scholarly journals Defining Molecular Phenotypes of Mesenchymal and hematopoietic Stem Cells derived from Peripheral blood of Acute Lymphocytic Leukemia patients for regenerative stem cell therapy

2011 ◽  
Vol 7 (1) ◽  
pp. 29-40 ◽  
Keyword(s):  
Stem Cells ◽  
Stem Cell ◽  
Cell Therapy ◽  
Hematopoietic Stem Cells ◽  
Stem Cell Therapy ◽  
Peripheral Blood ◽  
Acute Lymphocytic Leukemia ◽  
Lymphocytic Leukemia ◽  
Hematopoietic Stem ◽  
Molecular Phenotypes

scholarly journals Intestinal myofibroblasts: targets for stem cell therapy

2011 ◽  
Vol 300 (5) ◽  
pp. G684-G696 ◽  
Author(s):  
R. C. Mifflin ◽  
I. V. Pinchuk ◽  
J. I. Saada ◽  
D. W. Powell
Keyword(s):  
Stem Cells ◽  
Smooth Muscle ◽  
Stem Cell ◽  
Cell Therapy ◽  
Lamina Propria ◽  
Stem Cell Therapy ◽  
Intestinal Inflammation ◽  
Mesenchymal Cells ◽  
Hematopoietic Stem ◽  
Intestinal Lamina Propria

The subepithelial intestinal myofibroblast is an important cell orchestrating many diverse functions in the intestine and is involved in growth and repair, tumorigenesis, inflammation, and fibrosis. The myofibroblast is but one of several α-smooth muscle actin-positive (α-SMA+) mesenchymal cells present within the intestinal lamina propria, including vascular pericytes, bone marrow-derived stem cells (mesenchymal stem cells or hematopoietic stem cells), muscularis mucosae, and the lymphatic pericytes (colon) and organized smooth muscle (small intestine) associated with the lymphatic lacteals. These other mesenchymal cells perform many of the functions previously attributed to subepithelial myofibroblasts. This review discusses the definition of a myofibroblast and reconsiders whether the α-SMA+ subepithelial cells in the intestine are myofibroblasts or other types of mesenchymal cells, i.e., pericytes. Current information about specific, or not so specific, molecular markers of lamina propria mesenchymal cells is reviewed, as well as the origins of intestinal myofibroblasts and pericytes in the intestinal lamina propria and their replenishment after injury. Current concepts and research on stem cell therapy for intestinal inflammation are summarized. Information about the stem cell origin of intestinal stromal cells may inform future stem cell therapies to treat human inflammatory bowel disease (IBD).

scholarly journals Efficient retrovirus transduction of mouse pluripotent hematopoietic stem cells mobilized into the peripheral blood by treatment with granulocyte colony-stimulating factor and stem cell factor

Blood ◽  
1994 ◽  
Vol 84 (5) ◽  
pp. 1482-1491 ◽  
Author(s):  
DM Bodine ◽  
NE Seidel ◽  
MS Gale ◽  
AW Nienhuis ◽  
D Orlic
Keyword(s):  
Stem Cells ◽  
Stem Cell ◽  
Gene Transfer ◽  
Hematopoietic Stem Cells ◽  
Peripheral Blood ◽  
Stem Cell Factor ◽  
Granulocyte Colony Stimulating Factor ◽  
Colony Stimulating Factor ◽  
Hematopoietic Stem ◽  
Stimulating Factor

