A. Hematopoietic Stroma and Microenvironment

2015 ◽  
pp. 210-292
Author(s):  
F. D. Wilson
Keyword(s):  
Hematopoietic Stroma

scholarly journals Monocytes, Macrophages, and Their Potential Niches in Synovial Joints – Therapeutic Targets in Post-Traumatic Osteoarthritis?

2021 ◽  
Vol 12 ◽  
Author(s):  
Patrick Haubruck ◽  
Marlene Magalhaes Pinto ◽  
Babak Moradi ◽  
Christopher B. Little ◽  
Rebecca Gentek
Keyword(s):  
Synovial Fibroblasts ◽  
Cellular Interactions ◽  
Joint Injury ◽  
Synovial Joints ◽  
Joint Disorder ◽  
Hematopoietic Stroma ◽  
Post Traumatic ◽  
Micro Anatomy ◽  
Molecular Signals ◽  
Potential Interactions

Synovial joints are complex structures that enable normal locomotion. Following injury, they undergo a series of changes, including a prevalent inflammatory response. This increases the risk for development of osteoarthritis (OA), the most common joint disorder. In healthy joints, macrophages are the predominant immune cells. They regulate bone turnover, constantly scavenge debris from the joint cavity and, together with synovial fibroblasts, form a protective barrier. Macrophages thus work in concert with the non-hematopoietic stroma. In turn, the stroma provides a scaffold as well as molecular signals for macrophage survival and functional imprinting: “a macrophage niche”. These intricate cellular interactions are susceptible to perturbations like those induced by joint injury. With this review, we explore how the concepts of local tissue niches apply to synovial joints. We introduce the joint micro-anatomy and cellular players, and discuss their potential interactions in healthy joints, with an emphasis on molecular cues underlying their crosstalk and relevance to joint functionality. We then consider how these interactions are perturbed by joint injury and how they may contribute to OA pathogenesis. We conclude by discussing how understanding these changes might help identify novel therapeutic avenues with the potential of restoring joint function and reducing post-traumatic OA risk.

The In Vitro Infection of the Hematopoietic Stroma of Trout Kidney by Hemorrhagic Septicemia Rhabdovirus

1993 ◽  
Vol 6 (3) ◽  
pp. 185-191 ◽  
Author(s):  
M.L. DIAGO ◽  
A. ESTEPA ◽  
P. LÓPEZ-FIERRO ◽  
A. VILLENA ◽  
J.M. COLL
Keyword(s):  
Hematopoietic Stroma

Effect of the thymus on precursor cells of the hematopoietic stroma

1979 ◽  
Vol 87 (6) ◽  
pp. 617-619
Author(s):  
T. V. Todriya ◽  
O. A. Gurevich ◽  
I. L. Chertkov
Keyword(s):  
Precursor Cells ◽  
Hematopoietic Stroma

Early Growth Response (EGR)-1 Expression Regulates Colony Forming Capacity and Hematopoietic Support Function in Human Primary Bone Marrow Stromal Stem Cells

Blood ◽  
2016 ◽  
Vol 128 (22) ◽  
pp. 3886-3886
Author(s):  
Hongzhe Li ◽  
Roshanak Ghazanfari ◽  
Dimitra Zacharaki ◽  
Hooi Ching Lim ◽  
Stefan Scheding
Keyword(s):  
Stem Cells ◽  
Bone Marrow ◽  
Stem Cell ◽  
Support Function ◽  
Bone Marrow Cells ◽  
Early Growth Response ◽  
Hematopoietic Stroma ◽  
Colony Forming Capacity ◽  
Stromal Stem Cells

