scholarly journals Cell technologies in reproductology, obstetrics and gynecology

2013 ◽  
Vol 1 (1) ◽  
pp. 61-65 ◽  
Author(s):  
C. Nasadyuk
Keyword(s):  
Breast Cancer ◽  
Gene Therapy ◽  
Stem Cell ◽  
Reproductive Medicine ◽  
Obstetrics And Gynecology ◽  
Hematopoietic Stem ◽  
Uterus Transplantation ◽  
Current Trends ◽  
Gene Technologies ◽  
Cell And Gene Therapy

The review describes the current trends of the development of cell and gene technologies in obstetrics, gynecology and reproductive medicine. The strategies of allogeneic and autologous hematopoietic stem cell transplantation in the myeloablative treatment of germinal tumors and breast cancer are considered, as well as adoptive immunotherapy, modern approaches to the treatment of female and male infertility, and also prenatal cell and gene therapy. The problems and achievements in uterus transplantation are described, as well as the successes in the cryopreservation of reproductive cells and tissues.

scholarly journals Hematopoietic Stem Cell and Gene Therapy Corrects Primary Neuropathology and Behavior in Mucopolysaccharidosis IIIA Mice

2012 ◽  
Vol 20 (8) ◽  
pp. 1610-1621 ◽  
Author(s):  
Alexander Langford-Smith ◽  
Fiona L Wilkinson ◽  
Kia J Langford-Smith ◽  
Rebecca J Holley ◽  
Ana Sergijenko ◽  
...  
Keyword(s):  
Gene Therapy ◽  
Stem Cell ◽  
Hematopoietic Stem Cell ◽  
Hematopoietic Stem ◽  
Cell And Gene Therapy ◽  
And Behavior

scholarly journals Toward a stem cell gene therapy for breast cancer

Blood ◽  
2009 ◽  
Vol 113 (22) ◽  
pp. 5423-5433 ◽  
Author(s):  
ZongYi Li ◽  
Ying Liu ◽  
Sebastian Tuve ◽  
Ye Xun ◽  
Xiaolong Fan ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Gene Therapy ◽  
Stem Cell ◽  
Tumor Cells ◽  
Tumor Stroma ◽  
Inflammatory Cells ◽  
Hematopoietic Stem ◽  
Cell Gene ◽  
Stem Cell Gene ◽  
Stem Cell Gene Therapy

Current approaches for treatment of late-stage breast cancer rarely result in a long-term cure. In part this is due to tumor stroma that prevents access of systemically or intratumorally applied therapeutics. We propose a stem cell gene therapy approach for controlled tumor stroma degradation that uses the pathophysiologic process of recruitment of inflammatory cells into the tumor. This approach involves genetic modification of hematopoietic stem cells (HSCs) and their subsequent transplantation into tumor-bearing mice. We show that inducible, intratumoral expression of relaxin (Rlx) either by transplanting tumor cells that contained the Rlx gene or by transplantation of mouse HSCs transduced with an Rlx-expressing lentivirus vector delays tumor growth in a mouse model of breast cancer. The antitumor effect of Rlx was mediated through degradation of tumor stroma, which provided increased access of infiltrating antitumor immune cells to their target tumor cells. Furthermore, we have shown in a human/mouse chimeric model that genetically modified HSCs expressing a transgene can access the tumor site. Our findings are relevant for cancer gene therapy and immunotherapy.

Hematopoietic Stem Cell Expansion, without Exhaustion or Transformation, by Stable Microrna Antagonism in Vivo

Blood ◽  
2012 ◽  
Vol 120 (21) ◽  
pp. 30-30
Author(s):  
Bernhard Gentner ◽  
Alice Giustacchini ◽  
Eric Lechman ◽  
Peter van Galen ◽  
Francesco Boccalatte ◽  
...  
Keyword(s):  
Gene Therapy ◽  
Stem Cell ◽  
Steady State ◽  
Hematopoietic Stem Cell ◽  
Pi3k Pathway ◽  
Cellular Functions ◽  
Hematopoietic Stem ◽  
Cell Counts ◽  
Cell And Gene Therapy

