Angiotensin-converting enzyme (CD143) specifies emerging lympho-hematopoietic progenitors in the human embryo.

Adult-type lympho-myeloid hematopoietic progenitors are first generated in the aorta-gonad-mesonephros region between days 27 and 40 of human embryonic development, but an elusive blood forming potential is present earlier in the underlying splanchnopleura. In the present study, we show that angiotensin-converting enzyme (ACE, also known as CD143), a recently identified cell-surface marker of adult human hematopoietic stem cells, is already expressed in all presumptive and developing blood-forming tissues of the human embryo and fetus: para-aortic splanchnopleura, yolk sac, aorta-gonad-mesonephros, liver, and bone marrow (BM). Fetal liver and BM-derived CD34(+)ACE(+) cells, but not CD34(+)ACE(-) cells, are endowed with long-term culture-initiating cell potential and sustain multilineage hematopoietic cell engraftment when transplanted into NOD/SCID mice.

Primary inflammation in human cystic fibrosis small airways.

Most cystic fibrosis (CF) patients die of lung failure, due to the combined effects of bacterial infection, neutrophil-mediated inflammation, and airway obstruction by hyperviscous mucus. To this day, it remains unclear where and how this pathological vicious circle is initiated in vivo. In particular, it has proven difficult to investigate whether inflammatory pathways are dysregulated in CF airways independently of infection.

Ex vivo development of functional human lymph node and bronchus-associated lymphoid tissue.

We introduce a novel in vivo model of human mucosal immunity, based on the implantation of human fetal bronchial mucosa and autologous peribronchial lymph node (PLN) in the severe combined immunodeficiency (SCID) mouse. In the SCID host, human fetal bronchi implanted alone retain macrophages and mast cells but lose T cells. In contrast, fetal bronchi co-implanted with PLN contain, in addition to macrophages and mast cells, numerous T cells and B cells, often clustered in intramucosal bronchus-associated lymphoid tissue (BALT).

Epithelial stem cell-mediated development of the human respiratory mucosa in SCID mice.

We have developed an in vivo assay for progenitor cells of the human tracheobronchial epithelium relying on the transplantation of human prenatal respiratory tissues into severe combined immunodeficiency mice. Engrafted embryonic or fetal open tracheobronchial rudiments are rapidly closed at each end by a neoformed membrane that we named the operculum. After 2-4 weeks, differentiated human respiratory epithelium covers both the native airway matrix and the new operculum.

Optimised retroviral infection of human epidermal keratinocytes: long-term expression of transduced integrin gene following grafting on to SCID mice.

Previous attempts to achieve long-term gene expression in retrovirally transduced human epidermal keratinocytes in vivo have been largely unsuccessful. This has been variously attributed to a failure to target epidermal stem cells, suboptimal grafting conditions or inactivation of the retroviral vector. In an attempt to overcome these problems we expressed the chick beta 1 integrin subunit in primary human epidermal keratinocytes, which allowed us to monitor retroviral gene expression on a cell-by-cell basis.