant conflicts of interest to declare.

scholarly journals Gigantol Targets Cancer Stem Cells and Destabilizes Tumors via the Suppression of the PI3K/AKT and JAK/STAT Pathways in Ectopic Lung Cancer Xenografts

Cancers ◽  
2019 ◽  
Vol 11 (12) ◽  
pp. 2032 ◽  
Author(s):  
Nattanan Losuwannarak ◽  
Arnatchai Maiuthed ◽  
Nakarin Kitkumthorn ◽  
Asada Leelahavanichkul ◽  
Sittiruk Roytrakul ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Stem Cells ◽  
Cell Proliferation ◽  
Cancer Stem Cells ◽  
Treatment Strategies ◽  
Tumor Initiation ◽  
Mice Model ◽  
Ki 67 ◽  
Targeting Therapy

Lung cancer has long been recognized as an important world heath concern due to its high incidence and death rate. The failure of treatment strategies, as well as the regrowth of the disease driven by cancer stem cells (CSCs) residing in the tumor, lead to the urgent need for a novel CSC-targeting therapy. Here, we utilized proteome alteration analysis and ectopic tumor xenografts to gain insight on how gigantol, a bibenzyl compound from orchid species, could attenuate CSCs and reduce tumor integrity. The proteomics revealed that gigantol affected several functional proteins influencing the properties of CSCs, especially cell proliferation and survival. Importantly, the PI3K/AKT/mTOR and JAK/STAT related pathways were found to be suppressed by gigantol, while the JNK signal was enhanced. The in vivo nude mice model confirmed that pretreatment of the cells with gigantol prior to a tumor becoming established could decrease the cell division and tumor maintenance. The results indicated that gigantol decreased the relative tumor weight with dramatically reduced tumor cell proliferation, as indicated by Ki-67 labeling. Although gigantol only slightly altered the epithelial-to-mesenchymal and angiogenesis statuses, the gigantol-treated group showed a dramatic loss of tumor integrity as compared with the well-grown tumor mass of the untreated control. This study reveals the effects of gigantol on tumor initiation, growth, and maintain in the scope that the cells at the first step of tumor initiation have lesser CSC property than the control untreated cells. This study reveals novel insights into the anti-tumor mechanisms of gigantol focused on CSC targeting and destabilizing tumor integrity via suppression of the PI3K/AKT/mTOR and JAK/STAT pathways. This data supports the potential of gigantol to be further developed as a drug for lung cancer.

Autologous transplantation of mesenchymal stem cells into the portal vein of the miniature pig; a preliminary experiment for NOTES approach

2019 ◽  
Vol 98 (9) ◽  
pp. 350-355
Keyword(s):  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Cell Therapy ◽  
Portal Vein ◽  
Liver Parenchyma ◽  
Miniature Pig ◽  
Hepatic Diseases ◽  
Study Results

Introduction: There is evidence that mesenchymal stem cells (MSCs) could trans-differentiate into the liver cells in vitro and in vivo and thus may be used as an unfailing source for stem cell therapy of liver disease. Combination of MSCs (with or without their differentiation in vitro) and minimally invasive procedures as laparoscopy or Natural Orifice Transluminal Endoscopic Surgery (NOTES) represents a chance for many patients waiting for liver transplantation in vain. Methods: Over 30 millions of autologous MSCs at passage 3 were transplanted via the portal vein in an eight months old miniature pig. The deposition of transplanted cells in liver parenchyma was evaluated histologically and the trans-differential potential of CM-DiI labeled cells was assessed by expression of pig albumin using immunofluorescence. Results: Three weeks after transplantation we detected the labeled cells (solitary, small clusters) in all 10 samples (2 samples from each lobe) but no diffuse distribution in the samples. The localization of CM-DiI+ cells was predominantly observed around the portal triads. We also detected the localization of albumin signal in CM-DiI labeled cells. Conclusion: The study results showed that the autologous MSCs (without additional hepatic differentiation in vitro) transplantation through the portal vein led to successful infiltration of intact miniature pig liver parenchyma with detectable in vivo trans-differentiation. NOTES as well as other newly developed surgical approaches in combination with cell therapy seem to be very promising for the treatment of hepatic diseases in near future.

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