Abstract Cytokine-mobilized peripheral blood cells have been shown to participate in hematopoietic recovery after bone marrow (BM) transplantation, and are proposed to be useful targets for retrovirus- mediated gene transfer protocols. We treated mice with granulocyte colony-stimulating factor (G-CSF) and stem cell factor (SCF) to mobilize hematopoietic progenitor cells into the peripheral blood. These cells were analyzed for the number and frequency of pluripotent hematopoietic stem cells (PHSC). We found that splenectomized animals treated for 5 days with G-CSF and SCF showed a threefold increase in the absolute number of PHSC over normal mice. The number of peripheral- blood PHSC increased 250-fold from 29 per untreated mouse to 7,200 in peripheral-blood PHSC in splenectomized animals treated for 5 days with G-CSF and SCF. Peripheral blood PHSC mobilized by treatment with G-CSF and SCF were analyzed for their ability to be transduced by retroviral vectors. Peripheral-blood PHSC from splenectomized animals G-CSF and SCF were transduced with a recombinant retrovirus containing the human MDR-1 gene. The frequency of gene transfer into peripheral blood PHSC from animals treated for 5 and 7 days was two-fold and threefold higher than gene transfer into PHSC from the BM of 5-fluorouracil-treated mice (P < .01). We conclude that peripheral blood stem cells mobilized by treatment with G-CSF and SCF are excellent targets for retrovirus- mediated gene transfer.

Multifunctional Role of Caspase-3 in Regulating Hematopoietic Stem Cells.

Blood ◽  
2006 ◽  
Vol 108 (11) ◽  
pp. 861-861 ◽  
Author(s):  
Viktor Janzen ◽  
Heather E. Fleming ◽  
Michael T. Waring ◽  
Craig D. Milne ◽  
David T. Scadden
Keyword(s):  
Cell Cycle ◽  
Stem Cells ◽  
Bone Marrow ◽  
Stem Cell ◽  
Hematopoietic Stem Cells ◽  
Peripheral Blood ◽  
Caspase 3 ◽  
Brdu Incorporation ◽  
Hematopoietic Stem ◽  
Regulatory Pathways

Abstract The processes of cell cycle control, differentiation and apoptosis are closely intertwined in controlling cell fate during development and in adult homeostasis. Molecular pathways connecting these events in stem cells are poorly defined and we were particularly interested in the cysteine-aspartic acid protease, Caspase-3, an ‘executioner’ caspase also implicated in the regulation of the cyclin dependent kinase inhibitors, p21Cip1 and p27Kip1. These latter proteins are known to participate in primitive hematopoietic cell cycling and self-renewal. We demonstrated high levels of Caspase-3 mRNA and protein in immunophenotypically defined mouse hematopoietic stem cells (HSC). Using mice engineered to be deficient in Caspase-3, we observed a consistent reduction of lymphocytes in peripheral blood counts and a slight reduction in bone marrow cellularity. Notably, knockout animals had an increase in the stem cell enriched Lin−cKit+Sca1+Flk2low (LKSFlk2lo) cell fraction. The apoptotic rates of LKS cells under homeostatic conditions as assayed by the Annexin V assay were not significantly different from controls. However, in-vitro analysis of sorted LKS cells revealed a reduced sensitivity to apoptotic cell death in absence of Caspase-3 under conditions of stress (cytokine withdrawal or gamma irradiation). Primitive hematopoietic cells displayed a higher proliferation rate as demonstrated by BrdU incorporation and a significant reduction in the percentage of cells in the quiescent stage of the cell cycle assessed by the Pyronin-Y/Hoechst staining. Upon transplantation, Caspase-3−/− stem cells demonstrated marked differentiation abnormalities with significantly reduced ability to differentiate into multiple hematopoietic lineages while maintaining an increased number of primitive cells. In a competitive bone marrow transplant using congenic mouse stains Capase-3 deficient HSC out-competed WT cells at the stem cell level, while giving rise to comparable number of peripheral blood cells as the WT controls. Transplant of WT BM cells into Caspase-3 deficient mice revealed no difference in reconstitution ability, suggesting negligible effect of the Caspase-3−/− niche microenvironment to stem cell function. These data indicate that Caspase-3 is involved in the regulation of differentiation and proliferation of HSC as a cell autonomous process. The molecular bases for these effects remain to be determined, but the multi-faceted nature of the changes seen suggest that Caspase-3 is central to multiple regulatory pathways in the stem cell compartment.

