Engraftment of Intraperitoneally Injected Bone Marrow Cells to Newborn Mice Injected with an Angiogenesis Inhibitor.

Cho,  Su Jin; Ju,  Sun Young; Woo,  So Youn; Kang,  Hyoung Jin; Ahn,  Hyo Seop; Ryu,  Kyung Ha; Park,  Eun Ae

Original Article

Journal of the Korean Society of Neonatology 2008;15(1):22-31.
Published online May 1, 2008.

Engraftment of Intraperitoneally Injected Bone Marrow Cells to Newborn Mice Injected with an Angiogenesis Inhibitor.

Su Jin Cho, Sun Young Ju, So Youn Woo, Hyoung Jin Kang, Hyo Seop Ahn, Kyung Ha Ryu, Eun Ae Park

¹Department of Pediatrics, Ewha Womans University School of Medicine, Seoul, Korea. ujin-cho@ewha.ac.kr
²Department of Microbiology, Ewha Womans University School of Medicine, Seoul, Korea.
³Department of Pediatrics, Seoul National University College of Medicine, Seoul, Korea.

혈관생성 억제제를 주사한 마우스 모델에서의 골수 세포의 복강 내 주입 후 생착

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Abstract

PURPOSE
Bronchopulmonary dysplasia (BPD) is characterized by arrested vascular and alveolar growth in the premature lung. Considering the consequences of arrested lung growth, the idea of administering bone marrow cells to enhance the inborn repair mechanism is promising as this may reduce the morbidity and mortality of BPD. We followed enhanced green fluorescent protein (EGFP)-labeled bone marrow cells (BMC) injected intraperitoneally into non-EGFP mice in order to determine their fate after transplantation.
METHODS
An angiogenesis inhibitor, SU1498, was injected subcutaneously on day 3 in non-EGFP C57BL/6 newborn mice to create a model of arrested alveolar development. On the following day, 1x10(6) BMCs isolated from major histocompatibility complex (MHC)- matched syngenic EGFP mice were injected intraperitoneally to non-EGFP BPD mice. Morphometric analysis, immunostaining, and confocal microscopy were performed to determine the fate of EGFP-positive stem cells in the injured lung.
RESULTS
SU1498 injection reduced alveolar surface area and mean alveolar volume in newborn mice. BMC injection resulted in recovery of lung structure comparable to controls. EGFP-positive BMCs were identified in the lungs of the recipient mice after intraperitoneal injection. The injected EGFP cells were co-stained with endothelial and epithelial cells of the developing lung as determined by confocal microscopy.
CONCLUSION
Our results illustrated that EGFP-positive BMCs engrafted and trans- differentiated into epithelial and endothelial cells after intraperitoneal injection in a mouse model of arrested alveolar development.

Key Words: Alveolarization; Bone marrow cell; Engraftment