Fetal liver stem cell transplantation for liver diseases

2019 ◽  
Vol 14 (7) ◽  
pp. 703-714 ◽  
Author(s):  
Aimaiti Yasen ◽  
Tuerhongjiang Tuxun ◽  
Shadike Apaer ◽  
Wending Li ◽  
Yusufukadier Maimaitinijiati ◽  
...  
Keyword(s):  
Stem Cells ◽  
Stem Cell ◽  
Stem Cell Transplantation ◽  
Cell Transplantation ◽  
Liver Diseases ◽  
Fetal Liver ◽  
Survival Rates ◽  
Current Status ◽  
Term Survival

Stem cell transplantation exhibited a promising lifesaving therapy for various end-stage liver diseases and could serve as a salvaging bridge until curative methods can be performed. In past decades, mature hepatocytes, liver progenitor cells, mesenchymal stem cells and induced pluripotent stem cells have been practiced in above settings. However, long-term survival rates and continuous proliferation ability of these cells in vivo are unsatisfactory, whereas, fetal liver stem cells (FLSCs), given their unique superiority, may be the best candidate for stem cell transplantation technique. Recent studies have revealed that FLSCs could be used as an attractive genetic therapy or regenerative treatments for inherited metabolic or other hepatic disorders. In this study, we reviewed current status and advancements of FLSCs-based treatment.

scholarly journals Molecular Imaging of Stem Cell Transplantation for Liver Diseases: Monitoring, Clinical Translation, and Theranostics

2016 ◽  
Vol 2016 ◽  
pp. 1-8 ◽  
Author(s):  
Ping Wang ◽  
Francesco Petrella ◽  
Luca Nicosia ◽  
Massimo Bellomi ◽  
Stefania Rizzo
Keyword(s):  
Stem Cells ◽  
Stem Cell ◽  
Molecular Imaging ◽  
Stem Cell Transplantation ◽  
Cell Transplantation ◽  
Clinical Studies ◽  
Liver Diseases ◽  
Cell Based Therapy ◽  
Stem Cells Transplantation

Stem cell transplantation has been investigated to rescue experimental liver failure and is promising to offer an alternative therapy to liver transplantation for liver diseases treatment. Several clinical studies in this field have been carried out, but the therapeutic benefit of this treatment is still controversial. A major obstacle to developing stem cell therapies in clinic is being able to visualize the cells in vivo. Imaging modalities allow optimization of delivery, detecting cell survival and functionality by in vivo monitoring these transplanted graft cells. Moreover, theranostic imaging is a brand new field that utilizes nanometer-scale materials to glean diagnostic insight for simultaneous treatment, which is very promising to improve stem cell-based therapy for treatment of liver diseases. The aim of this review was to summarize the various imaging tools that have been explored with advanced molecular imaging probes. We also outline some recent progress of preclinical and clinical studies of liver stem cells transplantation. Finally, we discuss theranostic imaging for stem cells transplantation for liver dysfunction and future opportunities afforded by theranostic imaging.

Human Fetal Liver-Derived Stem Cell Transplantation as Supportive Modality in the Management of End-Stage Decompensated Liver Cirrhosis

2010 ◽  
Vol 19 (4) ◽  
pp. 409-418 ◽  
Author(s):  
Aleem A. Khan ◽  
Mahaboob V. Shaik ◽  
N. Parveen ◽  
A. Rajendraprasad ◽  
Mohammed A. Aleem ◽  
...  
Keyword(s):  
Stem Cells ◽  
Liver Cirrhosis ◽  
Stem Cell ◽  
Stem Cell Transplantation ◽  
Cell Transplantation ◽  
Liver Diseases ◽  
Fetal Liver ◽  
Decompensated Liver Cirrhosis ◽  
Human Fetal Liver ◽  
End Stage

Liver transplantation is the only existing modality for treating decompensated liver cirrhosis. Several factors, such as nonavailability of donors, combined with operative risks, complications associated with rejection, usage of immunosuppressive agents, and cost intensiveness, make this strategy available to only a few people. With a tremendous upsurge in the mortality rate of patients with liver disorders worldwide, there is a need to search for an alternative therapeutic tool that can combat the above limitations and serve as a supportive therapy in the management of liver diseases. Cell therapy using human fetal liver-derived stem cells can provide great potential to conservatively manage end-stage liver diseases. Therefore, the present investigation aimed to study and prove the safety and efficacy of human fetal liver-derived stem cell transplantation in patients with end-stage liver cirrhosis. Twenty-five patients with liver cirrhosis of different etiologies were infused with human fetal liver-derived stem cells (EpCAM+ve) labeled with Tc-HMPAO through hepatic artery. Our high throughput analysis using flow cytometry, RT-PCR, and cellular characterization exemplifies fetal liver cells with their high proliferation rate could be the best source for rejuvenating the diseased liver. Further, no episodes related to hepatic encephalopathy recurred in any of the subjects following hepatic stem cell transplantation. There was marked clinical improvement observed in terms of all clinical and biochemical parameters. Further, there was decrease in mean MELD score ( p < 0.01) observed in 6 months follow-up in all patients. Therapy using human fetal liver stem/progenitor cells offers a potentially supportive modality to organ transplantation in the management of liver diseases.