Abstract Bone marrow stromal stem cells (BMSCs) are essential components of the hematopoietic environment. BMSCs play a key role in regulating hematopoiesis and, furthermore, as skeletal stem cells they give rise to osteoblasts, adipocytes, and chondrocytes. However, despite this important role of BMSCs in bone and bone marrow physiology, little is known about how proliferation, differentiation and hematopoietic support functions of BMSCs are regulated. We hypothesized that primary human BMSCs have a distinct transcriptional regulatory system, which control BMSC stem cell properties and biological functions. We have previously reported gene expression profiling of highly-enriched human primary BMSCs (Li et al, Stem Cell Reports, 3(6):965-74, 2014), which demonstrated a substantially higher expression of early growth response 1 (EGR1) in primary cells compared to the non-colony-forming cells and cultured stromal cells, respectively. EGR1 is a member of the immediate early response transcription factor family, which has a function in cell growth, development, and stress responses in many tissues. EGR1 has been previously reported to be important for hematopoietic stem cell (HSC) proliferation and localization (Min et al. Cell Stem Cell, 2(4):380-91, 2008), but its role in non-hematopoietic bone marrow cells has thus far not been investigated. Therefore, we aimed to study the possible role of EGR1 in stroma stem cell proliferation and hematopoietic supporting function. Our data demonstrate that the expression of EGR1 as measured by qPCR was 126 ± 9-fold higher in highly fibroblast colony-forming cells (CFU-F) enriched human primary linneg/CD45neg/CD271pos/CD140aneg bone marrow cells compared to the non-colony forming CD45neg/CD271neg cell population. Furthermore, EGR1 expression in CD271posCD140aneg cells was 3 ± 0.2 -fold higher than in the CD271posCD140apos cell population, which has only minimal CFU-F activity. EGR1 expression decreased dramatically during culture with a more than 30-fold difference between primary and passage one and six cells. Down-regulation of EGR1 expression by shRNA did not affect the multi-differentiation capacity (adipogenic, osteogenic) and surface marker expression profile of BMSCs in vitro compared to controls. However, colony-forming capacity and proliferation was considerably increased in EGR1 knockdown cells, i.e. shRNA- transduced stromal cells produced up to 1.8 ± 0.1-fold more CFU-F compared to controls, whereas CFU-F were virtually absent when assaying EGR1 overexpressing cells. Furthermore, population doubling times were decreased in EGR1 knockdown cells but significantly increased (2.4 ± 0.3-fold) in EGR1 overexpressing cells. These data indicate that EGR1 expression negatively regulates BMSC proliferation and colony-forming capacity. On the other hand, hematopoietic support function was decreased in EGR1 knockdown cells as measured by the production of transplantable CD34posCD90pos HSC in stroma co-culture experiments (4-day serum-free culture supplemented with SCF 25 ng/ml, TPO 25 ng/ml, and FLT3L 25 ng/ml, 1×104 CD34pos seeded cord blood cells). Here, the positive effect of the supporting stroma was neutralized by knockdown of EGR1. Numbers of CD34posCD90pos HSC produced in co-cultures with EGR1 knockdown stroma cells were as low as 1,053 ± 316 compared to 6,100 ± 840 in control co-cultures (scamble control). Without stroma, 840 ± 210 CD34posCD90pos cells were generated from 1×104 seeded CD34pos cells. Furthermore, expansion of CD34posCD90posCB cells was increased in co-cultures with EGR1 overexpressing cells, indicating that EGR1is a positive regulator of hematopoietic stroma support in human BMSC, and confirmatory in-vivo xenotransplantation studies are ongoing. In summary, EGR1 is highly expressed by primary BM-MSC compared with non-colony forming cells and is downregulated during culture. EGR1 expression negatively regulates BMSC proliferation and colony formation while positively regulating hematopoietic stroma support function. Our data thus indicate that EGR1 may act as an important BMSC regulator coordinating the specific functions of BMSC in their different biological contexts. Disclosures No relevant conflicts of interest to declare.

scholarly journals Some observations of the hematopoietic status in vivo and in vitro on mice of genotype S1/S1d

Blood ◽  
1976 ◽  
Vol 48 (4) ◽  
pp. 601-608 ◽  
Author(s):  
FD Wilson ◽  
L O'Grady
Keyword(s):  
Bone Marrow ◽  
Colony Growth ◽  
Hematopoietic Stem ◽  
Quantitative Studies ◽  
Bone Marrow Cultures ◽  
Marrow Stroma ◽  
Constant Cell ◽  
Hematopoietic Stroma

Abstract Studies on the mechanism of anemia in mice of genotype S1/S1d have implicated the hematopoietic stroma (the hematopoietic inductive microenvironment, HIM) rather than hematopoietic stem cells as the site of the defect. Using methylcellulose-supported bone marrow culture systems, we have observed, in addition to classical hematopoietic colonies, the formation of surface associated fibroblastic plaques that could stimulate hematopoietic colony growth. These plaques were hypothesized to be derived from bone marrow stroma precursors. In view of the reported stromal-based defect in S1/S1d mice, studies were initiated, using our culture system, to determine if abnormalities exist in the plaque-forming potentials of these mice. Relative to controls, bone marrow derived from S1/S1d mice exhibited a significant decrease in hematopoietic colonly-forming units in culture, but no differences were apparent in the absolute numbers of fibroblastic plaque-forming units or in the ability of such plaques once derived to stimulate hematopoietic colony growth when overlain with fresh normal bone marrow preparations. Quantitative studies on the bone marrow of the S1/S1d mice revealed a marked reduction in total nucleated cells per femur. The importance of evaluating the results of bone marrow cultures in an absolute (i.e., number of units per femur) rather than a relative (i.e., number of units forming in a constant cell inoculum) term was underlined by these studies.