Stem Cell Therapy for Articular Cartilage Repair: Review of the Entity of Cell Populations Used and the Result of the Clinical Application of Each Entity

2017 ◽  
Vol 46 (10) ◽  
pp. 2540-2552 ◽  
Author(s):  
Yong-Beom Park ◽  
Chul-Won Ha ◽  
Ji Heon Rhim ◽  
Han-Jun Lee
Keyword(s):  
Stem Cells ◽  
Bone Marrow ◽  
Adipose Tissue ◽  
Stem Cell ◽  
Articular Cartilage ◽  
Cell Therapy ◽  
Cartilage Repair ◽  
Stem Cell Therapy ◽  
Peripheral Blood ◽  
Cell Populations

Background: Following successful preclinical studies, stem cell therapy is emerging as a candidate for the treatment of articular cartilage lesions. Because stem cell therapy for cartilage repair in humans is at an early phase, confusion and errors are found in the literature regarding use of the term stem cell therapy in this field. Purpose: To provide an overview of the outcomes of cartilage repair, elucidating the various cell populations used, and thus reduce confusion with regard to using the term stem cell therapy. Study Design: Systematic review. Methods: The authors systematically reviewed any studies on clinical application of mesenchymal stem cells (MSCs) in human subjects. A comprehensive search was performed in MEDLINE, EMBASE, the Cochrane Library, CINAHL, Web of Science, and Scopus for human studies that evaluated articular cartilage repair with cell populations containing MSCs. These studies were classified as using bone marrow–derived MSCs, adipose tissue–derived MSCs, peripheral blood–derived MSCs, synovium-derived MSCs, and umbilical cord blood–derived MSCs according to the entity of cell population used. Results: Forty-six clinical studies were identified to focus on cartilage repair with MSCs: 20 studies with bone marrow–derived MSCs, 21 studies with adipose tissue–derived MSCs, 3 studies with peripheral blood–derived MSCs, 1 study with synovium-derived MSCs, and 1 study with umbilical cord blood–derived MSCs. All clinical studies reported that cartilage treated with MSCs showed favorable clinical outcomes in terms of clinical scores or cartilage repair evaluated by MRI. However, most studies were limited to case reports and case series. Among these 46 clinical studies, 18 studies erroneously referred to adipose tissue–derived stromal vascular fractions as “adipose-derived MSCs,” 2 studies referred to peripheral blood–derived progenitor cells as “peripheral blood–derived MSCs,” and 1 study referred to bone marrow aspirate concentrate as “bone marrow–derived MSCs.” Conclusion: Limited evidence is available regarding clinical benefit of stem cell therapy for articular cartilage repair. Because the literature contains substantial errors in describing the therapeutic cells used, researchers need to be alert and observant of proper terms, especially regarding whether the cells used were stem cells or cell populations containing a small portion of stem cells, to prevent confusion in understanding the results of a given stem cell–based therapy.

scholarly journals Stem Cell Therapy in Treating Type 1 Diabetes Mellitus –Potential and Ethical Issues.

2021 ◽  
Author(s):  
Nursuaidah Abdullah ◽  
Marjanu Hikmah Elias
Keyword(s):  
Stem Cells ◽  
Type 1 Diabetes ◽  
Stem Cell ◽  
Cell Therapy ◽  
Stem Cell Therapy ◽  
Cell Transplant ◽  
Exogenous Insulin ◽  
Hematopoietic Stem ◽  
Wide Range

Type 1 diabetes (T1D) is a deficiency in insulin production which is mainly due to loss of ?-cell pancreatic islets. Patients with T1D need to be given exogenous insulin regularly. While improvements in the delivery of insulin and glucose monitoring methods have been effective in improving patient safety, insulin therapy is not a cure and is often associated with complications and debilitating hypoglycaemic episodes. Meanwhile, pancreas or islet transplantation as a gold standard only promises temporary freedom from exogenous insulin and suffers from issues of its own. Stem cell therapy may provide a more permanent solution, given stem cells’ immunomodulatory characteristics and ability to self-renew and distinguish into specific cells. In this sense, the therapeutic potentials of stem cells are addressed in this study. These stem cells cover a wide range of treatments for T1D including embryonic stem cells, induced pluripotent stem cells, bone-marrow derived hematopoietic stem cells and multipotent mesenchymal stromal cells. The challenges faced by the current stem cell transplant in T1D treatment and Islamic viewpoints regarding ethics in stem cell research and therapy are also discussed. In conclusion, stem cell therapy offers a safe and efficient alternative treatment for T1D. However, besides the fatwa from Fatwa Committee of Selangor, the lack of Malaysian stem cells ethics should be further addressed.

