Second bone marrow transplantation into regenerating hematopoiesis enhances reconstitution of immune system.

In bone marrow transplantation (BMT), hematopoiesis-reconstituting cells are introduced following myeloablative treatment, which eradicates existing hematopoietic cells and disrupts stroma within the hematopoietic tissue. Both hematopoietic cells and stroma then undergo regeneration. Our study compares the outcomes of a second BMT administered to mice shortly after myeloablative treatment and the first BMT, with those of a second BMT administered to mice experiencing robust hematopoietic regeneration after the initial transplant.

The Effect of Vascular Endothelial Growth Factor C and Adipose-Derived Stem Cells on Lymphatic Regeneration in a Rat Vascularized Lymph Node Transfer Model.

Background:  Lymphedema is a chronic condition characterized by progressive edema with complicated treatment. Recently, new treatment strategies inducing lymphangiogenesis were proposed. The aim of our study was to examine the effect of vascular endothelial growth factor C (VEGF-C) and adipose-derived stem cells (ADSCs) on lymphatic regeneration and drainage re-establishment in vascularized lymph node transfer (VLNT) model using a pedicled vascularized lymph node (VLN) groin flap.

Hematopoiesis Remains Permissive to Bone Marrow Transplantation After Expansion of Progenitors and Resumption of Blood Cell Production.

The immense regenerative power of hematopoietic tissue stems from the activation of the immature stem cells and the progenitor cells. After partial damage, hematopoiesis is reconstituted through a period of intense regeneration when blood cell production originates from erythro-myeloid progenitors in the virtual absence of stem cells. Since the damaged hematopoiesis can also be reconstituted from transplanted hematopoietic cells, we asked whether this also leads to the transient state when activated progenitors initially execute blood cell production.

pH-responsive polymersome-mediated delivery of doxorubicin into tumor sites enhances the therapeutic efficacy and reduces cardiotoxic effects.

The delivery of therapeutics into sites of action by using cargo-delivery platforms potentially minimizes their premature degradation and fast clearance from the bloodstream. Additionally, drug-loaded stimuli-responsive supramolecular assemblies can be produced to respond to the inherent features of tumor microenvironments, such as extracellular acidosis. We report in this framework the use of pH-responsive polymersomes (PSs) manufactured using poly([N-(2-hydroxypropyl)] methacrylamide)-b-poly[2-(diisopropylamino)ethyl methacrylate] as the building unit (PHPMA-b-PDPA).

Chelating Polymers for Hereditary Hemochromatosis Treatment.

Hemochromatosis (iron overload) encompasses a group of diseases that are characterized by a toxic hyperaccumulation of iron in parenchymal organs. Currently, only few treatments for this disease have been approved; however, all these treatments possess severe side effects. In this study, a paradigm for hemochromatosis maintenance/preventive therapy is investigated: polymers with negligible systemic biological availability form stable complexes with iron ions in the gastrointestinal tract, which reduces the biological availability of iron.

Altered Erythro-Myeloid Progenitor Cells Are Highly Expanded in Intensively Regenerating Hematopoiesis.

Regeneration of severely damaged adult tissues is currently only partially understood. Hematopoietic tissue provides a unique opportunity to study tissue regeneration due to its well established steady-state structure and function, easy accessibility, well established research methods, and the well-defined embryonic, fetal, and adult stages of development. Embryonic/fetal liver hematopoiesis and adult hematopoiesis recovering from damage share the need to expand populations of progenitors and stem cells in parallel with increasing production of mature blood cells.

Reactive Oxygen Species (ROS)-Responsive Polymersomes with Site-Specific Chemotherapeutic Delivery into Tumors via Spacer Design Chemistry.

The lack of cellular and tissue specificities in conventional chemotherapies along with the generation of a complex tumor microenvironment (TME) limits the dosage of active agents that reaches tumor sites, thereby resulting in ineffective responses and side effects. Therefore, the development of selective TME-responsive nanomedicines is of due relevance toward successful chemotherapies, albeit challenging. In this framework, we have synthesized novel, ready-to-use ROS-responsive amphiphilic block copolymers (BCs) with two different spacer chemistry designs to connect a hydrophobic boronic ester-based ROS sensor to the polymer backbone.

