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Query: UNIPROT:P10721 (
c-kit
)
6,575
document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)
Recent studies suggest that bone marrow (BM)-derived stem cells have therapeutic efficacy in neonatal
hyperoxia
-induced lung injury (HILI).
c-kit
, a tyrosine kinase receptor that regulates angiogenesis, is expressed on several populations of BM-derived cells. Preterm infants exposed to
hyperoxia
have decreased lung angiogenesis. Here we tested the hypothesis that administration of BM-derived
c-kit
(+) cells would improve angiogenesis in neonatal rats with HILI. To determine whether intratracheal (IT) administration of BM-derived
c-kit
(+) cells attenuates neonatal HILI, rat pups exposed to either normobaric normoxia (21% O2) or
hyperoxia
(90% O2) from postnatal day (P) 2 to P15 were randomly assigned to receive either IT BM-derived green fluorescent protein (GFP)(+)
c-kit
(-) cells (PL) or BM-derived GFP(+)
c-kit
(+) cells on P8. The effect of cell therapy on lung angiogenesis, alveolarization, pulmonary hypertension, vascular remodeling, cell proliferation, and apoptosis was determined at P15. Cell engraftment was determined by GFP immunostaining. Compared to PL, the IT administration of BM-derived
c-kit
(+) cells to neonatal rodents with HILI improved alveolarization as evidenced by increased lung septation and decreased mean linear intercept. This was accompanied by an increase in lung vascular density, a decrease in lung apoptosis, and an increase in the secretion of proangiogenic factors. There was no difference in pulmonary vascular remodeling or the degree of pulmonary hypertension. Confocal microscopy demonstrated that 1% of total lung cells were GFP(+) cells. IT administration of BM-derived
c-kit
(+) cells improves lung alveolarization and angiogenesis in neonatal HILI, and this may be secondary to an improvement in the lung angiogenic milieu.
...
PMID:Bone marrow-derived c-kit+ cells attenuate neonatal hyperoxia-induced lung injury. 2375 97
Cardiac stem cells reside in niches where the oxygen levels are close to 3%. For cytotherapy, cells are conventionally expanded in ambient oxygen (21% O
2
) which represents
hyperoxia
compared to the oxygen tension of niches. Cardiosphere-derived cells (CDCs) are then transplanted to host tissue with lower-O
2
levels. The high-O
2
gradient can reduce the efficacy of cultured cells. Based on the assumption that minimizing injury due to O
2
gradients will enhance the yield of functionally efficient cells, CDCs were cultured in 3% O
2
and compared with cells maintained in ambient O
2
. CDCs were isolated from human right atrial explants and expanded in parallel in 21 and 3% oxygen and compared with regard to survival, proliferation, and retention of stemness. Increased cell viability even in the tenth passage and enhanced cardiosphere formation was observed in cells expanded in 3% O
2
. The cell yield from seven passages was fourfold higher for cells cultured in 3% O
2
. Preservation of stemness in hypoxic environment was evident from the proportion of
c-kit
-positive cells and reduced myogenic differentiation. Hypoxia promoted angiogenesis and reduced the tendency to differentiate to noncardiac lineages (adipocytes and osteocytes). Mimicking the microenvironment at transplantation, when shifted to 5% O
2
, viability and proliferation rate were significantly higher for CDCs expanded in 3% O
2
. Expansion of CDCs, from atria in sub-physiological oxygen, helps in obtaining a higher yield of healthy cells with better preservation of stem cell characteristics. The cells so cultured are expected to improve engraftment and facilitate myocardial regeneration.
...
PMID:Sub-physiological oxygen levels optimal for growth and survival of human atrial cardiac stem cells. 2838 45
Rationale:
Disruption of alveologenesis is associated with severe pediatric lung disorders, including bronchopulmonary dysplasia (BPD). Although c-KIT
+
endothelial cell (EC) progenitors are abundant in embryonic and neonatal lungs, their role in alveolar septation and the therapeutic potential of these cells remain unknown.
Objectives:
To determine whether c-KIT
+
EC progenitors stimulate alveologenesis in the neonatal lung.
Methods:
We used single-cell RNA sequencing of neonatal human and mouse lung tissues, immunostaining, and FACS analysis to identify transcriptional and signaling networks shared by human and mouse pulmonary c-KIT
+
EC progenitors. A mouse model of perinatal
hyperoxia
-induced lung injury was used to identify molecular mechanisms that are critical for the survival, proliferation, and engraftment of c-KIT
+
EC progenitors in the neonatal lung.
Measurements and Main Results:
Pulmonary c-KIT
+
EC progenitors expressing PECAM-1, CD34, VE-Cadherin, FLK1, and TIE2 lacked mature arterial, venal, and lymphatic cell-surface markers. The transcriptomic signature of c-KIT
+
ECs was conserved in mouse and human lungs and enriched in FOXF1-regulated transcriptional targets. Expression of FOXF1 and c-KIT was decreased in the lungs of infants with BPD. In the mouse, neonatal
hyperoxia
decreased the number of c-KIT
+
EC progenitors. Haploinsufficiency or endothelial-specific deletion of
Foxf1
in mice increased apoptosis and decreased proliferation of c-KIT
+
ECs. Inactivation of either
Foxf1
or
c-Kit
caused alveolar simplification. Adoptive transfer of c-KIT
+
ECs into the neonatal circulation increased lung angiogenesis and prevented alveolar simplification in neonatal mice exposed to
hyperoxia
.
Conclusions:
Cell therapy involving c-KIT
+
EC progenitors can be beneficial for the treatment of BPD.
...
PMID:Postnatal Alveologenesis Depends on FOXF1 Signaling in c-KIT
+
Endothelial Progenitor Cells. 3134 12