scholarly journals Efficient retrovirus transduction of mouse pluripotent hematopoietic stem cells mobilized into the peripheral blood by treatment with granulocyte colony-stimulating factor and stem cell factor

Blood ◽  
1994 ◽  
Vol 84 (5) ◽  
pp. 1482-1491 ◽  
Author(s):  
DM Bodine ◽  
NE Seidel ◽  
MS Gale ◽  
AW Nienhuis ◽  
D Orlic
Keyword(s):  
Stem Cells ◽  
Stem Cell ◽  
Gene Transfer ◽  
Hematopoietic Stem Cells ◽  
Peripheral Blood ◽  
Stem Cell Factor ◽  
Granulocyte Colony Stimulating Factor ◽  
Colony Stimulating Factor ◽  
Hematopoietic Stem ◽  
Stimulating Factor

Cytokine-mobilized peripheral blood cells have been shown to participate in hematopoietic recovery after bone marrow (BM) transplantation, and are proposed to be useful targets for retrovirus- mediated gene transfer protocols. We treated mice with granulocyte colony-stimulating factor (G-CSF) and stem cell factor (SCF) to mobilize hematopoietic progenitor cells into the peripheral blood. These cells were analyzed for the number and frequency of pluripotent hematopoietic stem cells (PHSC). We found that splenectomized animals treated for 5 days with G-CSF and SCF showed a threefold increase in the absolute number of PHSC over normal mice. The number of peripheral- blood PHSC increased 250-fold from 29 per untreated mouse to 7,200 in peripheral-blood PHSC in splenectomized animals treated for 5 days with G-CSF and SCF. Peripheral blood PHSC mobilized by treatment with G-CSF and SCF were analyzed for their ability to be transduced by retroviral vectors. Peripheral-blood PHSC from splenectomized animals G-CSF and SCF were transduced with a recombinant retrovirus containing the human MDR-1 gene. The frequency of gene transfer into peripheral blood PHSC from animals treated for 5 and 7 days was two-fold and threefold higher than gene transfer into PHSC from the BM of 5-fluorouracil-treated mice (P < .01). We conclude that peripheral blood stem cells mobilized by treatment with G-CSF and SCF are excellent targets for retrovirus- mediated gene transfer.

Outpatient Decitabine in Elderly Patients with Acute Myeloid Leukemia (AML).

Blood ◽  
2009 ◽  
Vol 114 (22) ◽  
pp. 4144-4144 ◽  
Author(s):  
Alexey V. Danilov ◽  
Hedy Smith ◽  
Valerie Relias ◽  
Kenneth B Miller
Keyword(s):  
Stem Cells ◽  
Overall Survival ◽  
Stem Cell ◽  
High Risk ◽  
Cell Therapy ◽  
Elderly Patients ◽  
Treatment Option ◽  
Stem Cell Therapy ◽  
Peripheral Blood ◽  
Risk Patients

