Three-Dimensional Arrangement of Human Bone Marrow Microvessels Revealed by Immunohistology in Undecalcified Sections

Steiniger, Birte; Stachniss, Vitus; Wilhelmi, Verena; Seiler, Anja; Lampp, Katrin; Neff, Andreas; Guthe, Michael; Lobachev, Oleg

doi:10.1371/journal.pone.0168173

Cited by 10 publications

(20 citation statements)

References 39 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…A different spatial arrangement of capillaries and sinuses networks in human iliac crest respect to the mouse femora has been hypothesized ( Chen et al, 2017 ). This suggests that, together with the plausible inter-species variability, the different ossification pathway could be relevant ( Steiniger et al, 2016 ). Steiniger et al (2016) studied the arrangement of human BM micro-vessels applying 21 serial sections of about 1 cm 2 derived from a single human iliac crest specimen.…”

Section: Discussionmentioning

confidence: 99%

“…This suggests that, together with the plausible inter-species variability, the different ossification pathway could be relevant ( Steiniger et al, 2016 ). Steiniger et al (2016) studied the arrangement of human BM micro-vessels applying 21 serial sections of about 1 cm 2 derived from a single human iliac crest specimen. In this work, the distinction between sinusoids and capillaries was based on the inner caliber and expression of CD141 and CD34, where small CD34 + CD141 neg vessels were described as capillaries; consequently, perivascular cells were not investigated.…”

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

High NESTIN Expression Marks the Endosteal Capillary Network in Human Bone Marrow

Panvini

Pacini

Montali

et al. 2020

Front. Cell Dev. Biol.

View full text Add to dashboard Cite

Hematopoiesis is hosted, supported and regulated by a special bone marrow (BM) microenvironment known as “niche.” BM niches have been classified based on micro-anatomic distance from the bone surface into “endosteal” and “central” niches. Whilst different blood vessels have been found in both BM niches in mice, our knowledge of the human BM architecture is much more limited. Here, we have used a combination of markers including NESTIN, CD146, and αSMA labeling different blood vessels in benign human BM. Applying immunohistochemical/immunofluorescence techniques on BM trephines and performing image analysis on almost 300 microphotographs, we detected high NESTIN expression in BM endothelial cells (BMECs) of small arteries (A) and endosteal arterioles (EA), and also in very small vessels we named NESTIN+ capillary-like tubes (NCLTs), not surrounded by sub-endothelial perivascular cells that occasionally reported low levels of NESTIN expression. Statistically, NCLTs were detected within 40 μm from bone trabecula, frequently found in direct contact to the bone line and spatially correlated with hematopoietic stem/progenitor cells. Our results support the expression of NESTIN in human BMECs of EA and A in accordance with the updated classification of murine BM micro-vessels. NCLTs for their peculiar characteristics and micro-anatomical localization have been here proposed as transitional vessels possibly involved in regulating human hematopoiesis.

show abstract

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

High NESTIN Expression Marks the Endosteal Capillary Network in Human Bone Marrow

Panvini

Pacini

Montali

et al. 2020

Front. Cell Dev. Biol.

View full text Add to dashboard Cite

show abstract

“…While it is possible to trace a single entity through a series, gaining a full 3D perception is impossible without a full-fledged 3D reconstruction. An inspection of our reconstructions in VR (Steiniger et al, 2018a(Steiniger et al, ,b, 2021 was much faster than a typical inspection of 3D data without VR (Steiniger et al, 2016), as section 6 details.…”

Section: Why Non-vr Tools Do Not Sufficementioning

confidence: 98%

“…The healing of damaged regions (Lobachev, 2020) is an optional step. The step "mesh coloring" involves, e. g., coloring of selected components (Steiniger et al, 2018a(Steiniger et al, ,b, 2021 or visualization of shape diameter function (Steiniger et al, 2016). QC is used as initial visual analytics.…”

Section: A 3d Reconstruction Pipeline For Serial Sectionsmentioning

confidence: 99%

Inspection of Histological 3D Reconstructions in Virtual Reality

Lobachev¹,

Berthold²,

Pfeffer³

et al. 2021

Front. Virtual Real.

Self Cite

View full text Add to dashboard Cite

3D reconstruction is a challenging current topic in medical research. We perform 3D reconstructions from serial sections stained by immunohistological methods. This paper presents an immersive visualization solution to quality control (QC), inspect, and analyze such reconstructions. QC is essential to establish correct digital processing methodologies. Visual analytics, such as annotation placement, mesh painting, and classification utility, facilitates medical research insights. We propose a visualization in virtual reality (VR) for these purposes. In this manner, we advance the microanatomical research of human bone marrow and spleen. Both 3D reconstructions and original data are available in VR. Data inspection is streamlined by subtle implementation details and general immersion in VR.

show abstract

“…In animals, sinusoids occupy 3-6 times as much BM area as the arterial part of the circulation, and they are unique for the hematopoietic BM [21]. The importance of sinusoids for hematopoietic BM function is substantiated by observations in humans, showing that the microvascular bed of the hematopoietic BM consists mainly of sinusoids, while that of hematopoietic-inactive BM adipose tissue consists mainly of capillaries [22]. Moreover, because increased oxygen tension leads to HSC differentiation [23], it is important to acknowledge that sinusoids represent the venous part of the BM circulation.…”

Section: Introductionmentioning

confidence: 99%

Human hematopoietic microenvironments

Kristensen

Andersen

Patriarca³

et al. 2021

PLoS ONE

View full text Add to dashboard Cite

Dormancy of hematopoietic stem cells and formation of progenitors are directed by signals that come from the bone marrow microenvironment. Considerable knowledge has been gained on the murine hematopoietic stem cell microenvironment, while less so on the murine progenitor microenvironment and even less so on these microenvironments in humans. Characterization of these microenvironments is decisive for understanding hematopoiesis and finding new treatment modalities against bone marrow malignancies in the clinic. However, it is equally challenging, because hematopoietic stem cells are difficult to detect in the complex bone marrow landscape. In the present study we are characterizing the human hematopoietic stem cell and progenitor microenvironment. We obtained three adjacent bone marrow sections from ten healthy volunteers. One was used to identify a population of CD34+/CD38- “hematopoietic stem cells and multipotent progenitors” and a population of CD34+/CD38+ “progenitors” based on immunofluorescence pattern/intensity and cellular morphology. The other two were immunostained respectively for CD34/CD56 and for CD34/SMA. Using the combined information we performed a non-computer-assisted quantification of nine bone marrow components (adipocytes, megakaryocytes, bone surfaces, four different vessel types (arteries, capillaries, sinusoids and collecting sinuses), other “hematopoietic stem cells and multipotent progenitors” and other “progenitors”) within 30 μm of “hematopoietic stem cells and multipotent progenitors”, “progenitors”, and “random cell profiles”. We show that the microenvironment of the “hematopoietic stem cells and multipotent progenitors” is significantly enriched in sinusoids and megakaryocytes, while the microenvironment of the “progenitors” is significantly enriched in capillaries, other “progenitors”, bone surfaces and arteries.

show abstract

Three-Dimensional Arrangement of Human Bone Marrow Microvessels Revealed by Immunohistology in Undecalcified Sections

Cited by 10 publications

References 39 publications

High NESTIN Expression Marks the Endosteal Capillary Network in Human Bone Marrow

High NESTIN Expression Marks the Endosteal Capillary Network in Human Bone Marrow

Inspection of Histological 3D Reconstructions in Virtual Reality

Human hematopoietic microenvironments

Contact Info

Product

Resources

About