Cell Cycle Analysis Using In Vivo Staining of DNA-Synthesizing Cells.

The thymidine analogues BrdU (5-bromo-2´-deoxyuridine) and EdU (5-ethynyl-2´-deoxyuridine) are routinely used for determination of the cells synthesizing DNA in the S-phase of the cell cycle. Availability of the anti-BrdU antibody clone MoBu-1 detecting only BrdU allowed to develop a method for the sequential DNA labelling by these two thymidine analogues for determining the cell cycle kinetic parameters.In the current step-by-step protocol, we present` two approaches optimized for in vivo study of the cell cycle and the limitations that such approaches imply: (1) determination of the cell flow rate into the G2-phase by dual EdU/BrdU DNA-labelling method and (2) determination of the outflow of DNA-labelled cells arising from the mitosis.

Cell cycle and differentiation of Sca-1 and Sca-1 hematopoietic stem and progenitor cells.

Hematopoietic stem and progenitor cells (HSPCs) are crucial for lifelong blood cell production. We analyzed the cell cycle and cell production rate in HSPCs in murine hematopoiesis. The labeling of DNA-synthesizing cells by two thymidine analogues, optimized for in-vivo use, enabled determination of the cell cycle flow rate into G2-phase, the duration of S-phase and the average cell cycle time in Sca-1 and Sca-1 HSPCs.

Stem Cell Defect in Ubiquitin-Green Fluorescent Protein Mice Facilitates Engraftment of Lymphoid-Primed Hematopoietic Stem Cells.

Transgenic mice expressing green fluorescent protein (GFP) are useful in transplantation experiments. When we used ubiquitin-GFP (UBC-GFP) transgenic mice to study the availability of niches for transplanted hematopoietic stem and progenitor cells, the results were strikingly different from the corresponding experiments that used congenic mice polymorphic in the CD45 antigen. Analysis of these unexpected results revealed that the hematopoiesis of UBC-GFP mice was outcompeted by the hematopoiesis of wild-type (WT) mice.

Thermoresponsive β-glucan-based polymers for bimodal immunoradiotherapy - Are they able to promote the immune system?

A conceptually new bimodal immunoradiotherapy treatment was demonstrated using thermoresponsive polymer β-glucan-graft-poly(2-isopropyl-2-oxazoline-co-2-butyl-2-oxazoline) bearing complexes of 1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid with yttrium-90(III) at the graft ends. The behavior of this thermoresponsive polymer in aqueous solutions was studied, and it showed the appropriate cloud point temperature for brachytherapy applications. The polymer was tested in vitro, and it exhibited nontoxicity and active uptake into cancer cells and macrophages with colocalization in the lysosomes and macrophagosomes.

The pharmacological activation of adenosine A1 and A 3 receptors does not modulate the long- or short-term repopulating ability of hematopoietic stem and multipotent progenitor cells in mice.

This study continues our earlier findings on the hematopoiesis-modulating effects of adenosine A1 and A3 receptor agonists that were performed on committed hematopoietic progenitor and precursor cell populations. In the earlier experiments, N (6)-cyclopentyladenosine (CPA), an adenosine A1 receptor agonist, was found to inhibit proliferation in the above-mentioned hematopoietic cell systems, whereas N (6)-(3-iodobenzyl)adenosine-5'-N-methyluronamide (IB-MECA), an adenosine A3 receptor agonist, was found to stimulate it. The topic of this study was to evaluate the possibility that the above-mentioned adenosine receptor agonists modulate the behavior of early hematopoietic progenitor cells and hematopoietic stem cells.

Effects of endostatin production on oncogenicity and metastatic activity of HPV16-transformed mouse cells: role of interleukin 1alpha.

Two mouse HPV16-transformed cell lines, viz. MK16 cells, which induce metastasizing tumors, and TC-1 cells, which induce non-metastasizing tumors were transduced with the gene for mouse endostatin. Two clones constitutively expressing endostatin were isolated from each of them.