Bone marrow-derived c-kit+ cells attenuate neonatal hyperoxia-induced lung injury

Shalini Ramachandran, Cleide Suguihara, Shelley Drummond, Konstantinos Chatzistergos, Jammie Klim, Eneida Torres, Jian Huang, Dorothy Hehre, Claudia O. Rodrigues, Ian K. McNiece, Joshua M. Hare, Karen C. Young

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Abstract

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.

Original languageEnglish (US)
Pages (from-to)85-95
Number of pages11
JournalCell Transplantation
Volume24
Issue number1
DOIs
StatePublished - 2015

Fingerprint

Hyperoxia
Lung Injury
Bone
Bone Marrow
Lung
Green Fluorescent Proteins
Proteins
Cell death
Pulmonary Hypertension
Rats
Apoptosis
Confocal microscopy
Cell proliferation
Stem cells
Receptor Protein-Tyrosine Kinases
Cell- and Tissue-Based Therapy
Premature Infants
Confocal Microscopy
Bone Marrow Cells
Blood Vessels

Keywords

  • Angiogenesis
  • Bronchopulmonary dysplasia
  • C-kit
  • Hyperoxia
  • Stem cells

ASJC Scopus subject areas

  • Cell Biology
  • Transplantation
  • Biomedical Engineering

Cite this

Ramachandran, S., Suguihara, C., Drummond, S., Chatzistergos, K., Klim, J., Torres, E., ... Young, K. C. (2015). Bone marrow-derived c-kit+ cells attenuate neonatal hyperoxia-induced lung injury. Cell Transplantation, 24(1), 85-95. https://doi.org/10.3727/096368913X667736

Bone marrow-derived c-kit+ cells attenuate neonatal hyperoxia-induced lung injury. / Ramachandran, Shalini; Suguihara, Cleide; Drummond, Shelley; Chatzistergos, Konstantinos; Klim, Jammie; Torres, Eneida; Huang, Jian; Hehre, Dorothy; Rodrigues, Claudia O.; McNiece, Ian K.; Hare, Joshua M.; Young, Karen C.

In: Cell Transplantation, Vol. 24, No. 1, 2015, p. 85-95.

Research output: Contribution to journalArticle

Ramachandran, S, Suguihara, C, Drummond, S, Chatzistergos, K, Klim, J, Torres, E, Huang, J, Hehre, D, Rodrigues, CO, McNiece, IK, Hare, JM & Young, KC 2015, 'Bone marrow-derived c-kit+ cells attenuate neonatal hyperoxia-induced lung injury', Cell Transplantation, vol. 24, no. 1, pp. 85-95. https://doi.org/10.3727/096368913X667736
Ramachandran, Shalini ; Suguihara, Cleide ; Drummond, Shelley ; Chatzistergos, Konstantinos ; Klim, Jammie ; Torres, Eneida ; Huang, Jian ; Hehre, Dorothy ; Rodrigues, Claudia O. ; McNiece, Ian K. ; Hare, Joshua M. ; Young, Karen C. / Bone marrow-derived c-kit+ cells attenuate neonatal hyperoxia-induced lung injury. In: Cell Transplantation. 2015 ; Vol. 24, No. 1. pp. 85-95.
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abstract = "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.",
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