Stem Cell Transplantation: A Promising Therapy for Spinal Cord Injury

2020 ◽  
Vol 15 (4) ◽  
pp. 321-331 ◽  
Author(s):  
Zhe Gong ◽  
Kaishun Xia ◽  
Ankai Xu ◽  
Chao Yu ◽  
Chenggui Wang ◽  
...  
Keyword(s):  
Spinal Cord ◽  
Stem Cells ◽  
Spinal Cord Injury ◽  
Stem Cell ◽  
Stem Cell Transplantation ◽  
Cell Transplantation ◽  
Therapeutic Potential ◽  
Embryonic Stem ◽  
Current Status ◽  
Cord Injury

Spinal Cord Injury (SCI) causes irreversible functional loss of the affected population. The incidence of SCI keeps increasing, resulting in huge burden on the society. The pathogenesis of SCI involves neuron death and exotic reaction, which could impede neuron regeneration. In clinic, the limited regenerative capacity of endogenous cells after SCI is a major problem. Recent studies have demonstrated that a variety of stem cells such as induced Pluripotent Stem Cells (iPSCs), Embryonic Stem Cells (ESCs), Mesenchymal Stem Cells (MSCs) and Neural Progenitor Cells (NPCs) /Neural Stem Cells (NSCs) have therapeutic potential for SCI. However, the efficacy and safety of these stem cellbased therapy for SCI remain controversial. In this review, we introduce the pathogenesis of SCI, summarize the current status of the application of these stem cells in SCI repair, and discuss possible mechanisms responsible for functional recovery of SCI after stem cell transplantation. Finally, we highlight several areas for further exploitation of stem cells as a promising regenerative therapy of SCI.

Targeting CD96 For Antibody Based Elimination Of Leukemic Stem Cells In AML: A New Strategy In Stem Cell Transplantation

Blood ◽  
2013 ◽  
Vol 122 (21) ◽  
pp. 3972-3972 ◽  
Author(s):  
Matthias Staudinger ◽  
Christian Kellner ◽  
Matthias Peipp ◽  
Natalie Schub ◽  
Andreas Humpe ◽  
...  
Keyword(s):  
Stem Cells ◽  
Flow Cytometry ◽  
Stem Cell ◽  
Stem Cell Transplantation ◽  
Cell Transplantation ◽  
Autologous Stem Cell Transplantation ◽  
Target Cells ◽  
Leukemic Stem Cells ◽  
Hematopoietic Stem

Abstract Although the mortality of autologous stem cell transplantation in contrast to allogeneic is low, in AML patients the lack of immune surveillance as well as contamination of the transplant with residual leukemic stem cells (LSC) limits its use. Therefore, elimination of LSC by targeted therapy may represent a promising therapeutic approach. Recently, CD96 was identified as marker antigen on AML-LSC (Hosen et al., PNAS 104: 11008, 2007). Here, by addressing CD96 with magnetic cell sorting (MACS) or using antibody dependent cellular cytotoxicity (ADCC), new strategies for engineering autologous stem cell grafts or for in vivo targeting of residual AML stem cells are presented. To evaluate the efficacy of depletion of LSC by MACS technology, grafts containing hematopoietic stem cells were spiked with CD96 positive AML cells. Using biotinylated CD96 antibody TH111 raised in our laboratory in combination with anti-biotin-micro beads (Miltenyi Biotech, Bergisch Gladbach, Germany) up to a 1000-fold depletion of targeted cells was achieved. The viability, cell count and the potential of hematopoietic progenitor cells (HPC) to proliferate and differentiate were not affected by this procedure as documented by flow cytometry and colony forming assays. As residual LSC residing within the patient may also account for AML relapse after high-dose chemotherapy and subsequent SCT, eradication of AML stem cells in vivo is desirable. To target CD96+ AML-LSC by ADCC, chimeric antibodies containing wild type or affinity maturated variable regions in combination with an optimized human IgG1Fc were generated by recombinant DNA technologies. Both recombinant antibodies were expressed in Hek 293 cells enriched to homogeneity by affinity chromatography and analyzed for their functional properties. As shown by flow cytometry, the antigen binding affinity of the maturated antibody was enhanced (EC50 0.6 μg/ml vs. 2 μg/ml). Moreover, as analyzed in standard ADCC assays, NK cell mediated lytic properties against CD96-positive target cells were elevated (maximum lysis: 52%) using the affinity maturated chimeric CD96 antibody (EC50: 0.02 μg/ml vs. 0.15 μg/ml). Thus, this CD96 purging strategy avoids unwanted transplantation of AML-LSC and may help to revitalize autologous stem cell transplantation in this indication. Although, specific side effects by CD96 application will have to be considered, this may allow for an additional therapeutic avenue to eliminate in vivo residual AML-LSC in autologous as well as in allogeneic situations. Disclosures: No relevant conflicts of interest to declare.

