Spatial gradients of blood vessels and hematopoietic stem and progenitor cells within the marrow cavities of the human skeleton

Abstract

This report evaluates the spatial profile of blood vessel fragments (BVFs) and CD34(+) and CD117(+) hematopoietic stem and progenitor cells (HSPCs) in human cancellous bone. Bone specimens were sectioned, immunostained (anti-CD34 and anti-CD117), and digitally imaged. Immunoreactive cells and vessels were then optically and morphometrically identified and labeled on the corresponding digital image. The distance of each BVF, or CD34(+) or CD117(+) HSPC to the nearest trabecular surface was measured and binned in 50-microm increments. The relative concentration of HSPCs and BVFs within cancellous marrow was observed to diminish with increasing distance in the marrow space. On average, 50% of the CD34(+) HSPC population, 60% of the CD117(+) HSPC population, and 72% of the BVFs were found within 100 microm of the bone surfaces. HSPCs were also found to exist in close proximity to BVFs, which supports the notion of a shared HSPC and vessel spatial niche.

Figure 1

Spatial gradients of blood vessel fragments and cell-to-vessel distance frequencies. Mean areal concentrations of CD34⁺ vessels in active bone marrow as a function of distance into the marrow cavities of (A) ribs, (B) L₁ vertebrae, and (C) iliac crest, and frequency distribution of distances separating pairs of hematopoietic cells and blood vessels within the marrow cavities of (D) ribs, (E) L₁ vertebrae, and (F) iliac crest. Dashed line represents an exponential or Lorentzian fit to the data with R² values shown. Also shown is the population mean average concentration (horizontal solid) ± 1σ (horizontal dashed).

Figure 2

Spatial gradients of CD34⁺ and CD117⁺ hematopoietic stem and progenitor cells in bone marrow. Mean areal concentrations of hematopoietic cells in active bone marrow as a function of distance into the marrow cavities of (A) ribs (CD34⁺), (B) L₁ vertebrae (CD34⁺), (C) iliac crest (CD34⁺), (D) ribs (CD117⁺), (E) L₁ vertebrae (CD117⁺), and (F) iliac crest (CD117⁺). Data points indicate specimen-averaged mean values binned every 50 μm, whereas the dashed line represents a logarithmic or linear fit to the data with R² values shown. Also shown is the population mean average concentration (horizontal solid) ± 1σ (horizontal dashed).