Abstract Abstract 30 The precise mechanisms controlling hematopoietic stem cell (HSC) quiescence, self renewal and differentiation remain incompletely understood, and HSC expansion remains a long sought after goal for cell- and gene therapy. Genetic manipulation of single transcription factors and signal transduction pathways has so far failed to provide sustained HSC expansion, often resulting in stem cell exhaustion or the emergence of malignancy. MicroRNAs (miRNAs) post-transcriptionally regulate multiple genes in a coordinated fashion, making them attractive targets to manipulate signaling networks and complex cellular functions. We have systematically manipulated miR-126, a miRNA enriched in the primitive hematopoietic compartment, in mouse and human HSC by stably knocking down its activity with a sponge lentiviral vector (126/KD LV) or forcing its overexpression by a 126/OE LV. Hematochimeric mice were generated by transplanting 126/OE LV- or 126/KD LV- transduced progenitors into congenic mice (murine HSC) or NSG mice (human HSC), and the effects of altered miR-126 levels on hematopoiesis were investigated in vivo. Steady state hematopoiesis was comparatively normal, with no alterations in complete blood cell counts except a minor skewing towards or against lymphopoiesis upon 126/OE or 126/KD, respectively. Strikingly, under stress conditions such as 5-fluorouracil exposure, secondary transplantation or the NSG xenograft environment, 126/OE resulted in a progressive loss of HSC, while 126/KD increased HSC numbers as measured by immunophenotype and functional output upon competitive transplantation into secondary recipients. Limiting dilution analysis confirmed a 3–4 fold expansion of mouse and human HSC upon miR-126/KD, and the competitive advantage of 126/KD HSC was maintained long-term including post tertiary transplantation. To study the mechanism by which miR-126 regulates HSC numbers, cell cycle analysis was performed on 126/KD- or 126/OE progenitors isolated from steady state bone marrow. Human CD34+CD38-CD90+ and murine Lineage-Kit+Sca+CD150+ HSC were shifted towards the S/G2/M or the G0 phase upon 126/KD or 126/OE, respectively, indicating that miR-126 antagonism increased cycling while excessive levels of miR-126 favoured HSC quiescence within the niche microenvironment. Interestingly, this effect was highly specific for HSC and the most primitive progenitors. An in vitro culture model of HSC-enriched cord blood cells was set up to study the molecular basis of miR-126 mediated control of HSC cycling. This model reproduced key aspects of the HSC phenotype observed in vivo, i.e. increased or decreased proliferation of primitive progenitors upon 126/KD or 126/OE, respectively. Transcriptome analysis indicated that miR-126 manipulation altered several cellular functions and pathways, most significantly the PI3K/AKT/GSK3β signalling axis. We confirmed PIK3R2 and CRKII as direct miR-126 targets in CB CD34+38- cells and show enhanced PI3K pathway activation as reflected by increased AKT and GSK3β phosphorylation upon 126/KD, while 126/OE caused opposite effects. Pharmacologic inhibition of the beta subunit of PI3K abrogated the 126/KD phenotype, indicating that miR-126 mainly acts through the PI3K pathway. In contrast to published studies showing HSC expansion upon hyperactivation of the PI3K pathway using various genetic approaches, miR-126/KD did not cause HSC exhaustion or leukemogenesis. On the contrary, evidence will be provided that 126/OE is oncogenic in hematopoietic cells. Thus, miR-126 represents a principle target for HSC expansion for cell and gene therapy applications. In summary, we propose that in vivo HSC pool size is influenced by endogenous levels of miR-126 through modulation of the HSC quiescence/proliferation equilibrium. Disclosures: No relevant conflicts of interest to declare.

High-dose chemotherapy and hematopoietic stem cell transplantation for breast cancer: Past or future?

2001 ◽  
Vol 28 (4) ◽  
pp. 377-388 ◽  
Author(s):  
Roy D. Baynes ◽  
Roger D. Dansey ◽  
Jared L. Klein ◽  
Caroline Hamm ◽  
Mark Campbell ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Stem Cell ◽  
Hematopoietic Stem Cell Transplantation ◽  
Stem Cell Transplantation ◽  
Cell Transplantation ◽  
Hematopoietic Stem Cell ◽  
High Dose Chemotherapy ◽  
High Dose ◽  
Hematopoietic Stem

Long-term hematopoietic stem cell gene therapy corrects neuromuscular manifestations in preclinical study of Pompe mice

2021 ◽  
Vol 132 (2) ◽  
pp. S107
Author(s):  
Niek P. van Til ◽  
Yildirim Dogan ◽  
Cecilia Barese ◽  
Zeenath Unnisa ◽  
Swaroopa Guda ◽  
...  
Keyword(s):  
Gene Therapy ◽  
Stem Cell ◽  
Hematopoietic Stem Cell ◽  
Preclinical Study ◽  
Hematopoietic Stem ◽  
Cell Gene ◽  
Stem Cell Gene ◽  
Stem Cell Gene Therapy

Fetal stem cell and gene therapy

2017 ◽  
Vol 22 (6) ◽  
pp. 410-414 ◽  
Author(s):  
Russell Witt ◽  
Tippi C. MacKenzie ◽  
William H. Peranteau
Keyword(s):  
Gene Therapy ◽  
Stem Cell ◽  
Fetal Stem Cell ◽  
Cell And Gene Therapy
Sign in / Sign up

Export Citation Format

Share Document