scholarly journals Hematopoeitic Stem Cells and Their Progenitors Critically Require Autophagy to Promote Early Engraftment Following Allogeneic Stem Cell Transplantation

Blood ◽  
2015 ◽  
Vol 126 (23) ◽  
pp. 34-34
Author(s):  
Katie E Lineburg ◽  
Lucie Leveque-El Mouttie ◽  
Laetitia Le Texier ◽  
Bianca Teal ◽  
Rachel D Kuns ◽  
...  
Keyword(s):  
Stem Cells ◽  
Stem Cell ◽  
Stem Cell Transplantation ◽  
Cell Transplantation ◽  
Graft Failure ◽  
Term Survival ◽  
Hematopoietic Stem ◽  
Post Transplant ◽  
Engraftment Failure ◽  
And Function

Abstract Stem cell transplantation (SCT) is the only curative therapy for the majority of hematological malignancies and relies on successful engraftment of donor hematopoietic stem cells (HSC) to reconstitute the patient's hematopoiesis and immunity. Graft-versus-host disease (GVHD) and graft failure are complications of SCT that contribute to significant morbidity and mortality. Recent studies have established a role for autophagy in the long-term survival and function of HSCs and as a regulator of hematopoiesis. We investigated the contribution of autophagy to HSC in the setting of allogeneic transplantation. Using LC3-GFP bone marrow as a graft source in the well-established B6 into F1 model of GVHD, together with imaging flow cytometry, we demonstrated increased autophagy (LC3-GFP punctae) within donor HSC and progenitor cells in GVHD compared to non-GVHD recipients. To assess the contribution of autophagy to HSC development and function we used mice deficient in Atg5, an essential protein for the autophagy pathway. In primary transplants, ATG5 KO foetal liver (FL) had reduced ability to engraft lethally irradiated congenic recipient mice compared to WT FL. Furthermore, competitive transplantation of 50% ATG5 KO FL cells together with 50% WT FL cells demonstrated that ATG5 KO cells had a reduced capacity to reconstitute compared to congenic WT FL cells. Finally, to address the role of autophagy in HSC in the setting of GVHD, we transplanted WT or ATG5 KO FL ± T cells into lethally irradiated B6D2F1 recipients. At D10 post-transplant ATG5 KO recipients failed to establish tri-lineage engraftment in peripheral blood and lacked expansion of myeloid precursor cells in the BM, leading to engraftment failure and significantly reduced survival compared to WT FL recipients (50% WT vs 10% Atg5 KO p<0.0001). This early engraftment failure was confirmed to be autophagy specific using VAVcre x Atg7fl/fl donor mice, in which Atg7 deficiency is restricted to hematopoietic cells. Furthermore, the essential requirement for autophagy in early progenitors and HSC was confirmed using LysMcre Atg7fl/fl mice, which ablate Atg7 from the granulocyte-macrophage progenitor population onwards. Survival, or engraftment, in mice receiving the LysMcre Atg7fl/fl donor graft did not differ significantly from those receiving a WT graft. We demonstrate that autophagy is increased in the GVHD setting and that without autophagy early myeloid precursors fail to provide short term reconstitution leading to primary graft failure and mortality. Thus, intervention to increase autophagy in these cells post-transplant may improve engraftment in the clinic. Disclosures No relevant conflicts of interest to declare.

scholarly journals Cell-density independent increased lymphocyte production and loss rates post-autologous hematopoietic stem cell transplantation

