The bone marrow leaves its scar: new concepts in pulmonary fibrosis

Abstract

Excess collagen deposition occurs in pulmonary fibrosis. A new study suggests that collagen overproduction may originate from cells derived from bone marrow precursors rather than parenchymal lung fibroblasts.

Figure 1

Origin of fibroblastic foci. Fibroblastic foci, sites of active collagen synthesis, are the pathologic hallmark of pulmonary fibrosis. The traditional view is that cytokine secretion by epithelial and inflammatory cells induces parenchymal lung fibroblasts to overproduce collagen and to differentiate into myofibroblasts. Several recent studies indicate that bone marrow–derived cells can engraft into lung tissue and produce collagen. Bone marrow–derived cells may be recruited to the lung by chemokines generated by macrophages.

Figure 2

Bone marrow cell populations. (a) Cross section of tubular bone showing the structure of bone marrow. Hematopoietic spaces are organized into cords by stromal cells (green lines) and contain distinct foci of developing erythroid and granulocytic cells interspersed among immature hematopoietic precursors. Mature blood cells enter the circulation by migrating across the marrow sinus endothelium. (b) Two populations of stem cells may be isolated from bone marrow. Mesenchymal stem cells, isolated from marrow stroma, adhere to tissue culture plasticware and have been shown to have the potential to differentiate into osteoblasts, adipocytes, and chondrocytes. Hematopoietic stem cells, which do not adhere to tissue culture plasticware, not only have the capacity to produce mature blood cells but also have been shown to engraft into liver, lung, kidney, heart, skeletal muscle, pancreas, and gastrointestinal tract. Fibrocytes, defined by the cell surface expression of collagen I, CD11b, CD13, CD34, CD45RO, MHC class II, and CD86, express the same chemokine receptors, CXCR4 and CCR7, as the collagen I–positive, GFP-positive cells in bleomycin-induced fibrotic lesions.