Abstract Abstract 4144 Background The treatment of elderly patients with AML remains controversial due to the inferiority of outcomes associated with standard intensive induction regimens. Hypomethylating agents have been shown to improve quality of life and survival in patients with myelodysplastic syndromes and have activity in AML. We report our experience with decitabine in elderly patients with previously untreated or refractory AML. Patients and methods We conducted a retrospective analysis of 30 patients (11 males and 19 females) with AML who were ineligible for intensive induction chemotherapy and received decitabine (20 mg/m2 for 5 days every 28 days). Median age at diagnosis was 67 years (range 40 to 91 years), 28/30 (93.3%) patients were 60 years of age or older. Twelve (40%) patients had cytogenetic abnormalities (7 – unfavorable). ECOG performance status was 0-1 for 26 patients, 2 for 3 patients and 3 for 1 patient. Seven (23.3%) patients had secondary AML and 23 (76.7%) patients had de novo AML, of which 10 demonstrated evidence of multilineage dysplasia on bone marrow biopsy. Eleven (36.7%) patients progressed after prior therapy which included intensive induction therapy in 10 patients (followed by stem cell therapy in 4 patients) and tipifarnib in 1 patient. Nineteen (63.3%) patients received decitabine as first-line therapy. Clearance of blasts from the peripheral blood was monitored and used as an indicator of improved relapse-free survival in AML. Overall survival was defined as the time from the day 1 of decitabine treatment to death. Results Patients received a median of 5 cycles of decitabine. Seven patients (23.3%) received ≥10 cycles. All patients received decitabine in the outpatient setting. No hospitalizations were required to administer treatment. Peripheral blood blast clearance was documented in 23 (76.7%) patients including 7 patients who achieved a CR/CRi, and 2 PR. The median time to response was 2 months with median duration of 3 months. Seven patients (23.3%) did not respond to treatment. To date, 19 (63.3%) patients have died after 5-24 months of therapy and 11 (36.7%) remain alive. The median survival was 12 months in all patients (range 4 to 24 months) and 14 months in the 17 patients who received more than 4 cycles of therapy. Overall survival was 82.4% at 6 months and 47.9% at 12 months. Eleven (36.7%) patients survived for >1 year. Seven patients underwent allogeneic stem cell therapy after achieving CR/CRi on decitabine. Three patients received stem cells from siblings or offspring; 3 patients had a matched unrelated donor and 1 patient received umbilical cord stem cells. Three patients are alive after a median follow-up of 12 months. Three patients died of relapsed AML and 1 patient died of infectious complications of transplant. Decitabine was well tolerated. Ten patients experienced minimal nausea amenable to ondansetron with no documented episodes of vomiting. Seventeen patients developed grade 4 neutropenia and 3 patients grade 4 thrombocytopenia during the course of treatment. Fourteen (46.7%) patients underwent a total of 37 hospitalizations. Common reasons for hospitalizations were: febrile neutropenia (19), pneumonia (6) and thrombocytopenia (3). Sixteen (53.3%) patients never required hospitalization while undergoing treatment. No deaths were attributed to complications related to therapy. Decitabine administered as an outpatient is an effective treatment option for elderly and high risk patients with AML. It has a favorable chemotherapy-related toxicity profile and is associated with a decreased frequency of hospitalizations. Decitabine may facilitate a subsequent allogeneic transplant in eligible patients and should be considered a treatment option for high risk patients with AML. Disclosures: Off Label Use: decitabine in AML.

scholarly journals Dnmt3a loss predisposes murine hematopoietic stem cells to malignant transformation

Blood ◽  
2015 ◽  
Vol 125 (4) ◽  
pp. 629-638 ◽  
Author(s):  
Allison Mayle ◽  
Liubin Yang ◽  
Benjamin Rodriguez ◽  
Ting Zhou ◽  
Edmund Chang ◽  
...  
Keyword(s):  
Stem Cells ◽  
T Cell ◽  
Hematopoietic Stem Cells ◽  
Malignant Transformation ◽  
Acute Lymphocytic Leukemia ◽  
Lymphocytic Leukemia ◽  
Hematopoietic Stem ◽  
Myeloid Malignancies ◽  
Lymphoid Malignancies ◽  
Key Points

Key Points Dnmt3a ablation in HSCs predisposes mice to develop a spectrum of myeloid and lymphoid malignancies. Dnmt3a-KO-derived myeloid malignancies and T-cell acute lymphocytic leukemia/lymphoma show distinct methylation aberrations.

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