2020 ◽  
Author(s):  
Mariona Baliu-Piqué ◽  
Vera van Hoeven ◽  
Julia Drylewicz ◽  
Lotte E. van der Wagen ◽  
Anke Janssen ◽  
...  
Keyword(s):  
Stem Cell ◽  
Hematopoietic Stem Cell Transplantation ◽  
Stem Cell Transplantation ◽  
Cell Transplantation ◽  
Hematopoietic Stem Cell ◽  
Survival Rates ◽  
Production Rates ◽  
Hematopoietic Stem ◽  
Loss Rates

AbstractLymphocyte numbers need to be quite tightly regulated. It is generally assumed that lymphocyte production and survival rates increase homeostatically when lymphocyte numbers decrease. This widely-accepted concept is largely based on experiments in mice. In humans, lymphocyte reconstitution usually occurs very slowly, which challenges the idea that density dependent homeostasis aids recovery from lymphopenia. Using in vivo deuterium labelling, we quantified lymphocyte production and survival rates in patients who underwent an autologous hematopoietic stem cell transplantation (autoHSCT). We indeed found that the production rates of most T-cell and B-cell subsets in autoHSCT-patients were 2 to 8-times higher than in healthy controls. These increased lymphocyte production rates went hand in hand with a 3 to 9-fold increase in cell loss rates, and both rates did not normalize when cell numbers did. This challenges the concept of homeostatic regulation of lymphocyte production and survival rates in humans.

scholarly journals Dynamical Simulation of Effective Stem Cell Transplantation for Modulation of Microglia Responses in Stroke Treatment

Symmetry ◽  
2021 ◽  
Vol 13 (3) ◽  
pp. 404
Author(s):  
Awatif Jahman Alqarni ◽  
Azmin Sham Rambely ◽  
Ishak Hashim
Keyword(s):  
Mathematical Model ◽  
Stem Cells ◽  
Stem Cell ◽  
Stem Cell Transplantation ◽  
Cell Transplantation ◽  
Biological Information ◽  
Stroke Treatment ◽  
Early Stages ◽  
The Brain

Stem cell transplantation therapy may inhibit inflammation during stroke and increase the presence of healthy cells in the brain. The novelty of this work, is to introduce a new mathematical model of stem cells transplanted to treat stroke. This manuscript studies the stability of the mathematical model by using the current biological information on stem cell therapy as a possible treatment for inflammation from microglia during stroke. The model is proposed to represent the dynamics of various immune brain cells (resting microglia, pro-inflammation microglia, and anti-inflammation microglia), brain tissue damage and stem cells transplanted. This model is based on a set of five ordinary differential equations and explores the beneficial effects of stem cells transplanted at early stages of inflammation during stroke. The Runge–Kutta method is used to discuss the model analytically and solve it numerically. The results of our simulations are qualitatively consistent with those observed in experiments in vivo, suggesting that the transplanted stem cells could contribute to the increase in the rate of ant-inflammatory microglia and decrease the damage from pro-inflammatory microglia. It is found from the analysis and simulation results that stem cell transplantation can help stroke patients by modulation of the immune response during a stroke and decrease the damage on the brain. In conclusion, this approach may increase the contributions of stem cells transplanted during inflammation therapy in stroke and help to study various therapeutic strategies for stem cells to reduce stroke damage at the early stages.

scholarly journals 193 Does Stem Cell Therapy Hold Promise In The Management Of Traumatic Brain Injuries? A Literature Review of Animal Studies

Neurosurgery ◽  
2017 ◽  
Vol 64 (CN_suppl_1) ◽  
pp. 251-251
Author(s):  
Ayaz M Khawaja ◽  
Maira Mirza ◽  
Gabriel Rodriguez ◽  
Hassan Aziz
Keyword(s):  
Traumatic Brain Injury ◽  
Stem Cells ◽  
Stem Cell ◽  
Brain Injury ◽  
Animal Models ◽  
Literature Review ◽  
Stem Cell Transplantation ◽  
Cell Transplantation ◽  
Animal Studies

