Non-conditioned bone marrow chimeric mouse generation using culture-based enrichment of hematopoietic stem and progenitor cells.

Bone marrow (BM) chimeric mice are a valuable tool in the field of immunology, with the genetic manipulation of donor cells widely used to study gene function under physiological and pathological settings. To date, however, BM chimera protocols require myeloablative conditioning of recipient mice, which dramatically alters steady-state hematopoiesis. Additionally, most protocols use fluorescence-activated cell sorting (FACS) of hematopoietic stem/progenitor cells (HSPCs) for ex vivo genetic manipulation.

Interleukin-12 supports in vitro self-renewal of long-term hematopoietic stem cells.

Hematopoietic stem cells (HSCs) self-renew or differentiate through division. Cytokines are essential for inducing HSC division, but the optimal cytokine combination to control self-renewal of HSC in vitro remains unclear. In this study, we compared the effects of interleukin-12 (IL-12) and thrombopoietin (TPO) in combination with stem cell factor (SCF) on in vitro self-renewal of HSCs.

Author Correction: Long-term ex vivo haematopoietic-stem-cell expansion allows nonconditioned transplantation.

An Amendment to this paper has been published and can be accessed via a link at the top of the paper.

Long-term ex vivo haematopoietic-stem-cell expansion allows nonconditioned transplantation.

Multipotent self-renewing haematopoietic stem cells (HSCs) regenerate the adult blood system after transplantation, which is a curative therapy for numerous diseases including immunodeficiencies and leukaemias. Although substantial effort has been applied to identifying HSC maintenance factors through the characterization of the in vivo bone-marrow HSC microenvironment or niche, stable ex vivo HSC expansion has previously been unattainable. Here we describe the development of a defined, albumin-free culture system that supports the long-term ex vivo expansion of functional mouse HSCs.

Fine-scale geographic clustering pattern of human T-cell leukemia virus type 1 infection among blood donors in Kyushu-Okinawa, Japan.

Human T-cell leukemia virus type I (HTLV-1) infection is endemic in Japan, particularly clustered in the southwestern district, Kyushu-Okinawa, which consists of eight prefectures that further consist of 274 municipalities. However, no information is available about the fine-scale distribution of HTLV-1 infection within Kyushu-Okinawa. To assess the municipal-level distribution of people with HTLV-1 infection in Kyushu-Okinawa, we performed a cross-sectional study using a fine-scale geographic information system map based on HTLV-1 screening test results from the Japanese Red Cross database from September 2012 to February 2014.

Branched-chain amino acid depletion conditions bone marrow for hematopoietic stem cell transplantation avoiding amino acid imbalance-associated toxicity.

Hematopoietic stem cells (HSCs) are used clinically in bone marrow (BM) transplantation due to their unique ability to reform the entire hematopoietic system. Recently, we reported that HSCs are highly sensitive to valine, one of the three branched-chain amino acids (BCAAs) in addition to isoleucine and leucine. Dietary depletion of valine could even be used as a conditioning regimen for HSC transplantation.

Physiological P95H expression causes impaired hematopoietic stem cell functions and aberrant RNA splicing in mice.

Splicing factor mutations are characteristic of myelodysplastic syndromes (MDS) and related myeloid neoplasms and implicated in their pathogenesis, but their roles in the development of MDS have not been fully elucidated. In the present study, we investigated the consequence of mutant expression using newly generated -mediated conditional knockin mice. Mice carrying a heterozygous P95H mutation showed significantly reduced numbers of hematopoietic stem and progenitor cells (HSPCs) and differentiation defects both in the steady-state condition and transplantation settings.

Analysis of HTLV-1 proviral load (PVL) and antibody detected with various kinds of tests in Japanese blood donors to understand the relationship between PVL and antibody level and to gain insights toward better antibody testing.

Adult T-cell leukemia/lymphoma (ATL) occurs in approximately 5% of individuals infected with human T-cell leukemia virus type 1 (HTLV-1). A high proviral load (PVL; more than four copies per 100 peripheral blood mononuclear cells (PBMCs) or 1.6 copies per 100 blood leukocytes) and being male are risk factors for ATL development.

An All-Recombinant Protein-Based Culture System Specifically Identifies Hematopoietic Stem Cell Maintenance Factors.

Hematopoietic stem cells (HSCs) are considered one of the most promising therapeutic targets for the treatment of various blood disorders. However, due to difficulties in establishing stable maintenance and expansion of HSCs in vitro, their insufficient supply is a major constraint to transplantation studies. To solve these problems we have developed a fully defined, all-recombinant protein-based culture system.