Several studies have suggested that the cyclin-dependent kinase (CDK) inhibitor p21 plays a crucial role in regulating hematopoietic stem and progenitor pool size. To allow assessment of long-term stem cell functioning in vivo, we have backcrossed a p21 null allele to C57BL/6 (B6) mice, the most commonly used mouse strain in hematopoietic stem cell research. In various in vitro assays, the homozygous deletion of the p21 allele did not affect the number of hematopoietic cells in B6 mice. Furthermore, the competitive repopulation ability was not different between p21-deficient and wild-type stem cells from both young and aged (20-month-old) mice. These results show that p21 is not essential for regulation of stem cell number in steady state. When proliferative stress was applied on p21-deficient stem cells by serial transplantation of 1,500 Lin(-)Sca-1(+)c-kit(+) (LSK) cells, again no detrimental effect was observed on cobblestone area-forming cell (CAFC) frequency and competitive repopulating ability. However, when bone marrow cells from mice that received 2 Gy of irradiation were transplanted, p21 deficiency resulted in a more than fourfold reduction in competitive repopulation index. Finally, we did not find major differences in cell cycle status and global gene expression patterns between LSK cells from p21-deficient and wild-type mice. Our findings indicate that the background of mice used for studying the function of a gene by genetic modification may determine the outcome. Cumulatively, our data fail to support the notion that p21 is essential for stem cell function during steady-state hematopoiesis, but may be relatively more important under conditions of cellular stress.
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http://dx.doi.org/10.1634/stemcells.2006-0631 | DOI Listing |
ACS Biomater Sci Eng
January 2025
Department of Gastrointestinal Surgery, Affiliated Hospital of Nantong University, Medical School of Nantong University, Nantong 226001, China.
Perianal fistulas (PAFs) are a severe complication of Crohn's disease that significantly impact patient prognosis and quality of life. While stem-cell-based strategies have been widely applied for PAF treatment, their efficacy remains limited. Our study introduces an injectable, temperature-controlled decellularized adipose tissue-alginate hydrogel loaded with dental pulp mesenchymal stem cells (DPMSCs) for in vivo fistula treatment.
View Article and Find Full Text PDFPLoS Genet
January 2025
Department of Veterinary Biosciences, Faculty of Veterinary Medicine, University of Helsinki, Helsinki, Finland.
Inositol 1,4,5-trisphosphate receptors (IP3R) mediate Ca2+ release from intracellular stores, contributing to complex regulation of numerous physiological responses. The involvement of the three IP3R genes (ITPR1, ITPR2 and ITPR3) in inherited human diseases has started to shed light on the essential roles of each receptor in different human tissues and cell types. Variants in the ITPR3 gene, which encodes IP3R3, have recently been found to cause demyelinating sensorimotor Charcot-Marie-Tooth neuropathy type 1J (CMT1J).
View Article and Find Full Text PDFPLoS One
January 2025
Department of Regenerative Medicine, Cell Science Research Center, Royan Institute for Stem Cell Biology and Technology, ACECR, Tehran, Iran.
Exosomes are natural membrane-enclosed nanovesicles (30-150 nm) involved in cell-cell communication. Recently, they have garnered considerable interest as nanocarriers for the controlled transfer of therapeutic agents to cells. Here, exosomes were derived from bone marrow mesenchymal stem cells using three different isolation methods.
View Article and Find Full Text PDFPLoS One
January 2025
Department of Orthopaedic Surgery, The Second Affiliated Hospital of Zunyi Medical University, Zunyi, Honghuagang District, Guizhou, China.
With the rise of bone tissue engineering (BET), 3D-printed HA/PCL scaffolds for bone defect repair have been extensively studied. However, little research has been conducted on the differences in osteogenic induction and regulation of macrophage (MPs) polarisation properties of HA/PCL scaffolds with different fibre orientations. Here, we applied 3D printing technology to prepare three sets of HA/PCL scaffolds with different fibre orientations (0-90, 0-90-135, and 0-90-45) to study the differences in physicochemical properties and to investigate the response effects of MPs and bone marrow mesenchymal stem cells (BMSCs) on scaffolds with different fibre orientations.
View Article and Find Full Text PDFAdv Sci (Weinh)
January 2025
Institute for Regenerative Medicine, State Key Laboratory of Cardiology and Medical Innovation Center, Shanghai East Hospital, School of Life Sciences and Technology, Tongji University, Shanghai, 200123, P. R. China.
Human amniotic epithelial cells (hAECs) have shown excellent efficacy in clinical research and have prospective applications in the treatment of many diseases. However, the properties of the hAECs and their proliferative mechanisms remain unclear. Here, single-cell RNA sequencing (scRNA-seq) is performed on hAECs obtained from amniotic tissues at different gestational ages and passages during in vitro culture.
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