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Table 1 Evidence for, and against, circulating progenitor cell generation of non-hematopoietic lung cell types.

From: Stem cells and repair of lung injuries

Study Type

Disease or Model

Tissue of Origin

Lung Cell Type Formed / Frequency

Method of Detection

Ref.

Animal, in-vivo

BMT

MSC

Undefined mesenchymal cells / occasional

PCR for collagen gene marker

[30]

Animal, in-vivo

Bleomycin fibrosis

MSC

Type I pneumocytes / rare

β galactosidase protein

[23]

Animal, in-vivo

BMT

HSC enrichment

Type II pneumocytes / up to 20%, bronchial epithelium / 4%

Y chromosome FISH, surfactant B mRNA

[31]

Animal, in-vivo

Radiation pneumonitis

Whole bone marrow

Type II pneumocytes, bronchial epithelium / up to 20% of type II cells

Y chromosome FISH, surfactant B mRNA

[25]

Animal, in-vivo

BMT

Whole bone marrow/EGFP retrovirus

Type II pneumocytes / 1–7%

EGFP, keratin immunostain, surfactant protein B FISH

[33]

Animal, in-vivo

BMT and parabiotic animals

HSC

Hematopoietic chimerism but exceedingly rare lung cell types

EGFP

[32]

Animal, in-vivo

Bleomycin fibrosis

MSC

Type II pneumocytes / ~1%

Y chromosome FISH

[22]

Animal, in-vivo

Radiation fibrosis

MSC or whole bone marrow

Fibroblasts / common

EGFP, Y chromosome FISH, vimentin immunostain

[26]

Animal, in-vivo

BMT

Bone marrow, EGFP labeled

Fibroblasts, Type I pneumocyte / occasional to rare

Flow cytometry

[34]

Animal, in-vitro and in-vivo

Hypoxia-induced pulmonary hypertension

Circulating BM-derived c-kit positive

c-kit positive cells in pulmonary artery vessel wall; In hypoxia, circulating cells generate endothelial and smooth muscle cells in-vitro

Flow cytometry and immunohistochemistry

[27]

Animal, in-vivo

Ablative radiation and elastase induced emphysema

GFP + fetal liver

Alveolar epithelium and endothelium; frequency not reported but increased by G-CSF and retinoic acid

Immunohistochemistry for CD45-, GFP+ cells

[28]

Animal, in-vivo

Bleomycin fibrosis

Whole marrow GFP+

GFP+ type I collagen expressing

Flow cytometry and immunohistochemistry, RT-PCR

[24]

Human, in-vitro

Heat shock in cell culture

MSC and SAEC

Cell fusion / common

Immunostaining, microarray

[39]

Animal, in-vivo

Human, in-vivo

OVA-sensitized mouse model

Allergen – sensitized asthmatics

CD34 positive, collagen I expressing fibrocytes

CD34 positive, collagen I expressing fibrocytes

Myofibroblasts / ?

Myofibroblasts / ?

CD34-positive, collagen I, α-smooth muscle actin

CD34-positive, collagen I, α-smooth muscle actin

[29]

Human, in-vivo

Human heart and lung transplant

Sex-mismatched donor lung or heart

No lung cell types of recipient origin

X and Y chromosome FISH, antibody stain for hematopoeitic cells

[36]

Human, in-vivo

Human lung transplant

Human BMT

Sex-mismatched donor lung

Sex-mismatched donor bone marrow

Bronchial epithelium, type II pneumocytes, glands of recipient origin / 9 – 24%

No lung cell types of donor origin

Y chromosome FISH, short tandem repeat PCR

Y chromosome FISH, short tandem repeat PCR

[35]

Human, in-vivo

Human BMT

Sex-mismatched donor bone marrow

Lung epithelium and endothelium of donor origin / up to 43%

X and Y chromosome FISH, keratin and PECAM immunostain

[38]

Human, in-vivo

Human BMT

Sex-mismatched donor bone marrow

No nasal epithelium of donor origin

Y chromosome FISH, cytokeratin immunostain

[37]

  1. BMT = bone marrow transplant (with prior ablation), MSC = mesenchymal stem cells (bone marrow stromal cells, adherent bone marrow cells), EGFP = enhanced green fluorescent protein, HSC = hematopoietic stem cells, FISH = fluoresence in situ hybridization, SAEC = small airway epithelial cells