Hematopoietic stem cells (HSCs) play a crucial role in the generation of the body's blood and immune cells. This process takes place primarily in the bone marrow in specialized 'niche' microenvironments, which provide signals responsible for maintaining a balance between HSC quiescence, self-renewal, and lineage specification required for life-long hematopoiesis. While our understanding of these signaling mechanisms continues to improve, our ability to engineer them in vitro for the expansion of clinically relevant HSC populations is still lacking. In this review, we focus on development of biomaterials-based culture platforms for in vitro study of interactions between HSCs and their local microenvironment. The tools and techniques used for both examining HSC-niche interactions as well as applying these findings towards controlled HSC expansion or directed differentiation in 2D and 3D platforms are discussed. These novel techniques hold the potential to push the existing boundaries of HSC cultures towards high-throughput, real-time, and single-cell level biomimetic approaches that enable a more nuanced understanding of HSC regulation and function. Their application in conjunction with innovative biomaterial platforms can pave the way for engineering artificial bone marrow niches for clinical applications as well as elucidating the pathology of blood-related cancers and disorders.
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http://dx.doi.org/10.1002/biot.201400758 | DOI Listing |
Stem Cell Rev Rep
January 2025
Institute for Cellular and Molecular Medicine, Department of Immunology, SAMRC Extramural Unit for Stem Cell Research and Therapy, University of Pretoria, Pretoria, 0084, South Africa.
J Mol Med (Berl)
January 2025
Department of Hematology and Oncology, Children's Hospital of Nanjing Medical University, 72 Guangzhou Road, Nanjing, 210008, Jiangsu Province, China.
Glucose phosphate isomerase (GPI) deficiency caused by GPI gene mutations is a rare heterogenous condition that causes hereditary non-spherocytic hemolytic anemia (HNSHA). Patients who suffer from severe anemia may need more effective treatment. Here, clinical data and genetic testing results of two cases of HNSHA with GPI mutations treated with allogeneic hematopoietic stem cell transplantation (allo-HSCT) were retrospectively analyzed.
View Article and Find Full Text PDFAnn Hematol
January 2025
Hematology and Hematopoietic Stem Cell Transplant Center, Department of Medicine and Surgery, University of Naples Federico II, Via S. Pansini 5, Naples, 80131, Italy.
Splenomegaly is a quite common clinical feature of Philadelphia (Ph) negative chronic myeloproliferative neoplasms (MPNs) and its presence may, in some cases, drives treatment decision. Most importantly, palpable splenomegaly is a minor criterion for both pre-fibrotic/early primary myelofibrosis and primary myelofibrosis (PMF) diagnosis, even if clinical assessment by physical examination is poorly reliable and accurate. On the other hand, despite the International Working Group-Myeloproliferative Neoplasms Research and Treatment and European LeukemiaNet guidelines defined spleen response criteria by palpation, they also recognized the highly subjective nature of spleen size assessment by physical examination, and recommended objective confirmation of volume reduction via computed tomography or magnetic resonance imaging (MRI).
View Article and Find Full Text PDFJ Exp Med
March 2025
Department of Hematology, The Second Affiliated Hospital of Chongqing Medical University, School of Basic Medical Sciences, Chongqing Medical University, Chongqing, China.
Hematopoietic stem cells (HSCs) are susceptible to replication stress, which is a major contributor to HSC defects in Fanconi anemia (FA). Here, we report that HSCs relax the global chromatin by downregulating the expression of a chromatin architectural protein, DEK, in response to replication stress. DEK is abnormally accumulated in bone marrow (BM) CD34+ cells from patients with FA and in Fancd2-deficient HSCs.
View Article and Find Full Text PDFFront Oncol
January 2025
Department of Medical Oncology and Hematology, University of Zurich and University Hospital Zurich, Zurich, Switzerland.
Introduction: -rearrangements define a subclass of acute leukemias characterized by a distinct gene expression signature linked to the dysfunctional oncogenic fusion proteins arising from various chromosomal translocations involving the (also known as ) gene. Research on the disease pathomechanism in -rearranged acute leukemias has mainly focused on the upregulation of the stemness-related genes of the -family and their co-factor .
Results: Here we report the and fusion gene-dependent downregulation of , a TGF-β signaling axis transcription factor.
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