Platelet-Derived Growth Factor Enhances Expansion of Umbilical Cord Blood CD34+ Cells in Contact with Hematopoietic Stroma

2005 ◽  
Vol 14 (2) ◽  
pp. 223-230 ◽  
Author(s):  
Rui Jun Su ◽  
Karen Li ◽  
Xiao Bing Zhang ◽  
Patrick Man Pan Yuen ◽  
Chi Kong Li ◽  
...  
Keyword(s):  
Growth Factor ◽  
Cord Blood ◽  
Umbilical Cord ◽  
Umbilical Cord Blood ◽  
Platelet Derived Growth Factor ◽  
Cd34 Cells ◽  
Cord Blood Cd34 ◽  
Hematopoietic Stroma

The Effects of Graded Doses of 1 MeV Fission Neutrons or X Rays on the Murine Hematopoietic Stroma

1992 ◽  
Vol 131 (3) ◽  
pp. 302 ◽  
Author(s):  
E. I. M. Meijne ◽  
R. E. Ploemacher ◽  
O. Vos ◽  
R. Huiskamp
Keyword(s):  
X Rays ◽  
Hematopoietic Stroma ◽  
Fission Neutrons

scholarly journals Dissecting human embryonic skeletal stem cell ontogeny by single-cell transcriptomic and functional analyses

Cell Research ◽  
2021 ◽  
Author(s):  
Jian He ◽  
Jing Yan ◽  
Jianfang Wang ◽  
Liangyu Zhao ◽  
Qian Xin ◽  
...  
Keyword(s):  
Single Cell ◽  
Progenitor Cells ◽  
Limb Bud ◽  
Cellular Heterogeneity ◽  
Transcriptional Networks ◽  
Marker Genes ◽  
Long Bones ◽  
Hematopoietic Stroma ◽  
Human Limb ◽  
Functional Analyses

AbstractHuman skeletal stem cells (SSCs) have been discovered in fetal and adult long bones. However, the spatiotemporal ontogeny of human embryonic SSCs during early skeletogenesis remains elusive. Here we map the transcriptional landscape of human limb buds and embryonic long bones at single-cell resolution to address this fundamental question. We found remarkable heterogeneity within human limb bud mesenchyme and epithelium, and aligned them along the proximal–distal and anterior–posterior axes using known marker genes. Osteo-chondrogenic progenitors first appeared in the core limb bud mesenchyme, which give rise to multiple populations of stem/progenitor cells in embryonic long bones undergoing endochondral ossification. Importantly, a perichondrial embryonic skeletal stem/progenitor cell (eSSPC) subset was identified, which could self-renew and generate the osteochondral lineage cells, but not adipocytes or hematopoietic stroma. eSSPCs are marked by the adhesion molecule CADM1 and highly enriched with FOXP1/2 transcriptional network. Interestingly, neural crest-derived cells with similar phenotypic markers and transcriptional networks were also found in the sagittal suture of human embryonic calvaria. Taken together, this study revealed the cellular heterogeneity and lineage hierarchy during human embryonic skeletogenesis, and identified distinct skeletal stem/progenitor cells that orchestrate endochondral and intramembranous ossification.

Lack of Recovery of Murine Hematopoietic Stromal Cells After Irradiation-induced Damage

Blood ◽  
1974 ◽  
Vol 44 (3) ◽  
pp. 385-392 ◽  
Author(s):  
W. Chamberlin ◽  
J. Barone ◽  
A. Kedo ◽  
W. Fried
Keyword(s):  
Stromal Cells ◽  
Contributing Factors ◽  
Colony Forming Units ◽  
X Irradiation ◽  
Hematopoietic Stroma

Abstract The rates of recovery of colony-forming units (CFU) and of hematopoietic stroma following x-irradiation were compared. Hematopoietic stromal function of femurs and spleens was assessed by assaying the number of CFU in those sites 6 wk after implanting them subcutaneously into isogeneic hosts. Whereas the number of CFU returned to preirradiation levels in 6 wk, the hematopoietic stroma did not recover significantly in 9 wk. The reasons for regeneration of CFU in a defective stroma were next investigated. Two contributing factors were identified: (1) Stromal damage following 950 rads is such as to retard the rate of regeneration of CFU without significantly limiting the eventual number of CFU in the site, and (2) Radiated mice contain factor(s), possibly humoral, which accelerate the rate of regeneration of CFU.

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