Abstract INTRODUCTION There are no neuroprotective and neuroregenerative treatments available for Traumatic Brain Injury (TBI). Clinical trials investigating potential treatments such as therapeutic hypothermia and progesterone have failed. Pre-clinical studies indicate there may be a role of stem-cells in promoting neuroprotection/neuroregeneration in-vivo in animal models of TBI. We aim to provide a pre-clinical literature review into stem-cells as a potential therapeutic option in TBI-animal models. METHODS Using the terms “traumatic brain injury”, “stem-cell”, “preclinical”, and “animal studies”, a literature search was conducted on Pubmed and Google Scholar. Studies were included if there was an in-vivo animal model of TBI with either intravenous or intra-cortical stem-cell transplantation, along-with a control group, and investigated either motor or behavioral outcomes, or a combination. RESULTS >Twenty-seven studies (n = 1184 animals) satisfied the criteria. 774/1184 (65.4%) animals were investigated for outcomes. 17 studies harvested stem-cells from human-source, whereas 10 harvested stem-cells from animal-source. Bone-marrow stromal-cells (BMSC) were used in 17 studies, neural stem-cells (NSC) in 7, and miscellaneous in 3. 450/774 (58.1%) animals received any stem-cell transplantation, whereas 324 were controls. Of animals receiving stem-cell transplantation (450), 339 (75.3%) showed significantly better outcomes relative to control animals in each individual study, with exception of one study. Amongst transplanted animals, functional outcomes did not differ significantly when grouped by stem-cell type (P = 0.553), transplantation route (P = 0.054), and source (P = 0.784). Animals were followed-up until 1 week (n = 5 studies), 2 weeks (n = 10), 4 weeks (n = 5), or >4-weeks (n = 7). CONCLUSION This pre-clinical data demonstrates that stem-cell transplantation may have treatment potential in TBI as shown by improvement in functional outcome in as many as three-quarters of all animals that were treated with stem-cells. This data provides a foundation for the design of clinical translational studies.

scholarly journals A murine model demonstrating reversal of structural and functional correlates of cirrhosis with progenitor cell transplantation

2019 ◽  
Vol 9 (1) ◽  
Author(s):  
Mark D. Muthiah ◽  
Daniel Q. Huang ◽  
Lei Zhou ◽  
Nur Halisah Jumat ◽  
Mahesh Choolani ◽  
...  
Keyword(s):  
Liver Cirrhosis ◽  
Stem Cell ◽  
Liver Disease ◽  
Stem Cell Transplantation ◽  
Cell Transplantation ◽  
Murine Model ◽  
Fetal Liver ◽  
Decompensated Liver Disease ◽  
Human Fetal Liver

Abstract Development of cell transplantation for treating liver cirrhosis hinges critically on the availability of animal models for studying human stem cell transplantation. We report an immune-permissive murine model of liver cirrhosis with full clinical correlates of decompensated liver disease, and allows testing efficacy of stem cell transplantation. Liver cirrhosis was induced in Nod-scid gamma(NSG) mice with oral thioacetamide(TA) and compared to controls over 12 months. 4 month TA treated cirrhotic mice were then transplanted intrasplenically with 2million human fetal liver progenitor cells(HFH) and compared with cirrhotic controls 2 months after transplantation. NSG-TA mice developed shrunken and nodular livers with histological evidence of fibrosis as compared to controls. This was associated with evidence of worsening decompensated liver disease, with jaundice, hypoalbuminemia, coagulopathy, and encephalopathy in NSG-TA mice. Transplantation of HFH resulted in improvement in both fibrosis and markers of decompensated liver disease. We have demonstrated that NSG-TA mice can recapitulate the full clinical picture of structural and functional cirrhosis, both of which can be improved by transplantation of human fetal liver cells. This model serves as a valuable tool for validation of in vivo liver stem cell transplantation and opens up opportunities for studying the mechanism how stem cells reverse fibrosis.

Intravascular cell replacement therapy for stroke

2008 ◽  
Vol 24 (3-4) ◽  
pp. E15 ◽  
Author(s):  
Raphael Guzman ◽  
Raymond Choi ◽  
Atul Gera ◽  
Alejandro De Los Angeles ◽  
Robert H. Andres ◽  
...  
Keyword(s):  
Stem Cells ◽  
Stem Cell ◽  
Stem Cell Transplantation ◽  
Cell Transplantation ◽  
Neural Plasticity ◽  
Novel Therapy ◽  
Stroke Treatment ◽  
Intracerebral Transplantation ◽  
Review Current

✓ The use of stem cell transplantation to restore neurological function after stroke is being recognized as a potential novel therapy. Before stem cell transplantation can become widely applicable, however, questions remain about the optimal site of delivery and timing of transplantation. In particular, there seems to be increasing evidence that intravascular cell delivery after stroke is a viable alternative to intracerebral transplantation. In this review, the authors focus on the intravascular delivery of stem cells for stroke treatment with an emphasis on timing, transendothelial migration and possible mechanisms leading to neuroprotection, angiogenesis, immunomodulation, and neural plasticity. They also review current concepts of in vivo imaging and tracking of stem cells after stroke.

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